Infectious Diseases

To the Editor:

The increase in nontuberculous mycobacteria (NTM) infections over the last 3 decades likely is multifaceted, including increased clinical awareness, improved laboratory diagnostics, growing numbers of immunocompromised patients, and an aging population.^1,2 Historically, the majority of mycobacteria-related diseases are due to Mycobacterium tuberculosis, Mycobacterium bovis, and Mycobacterium leprae.³

Mycobacterium haemophilum is a slow-growing acid-fast bacillus (AFB) that differs from other Mycobacterium species in that it requires iron-supplemented media and incubation temperatures of 30°C to 32°C for culture. As these requirements for growth are not standard for AFB cultures, M haemophilum infection may be underrecognized and underreported.³Mycobacterium haemophilum infections largely are cutaneous and generally are seen in AIDS patients and bone marrow transplant recipients who are iatrogenically immunosuppressed.^4,5 No species-specific treatment guidelines exist²; however, triple-drug therapy combining a macrolide, rifamycin, and a quinolone for a minimum of 12 months often is recommended.

A 64-year-old man with a history of coronary artery disease, hypertension, hyperlipidemia, and acute myelogenous leukemia (AML) underwent allogenic stem cell transplantation. His posttransplant course was complicated by multiple deep vein thromboses, hypogammaglobulinemia, and graft-vs-host disease (GVHD) of the skin and gastrointestinal tract that manifested as chronic diarrhea, which was managed with chronic prednisone. Thirteen months after the transplant, the patient presented to his outpatient oncologist (M.K.) for evaluation of painless, nonpruritic, erythematous papules and nodules that had emerged on the right side of the chest, right arm, and left leg of approximately 2 weeks’ duration.

On review of systems by oncology, the patient denied any fevers, chills, or night sweats but noted chronic loose nonbloody stools without abdominal pain, likely related to the GVHD. The patient’s medications included prednisone 20 mg once daily, fluconazole, amitriptyline, atovaquone, budesonide, dabigatran, metoprolol, pantoprazole, rosuvastatin, senna glycoside, spironolactone, tramadol, and valacyclovir.

Physical examination revealed multiple singular erythematous nodules on the right side of the chest (Figure 1A), right arm (Figure 1B), and left leg. There was no regional lymphadenopathy. The patient was afebrile and hemodynamically stable. A biopsy of the arm performed to rule out leukemia cutis revealed a granulomatous dermatitis with numerous AFB (Figures 2A and 2B), which were confirmed on Ziehl-Neelsen staining (Figures 2C and 2D). The presence of AFB raised concern for a disseminated mycobacterial infection. The patient was admitted to our institution approximately 1 week after the outpatient biopsy was performed. He was evaluated by infectious diseases (B.H.) and was recommended for repeat biopsy with AFB culture and for initiation of intravenous antibiotics.

The patient was evaluated by the dermatology consultation service on hospital day 1. At the time of consultation, the lesions were still painless but had enlarged. Two new satellite lesions were noted on his other extremities. Due to the widespread distribution of the lesions, there was concern for disseminated disease. The relatively rapid onset of new lesions increased concern for infection with rapid-growing mycobacteria, including Mycobacterium abscessus, Mycobacterium fortuitum, and Mycobacterium chelonae. A detailed history revealed that the patient’s wife had a fish tank, which supported the inclusion of Mycobacterium marinum in the differential; however, further questioning revealed that the patient never came in contact with the aquarium water. The initial outpatient biopsy had not been sent for culture. Following inpatient biopsy, the patient was initiated on empiric antimycobacterials, including imipenem, amikacin, clarithromycin, and levofloxacin. Computed tomography of the head was negative for cerebral involvement.

Acid-fast bacilli blood cultures were drawn per the recommendation from infectious diseases in an attempt to confirm disseminated disease; however, blood cultures remained negative. Tissue biopsy from the right arm was sent for AFB staining and culture. Many AFB were identified on microscopy, and growth was observed in the mycobacterial growth indicator tube after 6 days of incubation. The DNA probe was negative for M tuberculosis complex or Mycobacterium avium complex.

The patient was discharged on hospital day 6 on empiric therapy for rapid-growing mycobacteria while cultures were pending. The empiric regimen included intravenous imipenem 1 g every 6 hours, intravenous amikacin 1 g once daily, clarithromycin 500 mg every 12 hours, and levofloxacin 750 mg once daily. All solid media cultures were negative at the time of discharge.

The biopsy specimen proved difficult to culture on solid media using traditional methods. Three weeks after the inpatient biopsy, the microbiology laboratory reported that growth was observed on solid media that was incubated at 30°C and supplemented with iron. These findings were not characteristic of a rapidly growing mycobacteria (eg, M fortuitum, M chelonae, M abscessus) or M marinum but raised concern for infectionwith M haemophilum. Antimycobacterial treatment was adjusted to amikacin, clarithromycin, levofloxacin, and rifabutin.

Six weeks after the inpatient skin biopsy, final speciation confirmed infection with M haemophilum. The isolate proved susceptible to amikacin (minimal inhibitory concentration [MIC], 16), clarithromycin (MIC, 0.12), linezolid (MIC, <1), moxifloxacin (MIC, 0.5), rifabutin (MIC, <0.25), and trimethoprim-sulfamethoxazole (MIC, 0.5/9.5). The isolate was resistant to ciprofloxacin (MIC, 4), ethambutol (MIC, >16), and rifampin (MIC, 2). Based on these findings, an infectious disease specialist modified the treatment regimen to azithromycin 600 mg once daily, moxifloxacin 400 mg once daily, and rifabutin 300 mg once daily. Azithromycin was substituted for clarithromycin in an attempt to minimize the gastrointestinal side effects of the antibiotics. The infectious disease specialist was concerned that the clarithromycin could exacerbate the patient’s chronic GVHD-associated diarrhea, which posed a challenge to the oncologist, who was attempting to manage the patient’s GVHD and minimize the use of additional prednisone. At the time of this change, the patient was doing well clinically and denied any active skin lesions.

Four months later, he developed new left-sided neck swelling. Computed tomography revealed nonspecific enhancement involving the skin and superficial subcutaneous tissues in the left anterior neck. He was referred to otolaryngology given concern for recurrent infection vs leukemia cutis. He underwent excisional biopsy. Pathology was negative for malignancy but demonstrated subcutaneous necrotizing granulomatous inflammation with a positive AFB stain. Tissue AFB cultures revealed moderate AFB on direct stain, but there was no AFB growth at 12 weeks. Clarithromycin was restarted in place of azithromycin to increase the potency of the antimycobacterial regimen. Cultures from this neck biopsy were negative after 12 weeks of incubation.

In addition to this change in antibiotic coverage, the patient’s medical oncologist tapered the patient’s immunosuppression considerably. The patient subsequently completed 12 months of therapy with clarithromycin, moxifloxacin, and rifabutin starting from the time of the neck biopsy. He remained free of recurrence of mycobacterial infection for nearly 2 years until he died from an unrelated illness.

Nontuberculous mycobacteria are an ubiquitous environmental group.² Sources include soil and natural water (M avium), fish tanks and swimming pools (M marinum), and tap water and occasionally domestic animals (Mycobacterium kansasii). Additionally, rapidly growing NTM such as M abscessus, M chelonae, and M fortuitum have been isolated from soil and natural water supplies.³

Mycobacterium haemophilum is a fastidious organism with a predilection for skin of the chest and extremities. Iatrogenically or inherently immunocompromised patients are most commonly affected^6-11; however, there also have been reports in healthy patients.^12,13 Infections typically present as painless erythematous papules or nodules that eventually suppurate, ulcerate, and become painful. Presentations involving Fitz-Hugh–Curtis syndrome,¹³ new B-cell lymphoma,¹⁰ and lymphadenitis¹² also have been described. Beyond cutaneous involvement, M haemophilum has been cultured from bone, the synovium, the lungs, and the central nervous system.^4,9 The majority of morbidities occur in patients with lung involvement.⁴ Therefore, even patients presenting with isolated cutaneous disease require close follow-up.

Mycobacterium haemophilum is a slowly proliferating organism that is unable to grow in standard egg-potato (Lowenstein-Jensen) medium or agar base (Middlebrook 7H10 or 7H11 agar) without iron supplementation (ferric ammonium citrate, hemin, or hemoglobin). It also requires temperatures of 30°C to 32°C for growth. Its iron requisite is unique, but species such as M marinum and Mycobacterium ulcerans also share reduced temperature requirements. Without a high index of suspicion, growth often is absent because standard Mycobacterium culture techniques will not foster organism growth. Our case demonstrated that special culture instructions must be relayed to the laboratory, even in the face of positive AFB smears. Failure to request hemin and modified incubation temperatures may have contributed to the negative AFB blood culture in our patient.

Due to the relatively rare incidence of M haemophilum infection, there are no known randomized controlled trials guiding antibiotic regimens. Infectious disease specialists often treat empirically with triple-drug therapy derived from locally reported species susceptibilities. The largest case series to date did not identify resistance to amikacin, ciprofloxacin, or clarithromycin.⁴ Our case identified a novel finding of ciprofloxacin and rifampin resistance, which may highlight the emergence of a newly resistant strain of M haemophilum. Of note, one case of rifampin resistance has been reported, but the culture was drawn from a postmortem specimen in the setting of previously rifampin-sensitive isolates.⁴ Empiric therapies should be guided by hospital susceptibility reports and expert consultation.

Coinfection with 2 or more NTM—including M tuberculosis, M leprae, and M fortuitum—has been reported.^8,14 Temporally distinct coinfections with M leprae and M haemophilum also have been described.¹⁵ Thus, practitioners should have a low threshold for repeat cultures in the context of new cutaneous nodules or granulomas, not only to detect concomitant infections but also to identify resistance patterns that might explain recurrent or recalcitrant disease. Immune reconstitution inflammatory syndrome also must be considered with new or worsening lesions, especially in the first months of therapy, as this is a common occurrence when immunosuppressive regimens are tapered to help manage infections.

In conclusion, M haemophilum is an underrecognized infection that presents as cutaneous nodules or lymphadenitis in immunocompromised or healthy individuals. Diagnosis requires a high index of suspicion because its unique growth requirements necessitate special laboratory techniques. Our case represents a classic presentation of this NTM infection in a patient with AML following allogenic stem cell transplantation. Repeat cultures, workup of potentially disseminated infections, and close follow-up are requisite to minimizing morbidity and mortality. A multidisciplinary approach involving infectious disease, medical oncology, radiology, and dermatology best manages this type of infection.

To the Editor:

The increase in nontuberculous mycobacteria (NTM) infections over the last 3 decades likely is multifaceted, including increased clinical awareness, improved laboratory diagnostics, growing numbers of immunocompromised patients, and an aging population.^1,2 Historically, the majority of mycobacteria-related diseases are due to Mycobacterium tuberculosis, Mycobacterium bovis, and Mycobacterium leprae.³

Mycobacterium haemophilum is a slow-growing acid-fast bacillus (AFB) that differs from other Mycobacterium species in that it requires iron-supplemented media and incubation temperatures of 30°C to 32°C for culture. As these requirements for growth are not standard for AFB cultures, M haemophilum infection may be underrecognized and underreported.³Mycobacterium haemophilum infections largely are cutaneous and generally are seen in AIDS patients and bone marrow transplant recipients who are iatrogenically immunosuppressed.^4,5 No species-specific treatment guidelines exist²; however, triple-drug therapy combining a macrolide, rifamycin, and a quinolone for a minimum of 12 months often is recommended.

A 64-year-old man with a history of coronary artery disease, hypertension, hyperlipidemia, and acute myelogenous leukemia (AML) underwent allogenic stem cell transplantation. His posttransplant course was complicated by multiple deep vein thromboses, hypogammaglobulinemia, and graft-vs-host disease (GVHD) of the skin and gastrointestinal tract that manifested as chronic diarrhea, which was managed with chronic prednisone. Thirteen months after the transplant, the patient presented to his outpatient oncologist (M.K.) for evaluation of painless, nonpruritic, erythematous papules and nodules that had emerged on the right side of the chest, right arm, and left leg of approximately 2 weeks’ duration.

On review of systems by oncology, the patient denied any fevers, chills, or night sweats but noted chronic loose nonbloody stools without abdominal pain, likely related to the GVHD. The patient’s medications included prednisone 20 mg once daily, fluconazole, amitriptyline, atovaquone, budesonide, dabigatran, metoprolol, pantoprazole, rosuvastatin, senna glycoside, spironolactone, tramadol, and valacyclovir.

