Infectious Diseases

SEATTLE – Chronic obstructive pulmonary disease is independently associated with an increased risk of myocardial infarction in people with HIV, according to a report at the Conference on Retroviruses and Opportunistic Infections.

Chronic obstructive pulmonary disease (COPD) is known to increase the risk of myocardial infarction (MI) in the general population, but hadn’t been shown until now to do the same in HIV. The study raises the question of whether COPD is being managed adequately in patients with the virus, according to study lead Kristina Crothers, MD, associate professor in the division of pulmonary, critical care & sleep medicine at the University of Washington, Seattle.

The investigators reviewed 25,509 HIV patients in the Center for AIDS Research Network of Integrated Clinical Systems cohort, a large electronic database of HIV-infected people. They defined COPD by diagnostic codes and inhaler prescriptions. MIs were adjudicated by review.

The team identified 423 subjects with moderate to severe COPD, and 698 who had MIs, including 339 type 1 MIs (T1MI) from a ruptured plaque (54%), and 294 (46%) type 2 heart attacks (T2MI) from a supply-demand mismatch due to sepsis or some other problem. In general, T2MIs are far more common in people with HIV.

COPD was associated with a greater than twofold increased risk of MI after adjustment for age, sex, viral load, nadir CD4 count, hypertension, and other confounders. The risk dropped slightly when smoking – both current smoking and pack years – was added to the model (adjusted hazard ratio 1.88, 95% confidence interval, 1.34-2.63).

The association was particularly strong for T2MI, especially in the setting of bacteremia and sepsis, and unlike T1MI, it remained significant after adjustment for smoking.

The study establishes a link between COPD and MI in HIV, but it could not answer what’s going on. Chronic inflammation from the virus could be at play, but the team also found hints of inadequate COPD management.

“About 60% of patients were on inhalers ... but only about 25% of them were on long-acting inhalers. 75% were only on short-acting.” That’s a problem because long-acting inhalers are needed to control exacerbations, Dr. Crothers said.

The study didn’t capture exacerbation rates, but increased rates could help explain the MI risk. Increased rates of pneumonia could as well, since pneumonia is a common cause of sepsis.

“We need to better manage complications of COPD in this population. I think optimizing long-term COPD management could have many beneficial effects,” Dr. Crothers said.

The National Institutes of Health funded the work. Dr. Crothers had no disclosures.

[email protected]

SOURCE: Crothers K et al. CROI 2019, Abstract 31.

SEATTLE – Chronic obstructive pulmonary disease is independently associated with an increased risk of myocardial infarction in people with HIV, according to a report at the Conference on Retroviruses and Opportunistic Infections.

Chronic obstructive pulmonary disease (COPD) is known to increase the risk of myocardial infarction (MI) in the general population, but hadn’t been shown until now to do the same in HIV. The study raises the question of whether COPD is being managed adequately in patients with the virus, according to study lead Kristina Crothers, MD, associate professor in the division of pulmonary, critical care & sleep medicine at the University of Washington, Seattle.

The investigators reviewed 25,509 HIV patients in the Center for AIDS Research Network of Integrated Clinical Systems cohort, a large electronic database of HIV-infected people. They defined COPD by diagnostic codes and inhaler prescriptions. MIs were adjudicated by review.

The team identified 423 subjects with moderate to severe COPD, and 698 who had MIs, including 339 type 1 MIs (T1MI) from a ruptured plaque (54%), and 294 (46%) type 2 heart attacks (T2MI) from a supply-demand mismatch due to sepsis or some other problem. In general, T2MIs are far more common in people with HIV.

COPD was associated with a greater than twofold increased risk of MI after adjustment for age, sex, viral load, nadir CD4 count, hypertension, and other confounders. The risk dropped slightly when smoking – both current smoking and pack years – was added to the model (adjusted hazard ratio 1.88, 95% confidence interval, 1.34-2.63).

The association was particularly strong for T2MI, especially in the setting of bacteremia and sepsis, and unlike T1MI, it remained significant after adjustment for smoking.

The study establishes a link between COPD and MI in HIV, but it could not answer what’s going on. Chronic inflammation from the virus could be at play, but the team also found hints of inadequate COPD management.

“About 60% of patients were on inhalers ... but only about 25% of them were on long-acting inhalers. 75% were only on short-acting.” That’s a problem because long-acting inhalers are needed to control exacerbations, Dr. Crothers said.

The study didn’t capture exacerbation rates, but increased rates could help explain the MI risk. Increased rates of pneumonia could as well, since pneumonia is a common cause of sepsis.