Physical examination revealed multiple singular erythematous nodules on the right side of the chest (Figure 1A), right arm (Figure 1B), and left leg. There was no regional lymphadenopathy. The patient was afebrile and hemodynamically stable. A biopsy of the arm performed to rule out leukemia cutis revealed a granulomatous dermatitis with numerous AFB (Figures 2A and 2B), which were confirmed on Ziehl-Neelsen staining (Figures 2C and 2D). The presence of AFB raised concern for a disseminated mycobacterial infection. The patient was admitted to our institution approximately 1 week after the outpatient biopsy was performed. He was evaluated by infectious diseases (B.H.) and was recommended for repeat biopsy with AFB culture and for initiation of intravenous antibiotics.

The patient was evaluated by the dermatology consultation service on hospital day 1. At the time of consultation, the lesions were still painless but had enlarged. Two new satellite lesions were noted on his other extremities. Due to the widespread distribution of the lesions, there was concern for disseminated disease. The relatively rapid onset of new lesions increased concern for infection with rapid-growing mycobacteria, including Mycobacterium abscessus, Mycobacterium fortuitum, and Mycobacterium chelonae. A detailed history revealed that the patient’s wife had a fish tank, which supported the inclusion of Mycobacterium marinum in the differential; however, further questioning revealed that the patient never came in contact with the aquarium water. The initial outpatient biopsy had not been sent for culture. Following inpatient biopsy, the patient was initiated on empiric antimycobacterials, including imipenem, amikacin, clarithromycin, and levofloxacin. Computed tomography of the head was negative for cerebral involvement.

Acid-fast bacilli blood cultures were drawn per the recommendation from infectious diseases in an attempt to confirm disseminated disease; however, blood cultures remained negative. Tissue biopsy from the right arm was sent for AFB staining and culture. Many AFB were identified on microscopy, and growth was observed in the mycobacterial growth indicator tube after 6 days of incubation. The DNA probe was negative for M tuberculosis complex or Mycobacterium avium complex.

The patient was discharged on hospital day 6 on empiric therapy for rapid-growing mycobacteria while cultures were pending. The empiric regimen included intravenous imipenem 1 g every 6 hours, intravenous amikacin 1 g once daily, clarithromycin 500 mg every 12 hours, and levofloxacin 750 mg once daily. All solid media cultures were negative at the time of discharge.

The biopsy specimen proved difficult to culture on solid media using traditional methods. Three weeks after the inpatient biopsy, the microbiology laboratory reported that growth was observed on solid media that was incubated at 30°C and supplemented with iron. These findings were not characteristic of a rapidly growing mycobacteria (eg, M fortuitum, M chelonae, M abscessus) or M marinum but raised concern for infectionwith M haemophilum. Antimycobacterial treatment was adjusted to amikacin, clarithromycin, levofloxacin, and rifabutin.

Six weeks after the inpatient skin biopsy, final speciation confirmed infection with M haemophilum. The isolate proved susceptible to amikacin (minimal inhibitory concentration [MIC], 16), clarithromycin (MIC, 0.12), linezolid (MIC, <1), moxifloxacin (MIC, 0.5), rifabutin (MIC, <0.25), and trimethoprim-sulfamethoxazole (MIC, 0.5/9.5). The isolate was resistant to ciprofloxacin (MIC, 4), ethambutol (MIC, >16), and rifampin (MIC, 2). Based on these findings, an infectious disease specialist modified the treatment regimen to azithromycin 600 mg once daily, moxifloxacin 400 mg once daily, and rifabutin 300 mg once daily. Azithromycin was substituted for clarithromycin in an attempt to minimize the gastrointestinal side effects of the antibiotics. The infectious disease specialist was concerned that the clarithromycin could exacerbate the patient’s chronic GVHD-associated diarrhea, which posed a challenge to the oncologist, who was attempting to manage the patient’s GVHD and minimize the use of additional prednisone. At the time of this change, the patient was doing well clinically and denied any active skin lesions.

Four months later, he developed new left-sided neck swelling. Computed tomography revealed nonspecific enhancement involving the skin and superficial subcutaneous tissues in the left anterior neck. He was referred to otolaryngology given concern for recurrent infection vs leukemia cutis. He underwent excisional biopsy. Pathology was negative for malignancy but demonstrated subcutaneous necrotizing granulomatous inflammation with a positive AFB stain. Tissue AFB cultures revealed moderate AFB on direct stain, but there was no AFB growth at 12 weeks. Clarithromycin was restarted in place of azithromycin to increase the potency of the antimycobacterial regimen. Cultures from this neck biopsy were negative after 12 weeks of incubation.

In addition to this change in antibiotic coverage, the patient’s medical oncologist tapered the patient’s immunosuppression considerably. The patient subsequently completed 12 months of therapy with clarithromycin, moxifloxacin, and rifabutin starting from the time of the neck biopsy. He remained free of recurrence of mycobacterial infection for nearly 2 years until he died from an unrelated illness.

Nontuberculous mycobacteria are an ubiquitous environmental group.² Sources include soil and natural water (M avium), fish tanks and swimming pools (M marinum), and tap water and occasionally domestic animals (Mycobacterium kansasii). Additionally, rapidly growing NTM such as M abscessus, M chelonae, and M fortuitum have been isolated from soil and natural water supplies.³

Mycobacterium haemophilum is a fastidious organism with a predilection for skin of the chest and extremities. Iatrogenically or inherently immunocompromised patients are most commonly affected^6-11; however, there also have been reports in healthy patients.^12,13 Infections typically present as painless erythematous papules or nodules that eventually suppurate, ulcerate, and become painful. Presentations involving Fitz-Hugh–Curtis syndrome,¹³ new B-cell lymphoma,¹⁰ and lymphadenitis¹² also have been described. Beyond cutaneous involvement, M haemophilum has been cultured from bone, the synovium, the lungs, and the central nervous system.^4,9 The majority of morbidities occur in patients with lung involvement.⁴ Therefore, even patients presenting with isolated cutaneous disease require close follow-up.

Mycobacterium haemophilum is a slowly proliferating organism that is unable to grow in standard egg-potato (Lowenstein-Jensen) medium or agar base (Middlebrook 7H10 or 7H11 agar) without iron supplementation (ferric ammonium citrate, hemin, or hemoglobin). It also requires temperatures of 30°C to 32°C for growth. Its iron requisite is unique, but species such as M marinum and Mycobacterium ulcerans also share reduced temperature requirements. Without a high index of suspicion, growth often is absent because standard Mycobacterium culture techniques will not foster organism growth. Our case demonstrated that special culture instructions must be relayed to the laboratory, even in the face of positive AFB smears. Failure to request hemin and modified incubation temperatures may have contributed to the negative AFB blood culture in our patient.

Due to the relatively rare incidence of M haemophilum infection, there are no known randomized controlled trials guiding antibiotic regimens. Infectious disease specialists often treat empirically with triple-drug therapy derived from locally reported species susceptibilities. The largest case series to date did not identify resistance to amikacin, ciprofloxacin, or clarithromycin.⁴ Our case identified a novel finding of ciprofloxacin and rifampin resistance, which may highlight the emergence of a newly resistant strain of M haemophilum. Of note, one case of rifampin resistance has been reported, but the culture was drawn from a postmortem specimen in the setting of previously rifampin-sensitive isolates.⁴ Empiric therapies should be guided by hospital susceptibility reports and expert consultation.

Coinfection with 2 or more NTM—including M tuberculosis, M leprae, and M fortuitum—has been reported.^8,14 Temporally distinct coinfections with M leprae and M haemophilum also have been described.¹⁵ Thus, practitioners should have a low threshold for repeat cultures in the context of new cutaneous nodules or granulomas, not only to detect concomitant infections but also to identify resistance patterns that might explain recurrent or recalcitrant disease. Immune reconstitution inflammatory syndrome also must be considered with new or worsening lesions, especially in the first months of therapy, as this is a common occurrence when immunosuppressive regimens are tapered to help manage infections.

In conclusion, M haemophilum is an underrecognized infection that presents as cutaneous nodules or lymphadenitis in immunocompromised or healthy individuals. Diagnosis requires a high index of suspicion because its unique growth requirements necessitate special laboratory techniques. Our case represents a classic presentation of this NTM infection in a patient with AML following allogenic stem cell transplantation. Repeat cultures, workup of potentially disseminated infections, and close follow-up are requisite to minimizing morbidity and mortality. A multidisciplinary approach involving infectious disease, medical oncology, radiology, and dermatology best manages this type of infection.

To the Editor:

The increase in nontuberculous mycobacteria (NTM) infections over the last 3 decades likely is multifaceted, including increased clinical awareness, improved laboratory diagnostics, growing numbers of immunocompromised patients, and an aging population.^1,2 Historically, the majority of mycobacteria-related diseases are due to Mycobacterium tuberculosis, Mycobacterium bovis, and Mycobacterium leprae.³

Mycobacterium haemophilum is a slow-growing acid-fast bacillus (AFB) that differs from other Mycobacterium species in that it requires iron-supplemented media and incubation temperatures of 30°C to 32°C for culture. As these requirements for growth are not standard for AFB cultures, M haemophilum infection may be underrecognized and underreported.³Mycobacterium haemophilum infections largely are cutaneous and generally are seen in AIDS patients and bone marrow transplant recipients who are iatrogenically immunosuppressed.^4,5 No species-specific treatment guidelines exist²; however, triple-drug therapy combining a macrolide, rifamycin, and a quinolone for a minimum of 12 months often is recommended.

A 64-year-old man with a history of coronary artery disease, hypertension, hyperlipidemia, and acute myelogenous leukemia (AML) underwent allogenic stem cell transplantation. His posttransplant course was complicated by multiple deep vein thromboses, hypogammaglobulinemia, and graft-vs-host disease (GVHD) of the skin and gastrointestinal tract that manifested as chronic diarrhea, which was managed with chronic prednisone. Thirteen months after the transplant, the patient presented to his outpatient oncologist (M.K.) for evaluation of painless, nonpruritic, erythematous papules and nodules that had emerged on the right side of the chest, right arm, and left leg of approximately 2 weeks’ duration.

On review of systems by oncology, the patient denied any fevers, chills, or night sweats but noted chronic loose nonbloody stools without abdominal pain, likely related to the GVHD. The patient’s medications included prednisone 20 mg once daily, fluconazole, amitriptyline, atovaquone, budesonide, dabigatran, metoprolol, pantoprazole, rosuvastatin, senna glycoside, spironolactone, tramadol, and valacyclovir.

Physical examination revealed multiple singular erythematous nodules on the right side of the chest (Figure 1A), right arm (Figure 1B), and left leg. There was no regional lymphadenopathy. The patient was afebrile and hemodynamically stable. A biopsy of the arm performed to rule out leukemia cutis revealed a granulomatous dermatitis with numerous AFB (Figures 2A and 2B), which were confirmed on Ziehl-Neelsen staining (Figures 2C and 2D). The presence of AFB raised concern for a disseminated mycobacterial infection. The patient was admitted to our institution approximately 1 week after the outpatient biopsy was performed. He was evaluated by infectious diseases (B.H.) and was recommended for repeat biopsy with AFB culture and for initiation of intravenous antibiotics.

The patient was evaluated by the dermatology consultation service on hospital day 1. At the time of consultation, the lesions were still painless but had enlarged. Two new satellite lesions were noted on his other extremities. Due to the widespread distribution of the lesions, there was concern for disseminated disease. The relatively rapid onset of new lesions increased concern for infection with rapid-growing mycobacteria, including Mycobacterium abscessus, Mycobacterium fortuitum, and Mycobacterium chelonae. A detailed history revealed that the patient’s wife had a fish tank, which supported the inclusion of Mycobacterium marinum in the differential; however, further questioning revealed that the patient never came in contact with the aquarium water. The initial outpatient biopsy had not been sent for culture. Following inpatient biopsy, the patient was initiated on empiric antimycobacterials, including imipenem, amikacin, clarithromycin, and levofloxacin. Computed tomography of the head was negative for cerebral involvement.

Acid-fast bacilli blood cultures were drawn per the recommendation from infectious diseases in an attempt to confirm disseminated disease; however, blood cultures remained negative. Tissue biopsy from the right arm was sent for AFB staining and culture. Many AFB were identified on microscopy, and growth was observed in the mycobacterial growth indicator tube after 6 days of incubation. The DNA probe was negative for M tuberculosis complex or Mycobacterium avium complex.

The patient was discharged on hospital day 6 on empiric therapy for rapid-growing mycobacteria while cultures were pending. The empiric regimen included intravenous imipenem 1 g every 6 hours, intravenous amikacin 1 g once daily, clarithromycin 500 mg every 12 hours, and levofloxacin 750 mg once daily. All solid media cultures were negative at the time of discharge.

The biopsy specimen proved difficult to culture on solid media using traditional methods. Three weeks after the inpatient biopsy, the microbiology laboratory reported that growth was observed on solid media that was incubated at 30°C and supplemented with iron. These findings were not characteristic of a rapidly growing mycobacteria (eg, M fortuitum, M chelonae, M abscessus) or M marinum but raised concern for infectionwith M haemophilum. Antimycobacterial treatment was adjusted to amikacin, clarithromycin, levofloxacin, and rifabutin.

Six weeks after the inpatient skin biopsy, final speciation confirmed infection with M haemophilum. The isolate proved susceptible to amikacin (minimal inhibitory concentration [MIC], 16), clarithromycin (MIC, 0.12), linezolid (MIC, <1), moxifloxacin (MIC, 0.5), rifabutin (MIC, <0.25), and trimethoprim-sulfamethoxazole (MIC, 0.5/9.5). The isolate was resistant to ciprofloxacin (MIC, 4), ethambutol (MIC, >16), and rifampin (MIC, 2). Based on these findings, an infectious disease specialist modified the treatment regimen to azithromycin 600 mg once daily, moxifloxacin 400 mg once daily, and rifabutin 300 mg once daily. Azithromycin was substituted for clarithromycin in an attempt to minimize the gastrointestinal side effects of the antibiotics. The infectious disease specialist was concerned that the clarithromycin could exacerbate the patient’s chronic GVHD-associated diarrhea, which posed a challenge to the oncologist, who was attempting to manage the patient’s GVHD and minimize the use of additional prednisone. At the time of this change, the patient was doing well clinically and denied any active skin lesions.

Four months later, he developed new left-sided neck swelling. Computed tomography revealed nonspecific enhancement involving the skin and superficial subcutaneous tissues in the left anterior neck. He was referred to otolaryngology given concern for recurrent infection vs leukemia cutis. He underwent excisional biopsy. Pathology was negative for malignancy but demonstrated subcutaneous necrotizing granulomatous inflammation with a positive AFB stain. Tissue AFB cultures revealed moderate AFB on direct stain, but there was no AFB growth at 12 weeks. Clarithromycin was restarted in place of azithromycin to increase the potency of the antimycobacterial regimen. Cultures from this neck biopsy were negative after 12 weeks of incubation.

In addition to this change in antibiotic coverage, the patient’s medical oncologist tapered the patient’s immunosuppression considerably. The patient subsequently completed 12 months of therapy with clarithromycin, moxifloxacin, and rifabutin starting from the time of the neck biopsy. He remained free of recurrence of mycobacterial infection for nearly 2 years until he died from an unrelated illness.

Nontuberculous mycobacteria are an ubiquitous environmental group.² Sources include soil and natural water (M avium), fish tanks and swimming pools (M marinum), and tap water and occasionally domestic animals (Mycobacterium kansasii). Additionally, rapidly growing NTM such as M abscessus, M chelonae, and M fortuitum have been isolated from soil and natural water supplies.³

Mycobacterium haemophilum is a fastidious organism with a predilection for skin of the chest and extremities. Iatrogenically or inherently immunocompromised patients are most commonly affected^6-11; however, there also have been reports in healthy patients.^12,13 Infections typically present as painless erythematous papules or nodules that eventually suppurate, ulcerate, and become painful. Presentations involving Fitz-Hugh–Curtis syndrome,¹³ new B-cell lymphoma,¹⁰ and lymphadenitis¹² also have been described. Beyond cutaneous involvement, M haemophilum has been cultured from bone, the synovium, the lungs, and the central nervous system.^4,9 The majority of morbidities occur in patients with lung involvement.⁴ Therefore, even patients presenting with isolated cutaneous disease require close follow-up.

Mycobacterium haemophilum is a slowly proliferating organism that is unable to grow in standard egg-potato (Lowenstein-Jensen) medium or agar base (Middlebrook 7H10 or 7H11 agar) without iron supplementation (ferric ammonium citrate, hemin, or hemoglobin). It also requires temperatures of 30°C to 32°C for growth. Its iron requisite is unique, but species such as M marinum and Mycobacterium ulcerans also share reduced temperature requirements. Without a high index of suspicion, growth often is absent because standard Mycobacterium culture techniques will not foster organism growth. Our case demonstrated that special culture instructions must be relayed to the laboratory, even in the face of positive AFB smears. Failure to request hemin and modified incubation temperatures may have contributed to the negative AFB blood culture in our patient.

Due to the relatively rare incidence of M haemophilum infection, there are no known randomized controlled trials guiding antibiotic regimens. Infectious disease specialists often treat empirically with triple-drug therapy derived from locally reported species susceptibilities. The largest case series to date did not identify resistance to amikacin, ciprofloxacin, or clarithromycin.⁴ Our case identified a novel finding of ciprofloxacin and rifampin resistance, which may highlight the emergence of a newly resistant strain of M haemophilum. Of note, one case of rifampin resistance has been reported, but the culture was drawn from a postmortem specimen in the setting of previously rifampin-sensitive isolates.⁴ Empiric therapies should be guided by hospital susceptibility reports and expert consultation.

Coinfection with 2 or more NTM—including M tuberculosis, M leprae, and M fortuitum—has been reported.^8,14 Temporally distinct coinfections with M leprae and M haemophilum also have been described.¹⁵ Thus, practitioners should have a low threshold for repeat cultures in the context of new cutaneous nodules or granulomas, not only to detect concomitant infections but also to identify resistance patterns that might explain recurrent or recalcitrant disease. Immune reconstitution inflammatory syndrome also must be considered with new or worsening lesions, especially in the first months of therapy, as this is a common occurrence when immunosuppressive regimens are tapered to help manage infections.

In conclusion, M haemophilum is an underrecognized infection that presents as cutaneous nodules or lymphadenitis in immunocompromised or healthy individuals. Diagnosis requires a high index of suspicion because its unique growth requirements necessitate special laboratory techniques. Our case represents a classic presentation of this NTM infection in a patient with AML following allogenic stem cell transplantation. Repeat cultures, workup of potentially disseminated infections, and close follow-up are requisite to minimizing morbidity and mortality. A multidisciplinary approach involving infectious disease, medical oncology, radiology, and dermatology best manages this type of infection.

ALVAC-HIV vaccine showed immunogenicity across several HIV clades in an early trial involving 100 healthy patients at low risk of HIV infection, according to a study by Glenda E. Gray, MBBCH, FCPaed, of the University of the Witwatersrand, Johannesburg, South Africa, and colleagues that was published online in the Sep. 18 issue of Science Translational Medicine.

ALVAC-HIV (vCP1521) is a live attenuated recombinant canarypox-derived virus that expresses gene products from the HIV-1 gp120 (92TH023/clade E), Gag (clade B), and Pro (clade B) that is cultured in chicken embryo fibroblast cells.

Four injections of ALVAC-HIV were given at months 0, 1, 3, and 6. At months 3 and 6, two booster injections were given of AIDSVAX/BE, a bivalent HIV glycoprotein 120 (gp120) that was previously studied in the RV144 trial. The HVTN 097 trial examined primary immunogenicity endpoints including the frequency and magnitude of IgG and IgG3 antibody binding, measured in serum specimens obtained at baseline, at a peak time point (2 weeks after second ALVAC/AIDSVAX vaccination), a durability time point (6 months after second ALVAC/AIDSVAX vaccination), and the response rates and magnitudes of CD4+ and CD8+ T-cell responses at the baseline, peak, and durability time points. One hundred healthy adults at low risk for HIV infection were randomized in 3:1:1 ratio to group T1 (HIV vaccines, tetanus vaccine, and hepatitis B vaccine), group T2 (HIV vaccine only), and the placebo group T3 (tetanus vaccine and hepatitis B vaccine). There were no meaningful differences in HIV immune responses between the HIV vaccine recipients with or without the tetanus and hepatitis B vaccines, so the researchers pooled the data from groups T1 and T2 in their analysis.

At the peak immunogenicity time point, the vaccine schedule predominantly induced CD4+ T cells directed to HIV-1 Env; this was measured by expression of interleukin-2 and/or interferon-gamma. The Env-specific CD4+ T-cell response rate was significantly higher in HVTN 097 vaccine recipients than it was in those in the RV144 trial (51.9% vs. 36.4%; P = .043). The HVTN 097 trial also showed significantly higher response rates for CD40L(59.3% for HVTN 097 vs. 33.7% for RV144; P less than .001) and for interferon-gamma (42.6% in HVTN 097 vs. 19.5% in RV144; P = .001).

However, durability at 6 months after the second vaccine injection remained an issue, with the frequency of circulating Env-specific CD4+ T-cell responses among vaccine recipients declining significantly; the response rate dropped from 70.8% to 36.1%.

“These data may indicate that cross-clade immune responses, especially to non-neutralizing epitopes correlated with decreased HIV-1 risk, can be achieved for a globally effective vaccine by using unique HIV Env strains,” Dr. Gray and associates concluded.

The authors declared that they had no competing interests.

[email protected]

SOURCE: Gray GE et al. Sci. Transl. Med. 2019 Sep 18. doi: 10.1126/scitranslmed.aax1880..

ALVAC-HIV vaccine showed immunogenicity across several HIV clades in an early trial involving 100 healthy patients at low risk of HIV infection, according to a study by Glenda E. Gray, MBBCH, FCPaed, of the University of the Witwatersrand, Johannesburg, South Africa, and colleagues that was published online in the Sep. 18 issue of Science Translational Medicine.

ALVAC-HIV (vCP1521) is a live attenuated recombinant canarypox-derived virus that expresses gene products from the HIV-1 gp120 (92TH023/clade E), Gag (clade B), and Pro (clade B) that is cultured in chicken embryo fibroblast cells.

Four injections of ALVAC-HIV were given at months 0, 1, 3, and 6. At months 3 and 6, two booster injections were given of AIDSVAX/BE, a bivalent HIV glycoprotein 120 (gp120) that was previously studied in the RV144 trial. The HVTN 097 trial examined primary immunogenicity endpoints including the frequency and magnitude of IgG and IgG3 antibody binding, measured in serum specimens obtained at baseline, at a peak time point (2 weeks after second ALVAC/AIDSVAX vaccination), a durability time point (6 months after second ALVAC/AIDSVAX vaccination), and the response rates and magnitudes of CD4+ and CD8+ T-cell responses at the baseline, peak, and durability time points. One hundred healthy adults at low risk for HIV infection were randomized in 3:1:1 ratio to group T1 (HIV vaccines, tetanus vaccine, and hepatitis B vaccine), group T2 (HIV vaccine only), and the placebo group T3 (tetanus vaccine and hepatitis B vaccine). There were no meaningful differences in HIV immune responses between the HIV vaccine recipients with or without the tetanus and hepatitis B vaccines, so the researchers pooled the data from groups T1 and T2 in their analysis.

At the peak immunogenicity time point, the vaccine schedule predominantly induced CD4+ T cells directed to HIV-1 Env; this was measured by expression of interleukin-2 and/or interferon-gamma. The Env-specific CD4+ T-cell response rate was significantly higher in HVTN 097 vaccine recipients than it was in those in the RV144 trial (51.9% vs. 36.4%; P = .043). The HVTN 097 trial also showed significantly higher response rates for CD40L(59.3% for HVTN 097 vs. 33.7% for RV144; P less than .001) and for interferon-gamma (42.6% in HVTN 097 vs. 19.5% in RV144; P = .001).

However, durability at 6 months after the second vaccine injection remained an issue, with the frequency of circulating Env-specific CD4+ T-cell responses among vaccine recipients declining significantly; the response rate dropped from 70.8% to 36.1%.

“These data may indicate that cross-clade immune responses, especially to non-neutralizing epitopes correlated with decreased HIV-1 risk, can be achieved for a globally effective vaccine by using unique HIV Env strains,” Dr. Gray and associates concluded.

The authors declared that they had no competing interests.

[email protected]

SOURCE: Gray GE et al. Sci. Transl. Med. 2019 Sep 18. doi: 10.1126/scitranslmed.aax1880..