“We need to better manage complications of COPD in this population. I think optimizing long-term COPD management could have many beneficial effects,” Dr. Crothers said.

The National Institutes of Health funded the work. Dr. Crothers had no disclosures.

[email protected]

SOURCE: Crothers K et al. CROI 2019, Abstract 31.

SEATTLE – Chronic obstructive pulmonary disease is independently associated with an increased risk of myocardial infarction in people with HIV, according to a report at the Conference on Retroviruses and Opportunistic Infections.

Chronic obstructive pulmonary disease (COPD) is known to increase the risk of myocardial infarction (MI) in the general population, but hadn’t been shown until now to do the same in HIV. The study raises the question of whether COPD is being managed adequately in patients with the virus, according to study lead Kristina Crothers, MD, associate professor in the division of pulmonary, critical care & sleep medicine at the University of Washington, Seattle.

The investigators reviewed 25,509 HIV patients in the Center for AIDS Research Network of Integrated Clinical Systems cohort, a large electronic database of HIV-infected people. They defined COPD by diagnostic codes and inhaler prescriptions. MIs were adjudicated by review.

The team identified 423 subjects with moderate to severe COPD, and 698 who had MIs, including 339 type 1 MIs (T1MI) from a ruptured plaque (54%), and 294 (46%) type 2 heart attacks (T2MI) from a supply-demand mismatch due to sepsis or some other problem. In general, T2MIs are far more common in people with HIV.

COPD was associated with a greater than twofold increased risk of MI after adjustment for age, sex, viral load, nadir CD4 count, hypertension, and other confounders. The risk dropped slightly when smoking – both current smoking and pack years – was added to the model (adjusted hazard ratio 1.88, 95% confidence interval, 1.34-2.63).

The association was particularly strong for T2MI, especially in the setting of bacteremia and sepsis, and unlike T1MI, it remained significant after adjustment for smoking.

The study establishes a link between COPD and MI in HIV, but it could not answer what’s going on. Chronic inflammation from the virus could be at play, but the team also found hints of inadequate COPD management.

“About 60% of patients were on inhalers ... but only about 25% of them were on long-acting inhalers. 75% were only on short-acting.” That’s a problem because long-acting inhalers are needed to control exacerbations, Dr. Crothers said.

The study didn’t capture exacerbation rates, but increased rates could help explain the MI risk. Increased rates of pneumonia could as well, since pneumonia is a common cause of sepsis.

“We need to better manage complications of COPD in this population. I think optimizing long-term COPD management could have many beneficial effects,” Dr. Crothers said.

The National Institutes of Health funded the work. Dr. Crothers had no disclosures.

[email protected]

SOURCE: Crothers K et al. CROI 2019, Abstract 31.

SAN DIEGO – Powerful antibiotics come first to mind when hospitalized patients have sepsis, but a critical care pulmonology specialist urged colleagues to consider another treatment – heavy intravenous doses of vitamin C.

“There is evidence supporting benefit, and ample evidence supporting safety,” Michael H. Hooper, MD, who practices in Norfolk, Va., said in a pro-and-con debate over the use of vitamin C in sepsis at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

Dr. Hooper’s debate opponent countered by noting the lack of quality research into vitamin C in sepsis and declared that its time has not yet come. “We need more data to know the safety of this drug,” said Andre Kalil, MD, professor of internal medicine and director of Transplant Infectious Diseases at the University of Nebraska Medical Center, Omaha.

Dr. Hooper was part of a member of a team led by Paul E. Marik, MD, FCCP, of Eastern Virginia Medical School, Norfolk, that made waves in 2017 with a study in Chest suggesting IV vitamin C has tremendous potential as a treatment for sepsis (Chest. 2017 Jun;151[6]:1229-38).

The retrospective study compared two groups of 47 patients with sepsis – a control group and a group that received treatment with intravenous vitamin C, hydrocortisone, and thiamine. Remarkably, the team found that 9% (4 of 47) of those in the treatment group died in the hospital, compared with 40% (19 of 47) in the control group (P less than .001).

The findings make sense, Dr. Hooper said, in light of the fact that “our patients are remarkably deficient” in vitamin C. He pointed to a 2017 study that found nearly 40% of 24 patients with septic shock were deficient in vitamin C – despite getting recommended enteral nutrition, parenteral nutrition or both – compared with 25% of patients who were not septic. The study authors believe the difference is probably due to “increased metabolism due to the enhanced inflammatory response observed in septic shock” (Crit Care. 2017 Dec 11;21[1]:300).

“We’re dealing with a population of patients who need some sort of repletion of this vitamin,” Dr. Hooper said.