ALVAC-HIV vaccine showed immunogenicity across several HIV clades in an early trial involving 100 healthy patients at low risk of HIV infection, according to a study by Glenda E. Gray, MBBCH, FCPaed, of the University of the Witwatersrand, Johannesburg, South Africa, and colleagues that was published online in the Sep. 18 issue of Science Translational Medicine.

ALVAC-HIV (vCP1521) is a live attenuated recombinant canarypox-derived virus that expresses gene products from the HIV-1 gp120 (92TH023/clade E), Gag (clade B), and Pro (clade B) that is cultured in chicken embryo fibroblast cells.

Four injections of ALVAC-HIV were given at months 0, 1, 3, and 6. At months 3 and 6, two booster injections were given of AIDSVAX/BE, a bivalent HIV glycoprotein 120 (gp120) that was previously studied in the RV144 trial. The HVTN 097 trial examined primary immunogenicity endpoints including the frequency and magnitude of IgG and IgG3 antibody binding, measured in serum specimens obtained at baseline, at a peak time point (2 weeks after second ALVAC/AIDSVAX vaccination), a durability time point (6 months after second ALVAC/AIDSVAX vaccination), and the response rates and magnitudes of CD4+ and CD8+ T-cell responses at the baseline, peak, and durability time points. One hundred healthy adults at low risk for HIV infection were randomized in 3:1:1 ratio to group T1 (HIV vaccines, tetanus vaccine, and hepatitis B vaccine), group T2 (HIV vaccine only), and the placebo group T3 (tetanus vaccine and hepatitis B vaccine). There were no meaningful differences in HIV immune responses between the HIV vaccine recipients with or without the tetanus and hepatitis B vaccines, so the researchers pooled the data from groups T1 and T2 in their analysis.

At the peak immunogenicity time point, the vaccine schedule predominantly induced CD4+ T cells directed to HIV-1 Env; this was measured by expression of interleukin-2 and/or interferon-gamma. The Env-specific CD4+ T-cell response rate was significantly higher in HVTN 097 vaccine recipients than it was in those in the RV144 trial (51.9% vs. 36.4%; P = .043). The HVTN 097 trial also showed significantly higher response rates for CD40L(59.3% for HVTN 097 vs. 33.7% for RV144; P less than .001) and for interferon-gamma (42.6% in HVTN 097 vs. 19.5% in RV144; P = .001).

However, durability at 6 months after the second vaccine injection remained an issue, with the frequency of circulating Env-specific CD4+ T-cell responses among vaccine recipients declining significantly; the response rate dropped from 70.8% to 36.1%.

“These data may indicate that cross-clade immune responses, especially to non-neutralizing epitopes correlated with decreased HIV-1 risk, can be achieved for a globally effective vaccine by using unique HIV Env strains,” Dr. Gray and associates concluded.

The authors declared that they had no competing interests.

[email protected]

SOURCE: Gray GE et al. Sci. Transl. Med. 2019 Sep 18. doi: 10.1126/scitranslmed.aax1880..

In 2017, the Australian state of New South Wales experienced an outbreak of rotavirus gastroenteritis in children despite a high level of rotavirus immunization. In a new study, researchers reported evidence that suggests a decline in vaccine effectiveness (VE) isn’t the cause, although they found that VE declines over time as children age.

CDC/Dr. Erskine Palmer

“More analysis is required to investigate how novel or unusual strains ... interact with rotavirus vaccines and whether antigenic changes affect VE and challenge vaccination programs,” the study authors wrote in Pediatrics.

Researchers led by Julia E. Maguire, BSc, MSci(Epi), of Australia’s National Center for Immunization Research and the Australian National University, Canberra, launched the analysis in the wake of a 2017 outbreak of 2,319 rotavirus cases in New South Wales, a 210% increase over the rate in 2016. (The state, the largest in Australia, has about 7.5 million residents.)

The study authors tracked VE from 2010 to 2017 by analyzing 9,517 rotavirus cases in the state (50% male; median age, 5 years). Half weren’t eligible for rotavirus immunization because of their age; of the rest, 31% weren’t vaccinated.

Ms. Maguire and associates found that VE did not decline in 2017 and doesn’t seem to be responsible for the Australian rotavirus outbreak. “In our study, two doses of RV1 [the Rotarix vaccine] was 73.7% effective in protecting children aged 6 months to 9 years against laboratory-confirmed rotavirus over our 8-year study period. Somewhat surprisingly in the 2017 outbreak year, a high two-dose VE of 88.4% in those aged 6-11 months was also observed.”

They added that “the median age of rotavirus cases has increased in Australia over the last 8 years from 3.9 years in 2010 to 7.1 years in 2017. Adults and older children born before the availability of vaccination in Australia are unimmunized and may have been less likely to have repeated subclinical infections because of reductions in virus circulation overall, resulting in less immune boosting.”

Going forward, the study authors wrote that “investigation of population-level VE in relation to rotavirus genotype data should continue in a range of settings to improve our understanding of rotavirus vaccines and the impact they have on disease across the age spectrum over time.”

In an accompanying commentary, Benjamin Lee, MD, and E. Ross Colgate, PhD, of the University of Vermont, Burlington, wrote that Australia’s adoption of rotavirus immunization in 2017 “with state-level implementation of either Rotarix or RotaTeq ... enabled a fascinating natural experiment of VE and strain selection.”

Pressure from vaccines “potentially enables the emergence of novel strains,” they wrote. “Despite this, large-scale strain replacement has not been demonstrated in rotaviruses, in contrast to the development of pneumococcal serotype replacement that was seen after pneumococcal conjugate vaccine introduction. Similarly, there has been no evidence of widespread vaccine escape due to antigenic drift or shift, as occurs with another important segmented RNA virus, influenza A.”

As Dr. Lee and Dr. Colgate noted, 100 million children worldwide remain unvaccinated against rotavirus, and more than 128,000 die because of rotavirus-associated gastroenteritis each year. “Improving vaccine access and coverage and solving the riddle of [oral rotavirus vaccine] underperformance in low-income countries are urgent priorities, which may ultimately require next-generation oral and/or parenteral vaccines, a number of which are under development and in clinical trials. In addition, because the emergence of novel strains of disease-causing pathogens is always a possibility, vigilance in rotavirus surveillance, including genotype assessment, should remain a priority for public health programs.”

The study was funded by Australia’s National Center for Immunization Research and Surveillance, which receives government funding. The Australian Rotavirus Surveillance Program is supported by government funding and the vaccine companies Commonwealth Serum Laboratories and GlaxoSmithKline. Ms. Maguire is supported by an Australian Government Research Training Program Scholarship. One author is director of the Australian Rotavirus Surveillance Program, which received funding as above. The other study authors and the commentary authors reported no relevant financial disclosures.

SOURCES: Maguire JE et al. Pediatrics. 2019 Sep 17. doi: 10.1542/peds.2019-1024; Lee B, Colgate ER. Pediatrics. 2019 Sep 17. doi: 10.1542/peds.2019-2426.

In 2017, the Australian state of New South Wales experienced an outbreak of rotavirus gastroenteritis in children despite a high level of rotavirus immunization. In a new study, researchers reported evidence that suggests a decline in vaccine effectiveness (VE) isn’t the cause, although they found that VE declines over time as children age.

CDC/Dr. Erskine Palmer

“More analysis is required to investigate how novel or unusual strains ... interact with rotavirus vaccines and whether antigenic changes affect VE and challenge vaccination programs,” the study authors wrote in Pediatrics.

Researchers led by Julia E. Maguire, BSc, MSci(Epi), of Australia’s National Center for Immunization Research and the Australian National University, Canberra, launched the analysis in the wake of a 2017 outbreak of 2,319 rotavirus cases in New South Wales, a 210% increase over the rate in 2016. (The state, the largest in Australia, has about 7.5 million residents.)

The study authors tracked VE from 2010 to 2017 by analyzing 9,517 rotavirus cases in the state (50% male; median age, 5 years). Half weren’t eligible for rotavirus immunization because of their age; of the rest, 31% weren’t vaccinated.

Ms. Maguire and associates found that VE did not decline in 2017 and doesn’t seem to be responsible for the Australian rotavirus outbreak. “In our study, two doses of RV1 [the Rotarix vaccine] was 73.7% effective in protecting children aged 6 months to 9 years against laboratory-confirmed rotavirus over our 8-year study period. Somewhat surprisingly in the 2017 outbreak year, a high two-dose VE of 88.4% in those aged 6-11 months was also observed.”

They added that “the median age of rotavirus cases has increased in Australia over the last 8 years from 3.9 years in 2010 to 7.1 years in 2017. Adults and older children born before the availability of vaccination in Australia are unimmunized and may have been less likely to have repeated subclinical infections because of reductions in virus circulation overall, resulting in less immune boosting.”

Going forward, the study authors wrote that “investigation of population-level VE in relation to rotavirus genotype data should continue in a range of settings to improve our understanding of rotavirus vaccines and the impact they have on disease across the age spectrum over time.”

In an accompanying commentary, Benjamin Lee, MD, and E. Ross Colgate, PhD, of the University of Vermont, Burlington, wrote that Australia’s adoption of rotavirus immunization in 2017 “with state-level implementation of either Rotarix or RotaTeq ... enabled a fascinating natural experiment of VE and strain selection.”

Pressure from vaccines “potentially enables the emergence of novel strains,” they wrote. “Despite this, large-scale strain replacement has not been demonstrated in rotaviruses, in contrast to the development of pneumococcal serotype replacement that was seen after pneumococcal conjugate vaccine introduction. Similarly, there has been no evidence of widespread vaccine escape due to antigenic drift or shift, as occurs with another important segmented RNA virus, influenza A.”

As Dr. Lee and Dr. Colgate noted, 100 million children worldwide remain unvaccinated against rotavirus, and more than 128,000 die because of rotavirus-associated gastroenteritis each year. “Improving vaccine access and coverage and solving the riddle of [oral rotavirus vaccine] underperformance in low-income countries are urgent priorities, which may ultimately require next-generation oral and/or parenteral vaccines, a number of which are under development and in clinical trials. In addition, because the emergence of novel strains of disease-causing pathogens is always a possibility, vigilance in rotavirus surveillance, including genotype assessment, should remain a priority for public health programs.”

The study was funded by Australia’s National Center for Immunization Research and Surveillance, which receives government funding. The Australian Rotavirus Surveillance Program is supported by government funding and the vaccine companies Commonwealth Serum Laboratories and GlaxoSmithKline. Ms. Maguire is supported by an Australian Government Research Training Program Scholarship. One author is director of the Australian Rotavirus Surveillance Program, which received funding as above. The other study authors and the commentary authors reported no relevant financial disclosures.

SOURCES: Maguire JE et al. Pediatrics. 2019 Sep 17. doi: 10.1542/peds.2019-1024; Lee B, Colgate ER. Pediatrics. 2019 Sep 17. doi: 10.1542/peds.2019-2426.

In 2017, the Australian state of New South Wales experienced an outbreak of rotavirus gastroenteritis in children despite a high level of rotavirus immunization. In a new study, researchers reported evidence that suggests a decline in vaccine effectiveness (VE) isn’t the cause, although they found that VE declines over time as children age.

CDC/Dr. Erskine Palmer

“More analysis is required to investigate how novel or unusual strains ... interact with rotavirus vaccines and whether antigenic changes affect VE and challenge vaccination programs,” the study authors wrote in Pediatrics.

Researchers led by Julia E. Maguire, BSc, MSci(Epi), of Australia’s National Center for Immunization Research and the Australian National University, Canberra, launched the analysis in the wake of a 2017 outbreak of 2,319 rotavirus cases in New South Wales, a 210% increase over the rate in 2016. (The state, the largest in Australia, has about 7.5 million residents.)

The study authors tracked VE from 2010 to 2017 by analyzing 9,517 rotavirus cases in the state (50% male; median age, 5 years). Half weren’t eligible for rotavirus immunization because of their age; of the rest, 31% weren’t vaccinated.

Ms. Maguire and associates found that VE did not decline in 2017 and doesn’t seem to be responsible for the Australian rotavirus outbreak. “In our study, two doses of RV1 [the Rotarix vaccine] was 73.7% effective in protecting children aged 6 months to 9 years against laboratory-confirmed rotavirus over our 8-year study period. Somewhat surprisingly in the 2017 outbreak year, a high two-dose VE of 88.4% in those aged 6-11 months was also observed.”

They added that “the median age of rotavirus cases has increased in Australia over the last 8 years from 3.9 years in 2010 to 7.1 years in 2017. Adults and older children born before the availability of vaccination in Australia are unimmunized and may have been less likely to have repeated subclinical infections because of reductions in virus circulation overall, resulting in less immune boosting.”

Going forward, the study authors wrote that “investigation of population-level VE in relation to rotavirus genotype data should continue in a range of settings to improve our understanding of rotavirus vaccines and the impact they have on disease across the age spectrum over time.”

In an accompanying commentary, Benjamin Lee, MD, and E. Ross Colgate, PhD, of the University of Vermont, Burlington, wrote that Australia’s adoption of rotavirus immunization in 2017 “with state-level implementation of either Rotarix or RotaTeq ... enabled a fascinating natural experiment of VE and strain selection.”

Pressure from vaccines “potentially enables the emergence of novel strains,” they wrote. “Despite this, large-scale strain replacement has not been demonstrated in rotaviruses, in contrast to the development of pneumococcal serotype replacement that was seen after pneumococcal conjugate vaccine introduction. Similarly, there has been no evidence of widespread vaccine escape due to antigenic drift or shift, as occurs with another important segmented RNA virus, influenza A.”

As Dr. Lee and Dr. Colgate noted, 100 million children worldwide remain unvaccinated against rotavirus, and more than 128,000 die because of rotavirus-associated gastroenteritis each year. “Improving vaccine access and coverage and solving the riddle of [oral rotavirus vaccine] underperformance in low-income countries are urgent priorities, which may ultimately require next-generation oral and/or parenteral vaccines, a number of which are under development and in clinical trials. In addition, because the emergence of novel strains of disease-causing pathogens is always a possibility, vigilance in rotavirus surveillance, including genotype assessment, should remain a priority for public health programs.”

The study was funded by Australia’s National Center for Immunization Research and Surveillance, which receives government funding. The Australian Rotavirus Surveillance Program is supported by government funding and the vaccine companies Commonwealth Serum Laboratories and GlaxoSmithKline. Ms. Maguire is supported by an Australian Government Research Training Program Scholarship. One author is director of the Australian Rotavirus Surveillance Program, which received funding as above. The other study authors and the commentary authors reported no relevant financial disclosures.

SOURCES: Maguire JE et al. Pediatrics. 2019 Sep 17. doi: 10.1542/peds.2019-1024; Lee B, Colgate ER. Pediatrics. 2019 Sep 17. doi: 10.1542/peds.2019-2426.

Mycoplasma pneumoniae infection commonly manifests as an upper or lower respiratory tract infection with associated fever, dyspnea, cough, and coryza. However, patients can present with extrapulmonary complications with dermatologic findings including mucocutaneous eruptions. M. pneumoniae–associated mucocutaneous disease has prominent mucositis and typically sparse cutaneous involvement. The mucositis usually involves the lips and oral mucosa, eye conjunctivae, and nasal mucosa and can involve urogenital lesions. It predominantly is observed in children and adolescents. This condition is essentially a subtype of Stevens-Johnson syndrome, with a specific infection-associated etiology, and has been called “Mycoplasma pneumoniae–induced rash and mucositis,” shortened to “MIRM.”

Severe reactive mucocutaneous eruptions include erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). While there has been semantic confusion over the years, there are some distinctive characteristics.

EM is characterized by typical three-ringed target papules that are predominantly acral in location and often without mucosal involvement. The lesions are “multiforme” in that they can appear polymorphous and evolve during an episode, with erythematous macules progressing to edematous papules, sometimes with a halo of pallor and concentric “target-like” appearance. Lesions of EM are fixed, meaning individual lesions last 7-10 days, unlike urticarial lesions that last hours. EM classically is associated with herpes simplex virus infections which usually precede its development.

SJS and TEN display atypical macules and papules which develop into erythematous vesicles, bullae, and potentially extensive desquamation, usually presenting with fever and systemic symptoms, with multiple mucosal sites involved. SJS usually is defined by having bullae restricted to less than 10% of body surface area (BSA), TEN as greater than 30% BSA, and “overlap SJS-TEN” as 20%-30% skin detachment.¹ SJS and TEN commonly are induced by medications and on a spectrum of drug hypersensitivity–induced epidermal necrolysis.

MIRM has been highlighted as a distinct, common condition, usually mucous-membrane predominant with involvement of two or more mucosal sites, less than 10% total BSA, the presence of few vesiculobullous lesions or scattered atypical targets with or without targetoid lesions (without rash is called MIRM sine rash), and clinical and laboratory evidence of atypical pneumonia.² Other infections can cause similar eruptions (for example, Chlamydia pneumoniae), and a recent proposal by the Pediatric Dermatology Research Alliance has suggested the term “Reactive Infectious Mucocutaneous Eruption” (RIME) to include MIRM and other infection-induced reactions.

Laboratory diagnosis of M. pneumoniae is via serology or polymerase chain reaction. Antibody titers begin to rise approximately 7-9 days after infection and peak at 3-4 weeks. Enzyme immunoassay is more sensitive in detecting acute infection than culture and has sensitivity comparable to the polymerase chain reaction if there has been sufficient time to develop an antibody response.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. Dr. Bhatti is a research fellow in pediatric dermatology at Rady Children’s Hospital and the University of California, San Diego. They said they have no financial disclosures. Email Dr. Eichenfield and Dr. Bhatti at [email protected].

References

1. Arch Dermatol. 1993 Jan;129(1):92-6.

2. J Am Acad Dermatol. 2015 Feb;72(2):239-45.

Mycoplasma pneumoniae infection commonly manifests as an upper or lower respiratory tract infection with associated fever, dyspnea, cough, and coryza. However, patients can present with extrapulmonary complications with dermatologic findings including mucocutaneous eruptions. M. pneumoniae–associated mucocutaneous disease has prominent mucositis and typically sparse cutaneous involvement. The mucositis usually involves the lips and oral mucosa, eye conjunctivae, and nasal mucosa and can involve urogenital lesions. It predominantly is observed in children and adolescents. This condition is essentially a subtype of Stevens-Johnson syndrome, with a specific infection-associated etiology, and has been called “Mycoplasma pneumoniae–induced rash and mucositis,” shortened to “MIRM.”

Severe reactive mucocutaneous eruptions include erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). While there has been semantic confusion over the years, there are some distinctive characteristics.

EM is characterized by typical three-ringed target papules that are predominantly acral in location and often without mucosal involvement. The lesions are “multiforme” in that they can appear polymorphous and evolve during an episode, with erythematous macules progressing to edematous papules, sometimes with a halo of pallor and concentric “target-like” appearance. Lesions of EM are fixed, meaning individual lesions last 7-10 days, unlike urticarial lesions that last hours. EM classically is associated with herpes simplex virus infections which usually precede its development.

SJS and TEN display atypical macules and papules which develop into erythematous vesicles, bullae, and potentially extensive desquamation, usually presenting with fever and systemic symptoms, with multiple mucosal sites involved. SJS usually is defined by having bullae restricted to less than 10% of body surface area (BSA), TEN as greater than 30% BSA, and “overlap SJS-TEN” as 20%-30% skin detachment.¹ SJS and TEN commonly are induced by medications and on a spectrum of drug hypersensitivity–induced epidermal necrolysis.

MIRM has been highlighted as a distinct, common condition, usually mucous-membrane predominant with involvement of two or more mucosal sites, less than 10% total BSA, the presence of few vesiculobullous lesions or scattered atypical targets with or without targetoid lesions (without rash is called MIRM sine rash), and clinical and laboratory evidence of atypical pneumonia.² Other infections can cause similar eruptions (for example, Chlamydia pneumoniae), and a recent proposal by the Pediatric Dermatology Research Alliance has suggested the term “Reactive Infectious Mucocutaneous Eruption” (RIME) to include MIRM and other infection-induced reactions.

Laboratory diagnosis of M. pneumoniae is via serology or polymerase chain reaction. Antibody titers begin to rise approximately 7-9 days after infection and peak at 3-4 weeks. Enzyme immunoassay is more sensitive in detecting acute infection than culture and has sensitivity comparable to the polymerase chain reaction if there has been sufficient time to develop an antibody response.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. Dr. Bhatti is a research fellow in pediatric dermatology at Rady Children’s Hospital and the University of California, San Diego. They said they have no financial disclosures. Email Dr. Eichenfield and Dr. Bhatti at [email protected].

References

1. Arch Dermatol. 1993 Jan;129(1):92-6.

2. J Am Acad Dermatol. 2015 Feb;72(2):239-45.

Mycoplasma pneumoniae infection commonly manifests as an upper or lower respiratory tract infection with associated fever, dyspnea, cough, and coryza. However, patients can present with extrapulmonary complications with dermatologic findings including mucocutaneous eruptions. M. pneumoniae–associated mucocutaneous disease has prominent mucositis and typically sparse cutaneous involvement. The mucositis usually involves the lips and oral mucosa, eye conjunctivae, and nasal mucosa and can involve urogenital lesions. It predominantly is observed in children and adolescents. This condition is essentially a subtype of Stevens-Johnson syndrome, with a specific infection-associated etiology, and has been called “Mycoplasma pneumoniae–induced rash and mucositis,” shortened to “MIRM.”

Severe reactive mucocutaneous eruptions include erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). While there has been semantic confusion over the years, there are some distinctive characteristics.

EM is characterized by typical three-ringed target papules that are predominantly acral in location and often without mucosal involvement. The lesions are “multiforme” in that they can appear polymorphous and evolve during an episode, with erythematous macules progressing to edematous papules, sometimes with a halo of pallor and concentric “target-like” appearance. Lesions of EM are fixed, meaning individual lesions last 7-10 days, unlike urticarial lesions that last hours. EM classically is associated with herpes simplex virus infections which usually precede its development.

SJS and TEN display atypical macules and papules which develop into erythematous vesicles, bullae, and potentially extensive desquamation, usually presenting with fever and systemic symptoms, with multiple mucosal sites involved. SJS usually is defined by having bullae restricted to less than 10% of body surface area (BSA), TEN as greater than 30% BSA, and “overlap SJS-TEN” as 20%-30% skin detachment.¹ SJS and TEN commonly are induced by medications and on a spectrum of drug hypersensitivity–induced epidermal necrolysis.

MIRM has been highlighted as a distinct, common condition, usually mucous-membrane predominant with involvement of two or more mucosal sites, less than 10% total BSA, the presence of few vesiculobullous lesions or scattered atypical targets with or without targetoid lesions (without rash is called MIRM sine rash), and clinical and laboratory evidence of atypical pneumonia.² Other infections can cause similar eruptions (for example, Chlamydia pneumoniae), and a recent proposal by the Pediatric Dermatology Research Alliance has suggested the term “Reactive Infectious Mucocutaneous Eruption” (RIME) to include MIRM and other infection-induced reactions.

Laboratory diagnosis of M. pneumoniae is via serology or polymerase chain reaction. Antibody titers begin to rise approximately 7-9 days after infection and peak at 3-4 weeks. Enzyme immunoassay is more sensitive in detecting acute infection than culture and has sensitivity comparable to the polymerase chain reaction if there has been sufficient time to develop an antibody response.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. Dr. Bhatti is a research fellow in pediatric dermatology at Rady Children’s Hospital and the University of California, San Diego. They said they have no financial disclosures. Email Dr. Eichenfield and Dr. Bhatti at [email protected].

References

1. Arch Dermatol. 1993 Jan;129(1):92-6.

2. J Am Acad Dermatol. 2015 Feb;72(2):239-45.

The use of four antibiotic classes designated “high risk” was found to be an independent predictor of hospital-acquired Clostridioides difficile (CDI), based upon an analysis of microbiologic and pharmacy data from 171 hospitals in the United States.

Andrei Malov/Thinkstock

The high-risk antibiotic classes were second-, third-, and fourth-generation cephalosporins, fluoroquinolones, carbapenems, and lincosamides, according to a report by Ying P. Tabak, PhD, of Becton Dickinson in Franklin Lakes, N.J., and colleagues published in Infection Control & Hospital Epidemiology.

Of the 171 study sites studied, 66 (39%) were teaching hospitals and 105 (61%) were nonteaching hospitals. The high-risk antibiotics most frequently used were cephalosporins (47.9%), fluoroquinolones (31.6%), carbapenems (13.0%), and lincosamides (7.6%). The sites were distributed across various regions of the United States. The hospital-level antibiotic use was measured as days of therapy (DOT) per 1,000 days present (DP).

The study was not able to determine specific links to individual antibiotic classes but to the use of high-risk antibiotics as a whole, except for cephalosporins, which were significantly correlated with hospital-acquired CDI (r = 0.23; P less than .01).