Why not try oral administration of vitamin C? “Oral administration at regular doses doesn’t work,” he said. “If you have normal volunteers who are made deficient, then you administer the recommended allowance, it takes days or weeks to return levels to normal.”

Dr. Hooper added that the goal of vitamin C therapy isn’t simply to restore proper levels in plasma. In addition, he said, “we’re trying to restore levels in crucial organs.”

He said the cost of treatment with IV vitamin C is low, and no serious adverse events have been seen in studies of the vitamin’s use in critical care.

In his comments at the debate, Dr. Kalil pointed to several weaknesses in the 2017 study of vitamin C in sepsis. According to him, it had many problems, including a sample size that lacked statistical power and imbalances in the two groups. He raised concerns about the study in a 2017 letter published in Chest titled “Vitamin C Is Not Ready for Prime Time in Sepsis but a Solution Is Close,” noting that the control group was sicker and none of those patients had their vitamin C levels measured (Chest. 2017 Sep;152[3]:676).

Randy Dotinga/MDedge News

He added that “acute renal failure is associated with high doses of vitamin C.”

As of July 2018, several clinical trials into vitamin C, hydrocortisone, and thiamine for the treatment of septic shock were underway or planned, according to a report that described the current randomized, placebo-controlled, multicenter Ascorbic Acid, Corticosteroids, and Thiamine in Sepsis (ACTS) trial in the United States. The report notes that “robust evidence” for this approach is lacking, although “the potential effectiveness of this medication combination is rooted in biologic plausibility and supported by small clinical trials of the various individual components.” (Crit Care. 2018;22:283)

Dr. Hooper is an executive committee member and principal investigator with the Vitamin C, Thiamine And Steroids in Sepsis (VICTAS) study. Dr. Kalil reports no relevant disclosures.

SAN DIEGO – Powerful antibiotics come first to mind when hospitalized patients have sepsis, but a critical care pulmonology specialist urged colleagues to consider another treatment – heavy intravenous doses of vitamin C.

“There is evidence supporting benefit, and ample evidence supporting safety,” Michael H. Hooper, MD, who practices in Norfolk, Va., said in a pro-and-con debate over the use of vitamin C in sepsis at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

Dr. Hooper’s debate opponent countered by noting the lack of quality research into vitamin C in sepsis and declared that its time has not yet come. “We need more data to know the safety of this drug,” said Andre Kalil, MD, professor of internal medicine and director of Transplant Infectious Diseases at the University of Nebraska Medical Center, Omaha.

Dr. Hooper was part of a member of a team led by Paul E. Marik, MD, FCCP, of Eastern Virginia Medical School, Norfolk, that made waves in 2017 with a study in Chest suggesting IV vitamin C has tremendous potential as a treatment for sepsis (Chest. 2017 Jun;151[6]:1229-38).

The retrospective study compared two groups of 47 patients with sepsis – a control group and a group that received treatment with intravenous vitamin C, hydrocortisone, and thiamine. Remarkably, the team found that 9% (4 of 47) of those in the treatment group died in the hospital, compared with 40% (19 of 47) in the control group (P less than .001).

The findings make sense, Dr. Hooper said, in light of the fact that “our patients are remarkably deficient” in vitamin C. He pointed to a 2017 study that found nearly 40% of 24 patients with septic shock were deficient in vitamin C – despite getting recommended enteral nutrition, parenteral nutrition or both – compared with 25% of patients who were not septic. The study authors believe the difference is probably due to “increased metabolism due to the enhanced inflammatory response observed in septic shock” (Crit Care. 2017 Dec 11;21[1]:300).

“We’re dealing with a population of patients who need some sort of repletion of this vitamin,” Dr. Hooper said.

Why not try oral administration of vitamin C? “Oral administration at regular doses doesn’t work,” he said. “If you have normal volunteers who are made deficient, then you administer the recommended allowance, it takes days or weeks to return levels to normal.”

Dr. Hooper added that the goal of vitamin C therapy isn’t simply to restore proper levels in plasma. In addition, he said, “we’re trying to restore levels in crucial organs.”

He said the cost of treatment with IV vitamin C is low, and no serious adverse events have been seen in studies of the vitamin’s use in critical care.

In his comments at the debate, Dr. Kalil pointed to several weaknesses in the 2017 study of vitamin C in sepsis. According to him, it had many problems, including a sample size that lacked statistical power and imbalances in the two groups. He raised concerns about the study in a 2017 letter published in Chest titled “Vitamin C Is Not Ready for Prime Time in Sepsis but a Solution Is Close,” noting that the control group was sicker and none of those patients had their vitamin C levels measured (Chest. 2017 Sep;152[3]:676).