The overall correlation of high-risk antibiotic use and hospital-acquired CDI was 0.22 (P = .003). Higher correlation was observed in teaching hospitals (r = 0.38; P = .002) versus nonteaching hospitals (r = 0.19; P = .055), according to the researchers. The authors attributed this to the possibility of teaching hospitals dealing with more elderly and sicker patients.

After adjusting for significant confounders, the use of high-risk antibiotics was still independently associated with significant risk for hospital-acquired CDI. “For every 100-day increase of DOT per 1,000 DP in high-risk antibiotic use, there was a 12% increase in [hospital-acquired] CDI (RR, 1.12; 95% [confidence interval], 1.04-1.21; P = .002),” according to the authors. This translated to four additional hospital-acquired CDI cases with every 100 DOT increase per 1,000 DP.

“Using a large and current dataset, we found an independent impact of hospital-level high-risk antibiotic use on [hospital-acquired] CDI even after adjusting for confounding factors such as community CDI pressure, proportion of patients aged 65 years or older, average length of stay, and hospital teaching status,” the researchers concluded.

Funding was provided by Nabriva Therapeutics, an antibiotic development company. Four of the authors are full-time employees of Becton Dickinson, which sells diagnostics for infectious diseases, including CDI, and one author was an employee of Nabriva Therapeutics.

[email protected]

SOURCE: Tabak YP et al. Infect Control Hosp Epidemiol. 2019 Sep 16. doi: 10.1017/ice.2019.236.

The use of four antibiotic classes designated “high risk” was found to be an independent predictor of hospital-acquired Clostridioides difficile (CDI), based upon an analysis of microbiologic and pharmacy data from 171 hospitals in the United States.

Andrei Malov/Thinkstock

The high-risk antibiotic classes were second-, third-, and fourth-generation cephalosporins, fluoroquinolones, carbapenems, and lincosamides, according to a report by Ying P. Tabak, PhD, of Becton Dickinson in Franklin Lakes, N.J., and colleagues published in Infection Control & Hospital Epidemiology.

Of the 171 study sites studied, 66 (39%) were teaching hospitals and 105 (61%) were nonteaching hospitals. The high-risk antibiotics most frequently used were cephalosporins (47.9%), fluoroquinolones (31.6%), carbapenems (13.0%), and lincosamides (7.6%). The sites were distributed across various regions of the United States. The hospital-level antibiotic use was measured as days of therapy (DOT) per 1,000 days present (DP).

The study was not able to determine specific links to individual antibiotic classes but to the use of high-risk antibiotics as a whole, except for cephalosporins, which were significantly correlated with hospital-acquired CDI (r = 0.23; P less than .01).

The overall correlation of high-risk antibiotic use and hospital-acquired CDI was 0.22 (P = .003). Higher correlation was observed in teaching hospitals (r = 0.38; P = .002) versus nonteaching hospitals (r = 0.19; P = .055), according to the researchers. The authors attributed this to the possibility of teaching hospitals dealing with more elderly and sicker patients.

After adjusting for significant confounders, the use of high-risk antibiotics was still independently associated with significant risk for hospital-acquired CDI. “For every 100-day increase of DOT per 1,000 DP in high-risk antibiotic use, there was a 12% increase in [hospital-acquired] CDI (RR, 1.12; 95% [confidence interval], 1.04-1.21; P = .002),” according to the authors. This translated to four additional hospital-acquired CDI cases with every 100 DOT increase per 1,000 DP.

“Using a large and current dataset, we found an independent impact of hospital-level high-risk antibiotic use on [hospital-acquired] CDI even after adjusting for confounding factors such as community CDI pressure, proportion of patients aged 65 years or older, average length of stay, and hospital teaching status,” the researchers concluded.

Funding was provided by Nabriva Therapeutics, an antibiotic development company. Four of the authors are full-time employees of Becton Dickinson, which sells diagnostics for infectious diseases, including CDI, and one author was an employee of Nabriva Therapeutics.

[email protected]

SOURCE: Tabak YP et al. Infect Control Hosp Epidemiol. 2019 Sep 16. doi: 10.1017/ice.2019.236.

The use of four antibiotic classes designated “high risk” was found to be an independent predictor of hospital-acquired Clostridioides difficile (CDI), based upon an analysis of microbiologic and pharmacy data from 171 hospitals in the United States.

Andrei Malov/Thinkstock

The high-risk antibiotic classes were second-, third-, and fourth-generation cephalosporins, fluoroquinolones, carbapenems, and lincosamides, according to a report by Ying P. Tabak, PhD, of Becton Dickinson in Franklin Lakes, N.J., and colleagues published in Infection Control & Hospital Epidemiology.

Of the 171 study sites studied, 66 (39%) were teaching hospitals and 105 (61%) were nonteaching hospitals. The high-risk antibiotics most frequently used were cephalosporins (47.9%), fluoroquinolones (31.6%), carbapenems (13.0%), and lincosamides (7.6%). The sites were distributed across various regions of the United States. The hospital-level antibiotic use was measured as days of therapy (DOT) per 1,000 days present (DP).

The study was not able to determine specific links to individual antibiotic classes but to the use of high-risk antibiotics as a whole, except for cephalosporins, which were significantly correlated with hospital-acquired CDI (r = 0.23; P less than .01).

The overall correlation of high-risk antibiotic use and hospital-acquired CDI was 0.22 (P = .003). Higher correlation was observed in teaching hospitals (r = 0.38; P = .002) versus nonteaching hospitals (r = 0.19; P = .055), according to the researchers. The authors attributed this to the possibility of teaching hospitals dealing with more elderly and sicker patients.

After adjusting for significant confounders, the use of high-risk antibiotics was still independently associated with significant risk for hospital-acquired CDI. “For every 100-day increase of DOT per 1,000 DP in high-risk antibiotic use, there was a 12% increase in [hospital-acquired] CDI (RR, 1.12; 95% [confidence interval], 1.04-1.21; P = .002),” according to the authors. This translated to four additional hospital-acquired CDI cases with every 100 DOT increase per 1,000 DP.

“Using a large and current dataset, we found an independent impact of hospital-level high-risk antibiotic use on [hospital-acquired] CDI even after adjusting for confounding factors such as community CDI pressure, proportion of patients aged 65 years or older, average length of stay, and hospital teaching status,” the researchers concluded.

Funding was provided by Nabriva Therapeutics, an antibiotic development company. Four of the authors are full-time employees of Becton Dickinson, which sells diagnostics for infectious diseases, including CDI, and one author was an employee of Nabriva Therapeutics.

[email protected]

SOURCE: Tabak YP et al. Infect Control Hosp Epidemiol. 2019 Sep 16. doi: 10.1017/ice.2019.236.

A majority of primary care physicians recommended the human papillomavirus (HPV) vaccine to children aged 11-12 years and older, and about half of them used a presumptive style to recommend the vaccine, based on survey responses from 530 clinicians.

“Because of the crucial role of provider recommendation in parental decisions to vaccinate, a great deal of research and intervention efforts have been focused on improving provider communication regarding HPV vaccination,” Allison Kempe, MD, of the University of Colorado and Children’s Hospital Colorado, Aurora, and her colleagues wrote in Pediatrics.

“A presumptive style of initiating HPV vaccine discussions uses words that convey an assumption of vaccination and does not discuss the HPV vaccine in a different manner than other adolescent vaccines,” the authors explained. By contrast, “a conversational style engages parents in an open-ended discussion about the HPV vaccine without linguistic presupposition of vaccination.” Findings from multiple studies have shown that the presumptive approach is associated with higher acceptance of the HPV vaccine, compared with the conversational approach.

The researchers examined survey responses from a nationally representative sample of 302 pediatricians and 228 family physicians. Almost all clinicians in both specialties (99% of pediatricians, 90% of FPs) said they strongly recommended the HPV vaccine for girls aged 15 years and older. Strong recommendations for the HPV vaccine were lowest in both specialties for boys aged 11-12 years (83% of pediatricians, 66% of FPs).

Significantly more pediatricians than FPs reported using a presumptive style when discussing the HPV vaccine (65% vs. 42%, respectively; P <.0001). Overall, 40% of the survey respondents used standing orders for HPV vaccination and 42% had electronic alerts in patients’ medical records to prompt an HPV vaccine discussion.

The proportion of pediatricians who reported a vaccine refusal or deferral rate of 50% or higher for patients aged 11-12 years was 10% for girls and 23% for boys; among FPs, those percentages were 27% for girls and 36% for boys.

In multivariate analysis, the factors associated with a 50% or higher refusal or deferral rate among 11- to 12-year-olds were similar for both genders and included “not strongly recommending [the vaccine] to 11- to 12-year-old patients, not … always using a presumptive recommendation style, strongly agreeing that they encounter less resistance to HPV vaccination from patients aged 13 years versus patients aged 11 years, and anticipating an uncomfortable discussion when recommending to 11- to 12-year-old patients,” the researchers wrote.

More physicians in both specialties made stronger recommendations for HPV vaccination for patients aged 13 years and older than for those aged 11 and 12 years. However, physicians might overestimate parent and patient resistance to a strong recommendation for the HPV vaccine. A strong recommendation, “delivered in the same way as for other adolescent vaccines and on same day as other adolescent vaccines, may be key to increasing acceptance among parents of 11- to 12-year-old patients,” Dr. Kempe and associates said.

The current two-dose vaccine schedule also promoted complete vaccination, according to a majority of pediatricians and FPs.

The study findings were limited by several factors, including the use of self-reports and the potential lack of generalizability of the survey responses. The results, however, were strengthened by the large, nationally representative sample and suggest that the number of physicians who strongly recommend HPV vaccination to 11- and 12-year-olds has increased over the past 5 years, they said.

“Increased use of available communication training materials and applications, as well as further development of evidence-based messages for parents, may be helpful in improving the way HPV is introduced,” the investigators concluded.

The study was supported by the Centers for Disease Control and Prevention. The researchers reported that they had no financial conflicts.

SOURCE: Kempe A et al. Pediatrics. 2019 Sep 16. doi: 10.1542/peds.2019-1475.

A majority of primary care physicians recommended the human papillomavirus (HPV) vaccine to children aged 11-12 years and older, and about half of them used a presumptive style to recommend the vaccine, based on survey responses from 530 clinicians.

“Because of the crucial role of provider recommendation in parental decisions to vaccinate, a great deal of research and intervention efforts have been focused on improving provider communication regarding HPV vaccination,” Allison Kempe, MD, of the University of Colorado and Children’s Hospital Colorado, Aurora, and her colleagues wrote in Pediatrics.

“A presumptive style of initiating HPV vaccine discussions uses words that convey an assumption of vaccination and does not discuss the HPV vaccine in a different manner than other adolescent vaccines,” the authors explained. By contrast, “a conversational style engages parents in an open-ended discussion about the HPV vaccine without linguistic presupposition of vaccination.” Findings from multiple studies have shown that the presumptive approach is associated with higher acceptance of the HPV vaccine, compared with the conversational approach.

The researchers examined survey responses from a nationally representative sample of 302 pediatricians and 228 family physicians. Almost all clinicians in both specialties (99% of pediatricians, 90% of FPs) said they strongly recommended the HPV vaccine for girls aged 15 years and older. Strong recommendations for the HPV vaccine were lowest in both specialties for boys aged 11-12 years (83% of pediatricians, 66% of FPs).

Significantly more pediatricians than FPs reported using a presumptive style when discussing the HPV vaccine (65% vs. 42%, respectively; P <.0001). Overall, 40% of the survey respondents used standing orders for HPV vaccination and 42% had electronic alerts in patients’ medical records to prompt an HPV vaccine discussion.

The proportion of pediatricians who reported a vaccine refusal or deferral rate of 50% or higher for patients aged 11-12 years was 10% for girls and 23% for boys; among FPs, those percentages were 27% for girls and 36% for boys.

In multivariate analysis, the factors associated with a 50% or higher refusal or deferral rate among 11- to 12-year-olds were similar for both genders and included “not strongly recommending [the vaccine] to 11- to 12-year-old patients, not … always using a presumptive recommendation style, strongly agreeing that they encounter less resistance to HPV vaccination from patients aged 13 years versus patients aged 11 years, and anticipating an uncomfortable discussion when recommending to 11- to 12-year-old patients,” the researchers wrote.

More physicians in both specialties made stronger recommendations for HPV vaccination for patients aged 13 years and older than for those aged 11 and 12 years. However, physicians might overestimate parent and patient resistance to a strong recommendation for the HPV vaccine. A strong recommendation, “delivered in the same way as for other adolescent vaccines and on same day as other adolescent vaccines, may be key to increasing acceptance among parents of 11- to 12-year-old patients,” Dr. Kempe and associates said.

The current two-dose vaccine schedule also promoted complete vaccination, according to a majority of pediatricians and FPs.

The study findings were limited by several factors, including the use of self-reports and the potential lack of generalizability of the survey responses. The results, however, were strengthened by the large, nationally representative sample and suggest that the number of physicians who strongly recommend HPV vaccination to 11- and 12-year-olds has increased over the past 5 years, they said.

“Increased use of available communication training materials and applications, as well as further development of evidence-based messages for parents, may be helpful in improving the way HPV is introduced,” the investigators concluded.

The study was supported by the Centers for Disease Control and Prevention. The researchers reported that they had no financial conflicts.

SOURCE: Kempe A et al. Pediatrics. 2019 Sep 16. doi: 10.1542/peds.2019-1475.

A majority of primary care physicians recommended the human papillomavirus (HPV) vaccine to children aged 11-12 years and older, and about half of them used a presumptive style to recommend the vaccine, based on survey responses from 530 clinicians.

“Because of the crucial role of provider recommendation in parental decisions to vaccinate, a great deal of research and intervention efforts have been focused on improving provider communication regarding HPV vaccination,” Allison Kempe, MD, of the University of Colorado and Children’s Hospital Colorado, Aurora, and her colleagues wrote in Pediatrics.

“A presumptive style of initiating HPV vaccine discussions uses words that convey an assumption of vaccination and does not discuss the HPV vaccine in a different manner than other adolescent vaccines,” the authors explained. By contrast, “a conversational style engages parents in an open-ended discussion about the HPV vaccine without linguistic presupposition of vaccination.” Findings from multiple studies have shown that the presumptive approach is associated with higher acceptance of the HPV vaccine, compared with the conversational approach.

The researchers examined survey responses from a nationally representative sample of 302 pediatricians and 228 family physicians. Almost all clinicians in both specialties (99% of pediatricians, 90% of FPs) said they strongly recommended the HPV vaccine for girls aged 15 years and older. Strong recommendations for the HPV vaccine were lowest in both specialties for boys aged 11-12 years (83% of pediatricians, 66% of FPs).

Significantly more pediatricians than FPs reported using a presumptive style when discussing the HPV vaccine (65% vs. 42%, respectively; P <.0001). Overall, 40% of the survey respondents used standing orders for HPV vaccination and 42% had electronic alerts in patients’ medical records to prompt an HPV vaccine discussion.

The proportion of pediatricians who reported a vaccine refusal or deferral rate of 50% or higher for patients aged 11-12 years was 10% for girls and 23% for boys; among FPs, those percentages were 27% for girls and 36% for boys.

In multivariate analysis, the factors associated with a 50% or higher refusal or deferral rate among 11- to 12-year-olds were similar for both genders and included “not strongly recommending [the vaccine] to 11- to 12-year-old patients, not … always using a presumptive recommendation style, strongly agreeing that they encounter less resistance to HPV vaccination from patients aged 13 years versus patients aged 11 years, and anticipating an uncomfortable discussion when recommending to 11- to 12-year-old patients,” the researchers wrote.

More physicians in both specialties made stronger recommendations for HPV vaccination for patients aged 13 years and older than for those aged 11 and 12 years. However, physicians might overestimate parent and patient resistance to a strong recommendation for the HPV vaccine. A strong recommendation, “delivered in the same way as for other adolescent vaccines and on same day as other adolescent vaccines, may be key to increasing acceptance among parents of 11- to 12-year-old patients,” Dr. Kempe and associates said.

The current two-dose vaccine schedule also promoted complete vaccination, according to a majority of pediatricians and FPs.

The study findings were limited by several factors, including the use of self-reports and the potential lack of generalizability of the survey responses. The results, however, were strengthened by the large, nationally representative sample and suggest that the number of physicians who strongly recommend HPV vaccination to 11- and 12-year-olds has increased over the past 5 years, they said.

“Increased use of available communication training materials and applications, as well as further development of evidence-based messages for parents, may be helpful in improving the way HPV is introduced,” the investigators concluded.

The study was supported by the Centers for Disease Control and Prevention. The researchers reported that they had no financial conflicts.

SOURCE: Kempe A et al. Pediatrics. 2019 Sep 16. doi: 10.1542/peds.2019-1475.

Pharmacist-led intervention reduced inappropriate medication prescriptions

An outpatient pharmacy-led intervention of notifying prescribing physicians to discontinue inappropriate Beers Criteria medications resulted in a greater discontinuation of inappropriate medications for older adults at 6 months, compared with the control group (43% vs. 12% discontinuation).

Citation: Martin P et al. Effect of a pharmacist-led educational intervention on inappropriate medication prescriptions in older adults: The D-PRESCRIBE randomized clinical trial. JAMA. 2018;320(18):1889-98.

Omadacycline noninferior for community-acquired pneumonia and acute bacterial soft tissue skin infections

Randomized, double-blind, double-dummy trials showed omadacycline is a noninferior alternative to moxifloxacin for the treatment of community-acquired pneumonia and to linezolid for acute bacterial soft-tissue skin infections.

Citation: Nuzyra (omadacycline) [package insert]. Boston, MA: Paratek Pharmaceuticals. 2018.

Lack of evidence to support low-salt diet in adult heart failure patients

Systematic review of multiple databases demonstrated there is limited high-quality evidence to support current guidelines that recommend a low-salt diet to heart failure patients.

Citation: Mahtani KR et al. Reduced salt intake for heart failure: A systematic review. JAMA Int Med. 2018;178(12):1693-700.

Magnesium for rate control in rapid atrial fibrillation

Randomized, controlled trial demonstrated that intravenous magnesium sulfate in combination with atrioventricular (AV) nodal blocking agents resulted in better rate control for atrial fibrillation with rapid ventricular response than did placebo given in combination with AV nodal blocking agents.

Citation: Bouida W et al. Low-dose magnesium sulfate versus high-dose in the early management of rapid atrial fibrillation: Randomized controlled double-blind study (LOMAGHI Study). Acad Emerg Med. 2019 Feb;26(2):183-91.

Low versus intermediate tidal volume strategy on ventilator-free days in ICU patients without ARDS

Randomized, clinical trial of low tidal volume versus intermediate tidal volume strategies in invasively ventilated patients without accute respiratory distress syndrome (ARDS) demonstrated no difference in number of ventilator-free days, ICU length of stay, hospital length of stay, incidence of ventilator-associated adverse events (ARDS, pneumonia, severe atelectasis, pneumothorax), or 28-day mortality.

Citation: Writing Group for the PReVENT Investigators, Simonis FD, Serpa Neto A. Effect of a low vs intermediate tidal volume strategy on ventilator-free days in intensive care unit patients without ARDS: A randomized clinical trial. JAMA. 2018;320(18):1872-80.

Pharmacist-led intervention reduced inappropriate medication prescriptions

An outpatient pharmacy-led intervention of notifying prescribing physicians to discontinue inappropriate Beers Criteria medications resulted in a greater discontinuation of inappropriate medications for older adults at 6 months, compared with the control group (43% vs. 12% discontinuation).

Citation: Martin P et al. Effect of a pharmacist-led educational intervention on inappropriate medication prescriptions in older adults: The D-PRESCRIBE randomized clinical trial. JAMA. 2018;320(18):1889-98.

Omadacycline noninferior for community-acquired pneumonia and acute bacterial soft tissue skin infections

Randomized, double-blind, double-dummy trials showed omadacycline is a noninferior alternative to moxifloxacin for the treatment of community-acquired pneumonia and to linezolid for acute bacterial soft-tissue skin infections.

Citation: Nuzyra (omadacycline) [package insert]. Boston, MA: Paratek Pharmaceuticals. 2018.

Lack of evidence to support low-salt diet in adult heart failure patients

Systematic review of multiple databases demonstrated there is limited high-quality evidence to support current guidelines that recommend a low-salt diet to heart failure patients.

Citation: Mahtani KR et al. Reduced salt intake for heart failure: A systematic review. JAMA Int Med. 2018;178(12):1693-700.

Magnesium for rate control in rapid atrial fibrillation

Randomized, controlled trial demonstrated that intravenous magnesium sulfate in combination with atrioventricular (AV) nodal blocking agents resulted in better rate control for atrial fibrillation with rapid ventricular response than did placebo given in combination with AV nodal blocking agents.

Citation: Bouida W et al. Low-dose magnesium sulfate versus high-dose in the early management of rapid atrial fibrillation: Randomized controlled double-blind study (LOMAGHI Study). Acad Emerg Med. 2019 Feb;26(2):183-91.

Low versus intermediate tidal volume strategy on ventilator-free days in ICU patients without ARDS

Randomized, clinical trial of low tidal volume versus intermediate tidal volume strategies in invasively ventilated patients without accute respiratory distress syndrome (ARDS) demonstrated no difference in number of ventilator-free days, ICU length of stay, hospital length of stay, incidence of ventilator-associated adverse events (ARDS, pneumonia, severe atelectasis, pneumothorax), or 28-day mortality.

Citation: Writing Group for the PReVENT Investigators, Simonis FD, Serpa Neto A. Effect of a low vs intermediate tidal volume strategy on ventilator-free days in intensive care unit patients without ARDS: A randomized clinical trial. JAMA. 2018;320(18):1872-80.

Pharmacist-led intervention reduced inappropriate medication prescriptions

An outpatient pharmacy-led intervention of notifying prescribing physicians to discontinue inappropriate Beers Criteria medications resulted in a greater discontinuation of inappropriate medications for older adults at 6 months, compared with the control group (43% vs. 12% discontinuation).

Citation: Martin P et al. Effect of a pharmacist-led educational intervention on inappropriate medication prescriptions in older adults: The D-PRESCRIBE randomized clinical trial. JAMA. 2018;320(18):1889-98.

Omadacycline noninferior for community-acquired pneumonia and acute bacterial soft tissue skin infections

Randomized, double-blind, double-dummy trials showed omadacycline is a noninferior alternative to moxifloxacin for the treatment of community-acquired pneumonia and to linezolid for acute bacterial soft-tissue skin infections.

Citation: Nuzyra (omadacycline) [package insert]. Boston, MA: Paratek Pharmaceuticals. 2018.

Lack of evidence to support low-salt diet in adult heart failure patients

Systematic review of multiple databases demonstrated there is limited high-quality evidence to support current guidelines that recommend a low-salt diet to heart failure patients.

Citation: Mahtani KR et al. Reduced salt intake for heart failure: A systematic review. JAMA Int Med. 2018;178(12):1693-700.

Magnesium for rate control in rapid atrial fibrillation

Randomized, controlled trial demonstrated that intravenous magnesium sulfate in combination with atrioventricular (AV) nodal blocking agents resulted in better rate control for atrial fibrillation with rapid ventricular response than did placebo given in combination with AV nodal blocking agents.

Citation: Bouida W et al. Low-dose magnesium sulfate versus high-dose in the early management of rapid atrial fibrillation: Randomized controlled double-blind study (LOMAGHI Study). Acad Emerg Med. 2019 Feb;26(2):183-91.

Low versus intermediate tidal volume strategy on ventilator-free days in ICU patients without ARDS

Randomized, clinical trial of low tidal volume versus intermediate tidal volume strategies in invasively ventilated patients without accute respiratory distress syndrome (ARDS) demonstrated no difference in number of ventilator-free days, ICU length of stay, hospital length of stay, incidence of ventilator-associated adverse events (ARDS, pneumonia, severe atelectasis, pneumothorax), or 28-day mortality.

Citation: Writing Group for the PReVENT Investigators, Simonis FD, Serpa Neto A. Effect of a low vs intermediate tidal volume strategy on ventilator-free days in intensive care unit patients without ARDS: A randomized clinical trial. JAMA. 2018;320(18):1872-80.

Gene editing of donor stem cells prior to transplantation into a patient with both HIV infection and acute lymphoblastic leukemia (ALL) was safe and effectively treated the patient’s leukemia, but failed to resolve his HIV, investigators reported.

NIAID

The 27-year-old man received an HLA-matched transplant of hematopoietic stem and progenitor cells (HSPCs) that had been genetically engineered to lack CCR5, a key gateway for HIV entry into cells.

Although the transplant resulted in complete remission of leukemia with full donor chimerism, only about 9% of the posttransplant lymphocytes showed disruption of CCR5, and during a brief trial of antiretroviral therapy interruption his HIV viral load rebounded, reported Hongkui Deng, PhD, and colleagues from Peking University in China.

Although the experiment did not meet its goal of a drug-free HIV remission, it serves as a proof of concept for the use of CRISPR-Cas9 (clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9) gene editing to treat HIV infection, the authors contend.

“These results show the proof of principle that transplantation and long-term engraftment of CRISPR-edited allogeneic HSPCs can be achieved; however, the efficiency of the response was not adequate to achieve the target of cure of HIV-1 infection,” they wrote in a brief report published in the New England Journal of Medicine.

As previously reported, other research groups have investigated genetic editing to mimic a naturally occurring mutation that effectively disables the CCR5 HIV coreceptor, preventing the retrovirus from entering healthy cells. The mutation was first identified in a man named Timothy Brown who came to be known as “the Berlin patient” after he was apparently cured of HIV infection after a bone marrow transplant from a donor who had the mutation.

Dr. Deng and colleagues took advantage of HSPC transplantation, a standard therapy for ALL to see whether it could also have beneficial effects on concomitant HIV infection.

They treated donor HSPCs with CRISPR-Cas9 to ablate CCR5 and then delivered them to the patient along with additional CD34-depleted donor cells from mobilized peripheral blood.

The transplant was a success, with neutrophil engraftment on day 13 and platelet engraftment on day 27, and the leukemia was in morphologic complete remission at week 4 following transplantation. The patient remained in complete remission from leukemia throughout the 19-month follow-up period, with full donor chimerism .

However, when a planned interruption of antiretroviral therapy was carried out at 7 months post transplant, the serum viral load increased to 3 × 10⁷ copies/ml at week 4 following interruption, and the patient was restarted on the drug. His viral levels gradually decreased to undetectable level during the subsequent months.

The investigators noted that 2 weeks after the drug interruption trial was started there was a small increase in the percentage of CCR5 insertion/deletions.

“The low efficiency of gene editing in the patient may be due to the competitive engraftment of the coinfused HSPCs in CD34-depleted cells and the persistence of donor T cells. To further clarify the anti-HIV effect of CCR5-ablated HSPCs, it will be essential to increase the gene-editing efficiency of our CRISPR-Cas9 system and improve the transplantation protocol,” they wrote.

The study was funded by the Beijing Municipal Science and Technology Commission and others (unspecified). All authors reported having nothing to disclose.

SOURCE: Xu L et al. N Engl J Med. 2019. doi: 10.1056/NEJMoa1817426.

Gene editing of donor stem cells prior to transplantation into a patient with both HIV infection and acute lymphoblastic leukemia (ALL) was safe and effectively treated the patient’s leukemia, but failed to resolve his HIV, investigators reported.

NIAID

The 27-year-old man received an HLA-matched transplant of hematopoietic stem and progenitor cells (HSPCs) that had been genetically engineered to lack CCR5, a key gateway for HIV entry into cells.

Although the transplant resulted in complete remission of leukemia with full donor chimerism, only about 9% of the posttransplant lymphocytes showed disruption of CCR5, and during a brief trial of antiretroviral therapy interruption his HIV viral load rebounded, reported Hongkui Deng, PhD, and colleagues from Peking University in China.

Although the experiment did not meet its goal of a drug-free HIV remission, it serves as a proof of concept for the use of CRISPR-Cas9 (clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9) gene editing to treat HIV infection, the authors contend.

“These results show the proof of principle that transplantation and long-term engraftment of CRISPR-edited allogeneic HSPCs can be achieved; however, the efficiency of the response was not adequate to achieve the target of cure of HIV-1 infection,” they wrote in a brief report published in the New England Journal of Medicine.

As previously reported, other research groups have investigated genetic editing to mimic a naturally occurring mutation that effectively disables the CCR5 HIV coreceptor, preventing the retrovirus from entering healthy cells. The mutation was first identified in a man named Timothy Brown who came to be known as “the Berlin patient” after he was apparently cured of HIV infection after a bone marrow transplant from a donor who had the mutation.

Dr. Deng and colleagues took advantage of HSPC transplantation, a standard therapy for ALL to see whether it could also have beneficial effects on concomitant HIV infection.

They treated donor HSPCs with CRISPR-Cas9 to ablate CCR5 and then delivered them to the patient along with additional CD34-depleted donor cells from mobilized peripheral blood.

The transplant was a success, with neutrophil engraftment on day 13 and platelet engraftment on day 27, and the leukemia was in morphologic complete remission at week 4 following transplantation. The patient remained in complete remission from leukemia throughout the 19-month follow-up period, with full donor chimerism .

However, when a planned interruption of antiretroviral therapy was carried out at 7 months post transplant, the serum viral load increased to 3 × 10⁷ copies/ml at week 4 following interruption, and the patient was restarted on the drug. His viral levels gradually decreased to undetectable level during the subsequent months.

The investigators noted that 2 weeks after the drug interruption trial was started there was a small increase in the percentage of CCR5 insertion/deletions.

“The low efficiency of gene editing in the patient may be due to the competitive engraftment of the coinfused HSPCs in CD34-depleted cells and the persistence of donor T cells. To further clarify the anti-HIV effect of CCR5-ablated HSPCs, it will be essential to increase the gene-editing efficiency of our CRISPR-Cas9 system and improve the transplantation protocol,” they wrote.

The study was funded by the Beijing Municipal Science and Technology Commission and others (unspecified). All authors reported having nothing to disclose.

SOURCE: Xu L et al. N Engl J Med. 2019. doi: 10.1056/NEJMoa1817426.

Gene editing of donor stem cells prior to transplantation into a patient with both HIV infection and acute lymphoblastic leukemia (ALL) was safe and effectively treated the patient’s leukemia, but failed to resolve his HIV, investigators reported.

NIAID

The 27-year-old man received an HLA-matched transplant of hematopoietic stem and progenitor cells (HSPCs) that had been genetically engineered to lack CCR5, a key gateway for HIV entry into cells.

Although the transplant resulted in complete remission of leukemia with full donor chimerism, only about 9% of the posttransplant lymphocytes showed disruption of CCR5, and during a brief trial of antiretroviral therapy interruption his HIV viral load rebounded, reported Hongkui Deng, PhD, and colleagues from Peking University in China.

Although the experiment did not meet its goal of a drug-free HIV remission, it serves as a proof of concept for the use of CRISPR-Cas9 (clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9) gene editing to treat HIV infection, the authors contend.

“These results show the proof of principle that transplantation and long-term engraftment of CRISPR-edited allogeneic HSPCs can be achieved; however, the efficiency of the response was not adequate to achieve the target of cure of HIV-1 infection,” they wrote in a brief report published in the New England Journal of Medicine.

As previously reported, other research groups have investigated genetic editing to mimic a naturally occurring mutation that effectively disables the CCR5 HIV coreceptor, preventing the retrovirus from entering healthy cells. The mutation was first identified in a man named Timothy Brown who came to be known as “the Berlin patient” after he was apparently cured of HIV infection after a bone marrow transplant from a donor who had the mutation.

Dr. Deng and colleagues took advantage of HSPC transplantation, a standard therapy for ALL to see whether it could also have beneficial effects on concomitant HIV infection.

They treated donor HSPCs with CRISPR-Cas9 to ablate CCR5 and then delivered them to the patient along with additional CD34-depleted donor cells from mobilized peripheral blood.

The transplant was a success, with neutrophil engraftment on day 13 and platelet engraftment on day 27, and the leukemia was in morphologic complete remission at week 4 following transplantation. The patient remained in complete remission from leukemia throughout the 19-month follow-up period, with full donor chimerism .

However, when a planned interruption of antiretroviral therapy was carried out at 7 months post transplant, the serum viral load increased to 3 × 10⁷ copies/ml at week 4 following interruption, and the patient was restarted on the drug. His viral levels gradually decreased to undetectable level during the subsequent months.

The investigators noted that 2 weeks after the drug interruption trial was started there was a small increase in the percentage of CCR5 insertion/deletions.

“The low efficiency of gene editing in the patient may be due to the competitive engraftment of the coinfused HSPCs in CD34-depleted cells and the persistence of donor T cells. To further clarify the anti-HIV effect of CCR5-ablated HSPCs, it will be essential to increase the gene-editing efficiency of our CRISPR-Cas9 system and improve the transplantation protocol,” they wrote.

The study was funded by the Beijing Municipal Science and Technology Commission and others (unspecified). All authors reported having nothing to disclose.

SOURCE: Xu L et al. N Engl J Med. 2019. doi: 10.1056/NEJMoa1817426.

A new Streptococcus pyogenes genotype (designated M1_UK) emerged in 2014 in England causing an increase in scarlet fever “unprecedented in modern times.” Researchers discovered that this new genotype became dominant during this increased period of scarlet fever. This new genotype was characterized by an increased production of streptococcal pyrogenic exotoxin A (SpeA, also known as scarlet fever or erythrogenic toxin A) compared to previous isolates, according to a report in The Lancet Infectious Diseases.

CDC

[email protected]

SOURCE: Linskey NN et al. Lancet Infect Dis. 2019. doi: 10.1016/S1473-3099(19)30446-3.

A new Streptococcus pyogenes genotype (designated M1_UK) emerged in 2014 in England causing an increase in scarlet fever “unprecedented in modern times.” Researchers discovered that this new genotype became dominant during this increased period of scarlet fever. This new genotype was characterized by an increased production of streptococcal pyrogenic exotoxin A (SpeA, also known as scarlet fever or erythrogenic toxin A) compared to previous isolates, according to a report in The Lancet Infectious Diseases.

CDC

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SOURCE: Linskey NN et al. Lancet Infect Dis. 2019. doi: 10.1016/S1473-3099(19)30446-3.

A new Streptococcus pyogenes genotype (designated M1_UK) emerged in 2014 in England causing an increase in scarlet fever “unprecedented in modern times.” Researchers discovered that this new genotype became dominant during this increased period of scarlet fever. This new genotype was characterized by an increased production of streptococcal pyrogenic exotoxin A (SpeA, also known as scarlet fever or erythrogenic toxin A) compared to previous isolates, according to a report in The Lancet Infectious Diseases.

CDC

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SOURCE: Linskey NN et al. Lancet Infect Dis. 2019. doi: 10.1016/S1473-3099(19)30446-3.

The number of measles cases reported in the United States dropped for the fourth month in a row in August after reaching a peak of 341 in April, according to the Centers for Disease Control and Prevention.

A total of 24 measles cases were confirmed in August, and the total for the year is now 1,241 cases in 31 states. Only seven of those cases were added during the most recent reporting week, which ended Sept. 5, but five were older cases that had just been reported, the CDC said Sept. 9.

With the ending of the measles outbreak in New York, announced Sept. 3, the largest of the three remaining active outbreaks in the country is in Rockland County, N.Y., just north of the city, which has reported 312 cases since it began in 2018.

The two other outbreaks are located in El Paso, Tex., where six cases have been reported so far, and Wyoming County in western New York State, where five cases have occurred.

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The number of measles cases reported in the United States dropped for the fourth month in a row in August after reaching a peak of 341 in April, according to the Centers for Disease Control and Prevention.

A total of 24 measles cases were confirmed in August, and the total for the year is now 1,241 cases in 31 states. Only seven of those cases were added during the most recent reporting week, which ended Sept. 5, but five were older cases that had just been reported, the CDC said Sept. 9.

With the ending of the measles outbreak in New York, announced Sept. 3, the largest of the three remaining active outbreaks in the country is in Rockland County, N.Y., just north of the city, which has reported 312 cases since it began in 2018.

The two other outbreaks are located in El Paso, Tex., where six cases have been reported so far, and Wyoming County in western New York State, where five cases have occurred.

[email protected]

The number of measles cases reported in the United States dropped for the fourth month in a row in August after reaching a peak of 341 in April, according to the Centers for Disease Control and Prevention.

A total of 24 measles cases were confirmed in August, and the total for the year is now 1,241 cases in 31 states. Only seven of those cases were added during the most recent reporting week, which ended Sept. 5, but five were older cases that had just been reported, the CDC said Sept. 9.

With the ending of the measles outbreak in New York, announced Sept. 3, the largest of the three remaining active outbreaks in the country is in Rockland County, N.Y., just north of the city, which has reported 312 cases since it began in 2018.

The two other outbreaks are located in El Paso, Tex., where six cases have been reported so far, and Wyoming County in western New York State, where five cases have occurred.

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