Randy Dotinga/MDedge News

He added that “acute renal failure is associated with high doses of vitamin C.”

As of July 2018, several clinical trials into vitamin C, hydrocortisone, and thiamine for the treatment of septic shock were underway or planned, according to a report that described the current randomized, placebo-controlled, multicenter Ascorbic Acid, Corticosteroids, and Thiamine in Sepsis (ACTS) trial in the United States. The report notes that “robust evidence” for this approach is lacking, although “the potential effectiveness of this medication combination is rooted in biologic plausibility and supported by small clinical trials of the various individual components.” (Crit Care. 2018;22:283)

Dr. Hooper is an executive committee member and principal investigator with the Vitamin C, Thiamine And Steroids in Sepsis (VICTAS) study. Dr. Kalil reports no relevant disclosures.

SAN DIEGO – Powerful antibiotics come first to mind when hospitalized patients have sepsis, but a critical care pulmonology specialist urged colleagues to consider another treatment – heavy intravenous doses of vitamin C.

“There is evidence supporting benefit, and ample evidence supporting safety,” Michael H. Hooper, MD, who practices in Norfolk, Va., said in a pro-and-con debate over the use of vitamin C in sepsis at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

Dr. Hooper’s debate opponent countered by noting the lack of quality research into vitamin C in sepsis and declared that its time has not yet come. “We need more data to know the safety of this drug,” said Andre Kalil, MD, professor of internal medicine and director of Transplant Infectious Diseases at the University of Nebraska Medical Center, Omaha.

Dr. Hooper was part of a member of a team led by Paul E. Marik, MD, FCCP, of Eastern Virginia Medical School, Norfolk, that made waves in 2017 with a study in Chest suggesting IV vitamin C has tremendous potential as a treatment for sepsis (Chest. 2017 Jun;151[6]:1229-38).

The retrospective study compared two groups of 47 patients with sepsis – a control group and a group that received treatment with intravenous vitamin C, hydrocortisone, and thiamine. Remarkably, the team found that 9% (4 of 47) of those in the treatment group died in the hospital, compared with 40% (19 of 47) in the control group (P less than .001).

The findings make sense, Dr. Hooper said, in light of the fact that “our patients are remarkably deficient” in vitamin C. He pointed to a 2017 study that found nearly 40% of 24 patients with septic shock were deficient in vitamin C – despite getting recommended enteral nutrition, parenteral nutrition or both – compared with 25% of patients who were not septic. The study authors believe the difference is probably due to “increased metabolism due to the enhanced inflammatory response observed in septic shock” (Crit Care. 2017 Dec 11;21[1]:300).

“We’re dealing with a population of patients who need some sort of repletion of this vitamin,” Dr. Hooper said.

Why not try oral administration of vitamin C? “Oral administration at regular doses doesn’t work,” he said. “If you have normal volunteers who are made deficient, then you administer the recommended allowance, it takes days or weeks to return levels to normal.”

Dr. Hooper added that the goal of vitamin C therapy isn’t simply to restore proper levels in plasma. In addition, he said, “we’re trying to restore levels in crucial organs.”

He said the cost of treatment with IV vitamin C is low, and no serious adverse events have been seen in studies of the vitamin’s use in critical care.

In his comments at the debate, Dr. Kalil pointed to several weaknesses in the 2017 study of vitamin C in sepsis. According to him, it had many problems, including a sample size that lacked statistical power and imbalances in the two groups. He raised concerns about the study in a 2017 letter published in Chest titled “Vitamin C Is Not Ready for Prime Time in Sepsis but a Solution Is Close,” noting that the control group was sicker and none of those patients had their vitamin C levels measured (Chest. 2017 Sep;152[3]:676).

Randy Dotinga/MDedge News

He added that “acute renal failure is associated with high doses of vitamin C.”

As of July 2018, several clinical trials into vitamin C, hydrocortisone, and thiamine for the treatment of septic shock were underway or planned, according to a report that described the current randomized, placebo-controlled, multicenter Ascorbic Acid, Corticosteroids, and Thiamine in Sepsis (ACTS) trial in the United States. The report notes that “robust evidence” for this approach is lacking, although “the potential effectiveness of this medication combination is rooted in biologic plausibility and supported by small clinical trials of the various individual components.” (Crit Care. 2018;22:283)

Dr. Hooper is an executive committee member and principal investigator with the Vitamin C, Thiamine And Steroids in Sepsis (VICTAS) study. Dr. Kalil reports no relevant disclosures.

SNOWMASS, COLO. – Infective endocarditis in 2019 is very different from the disease most physicians encountered in training, both in terms of epidemiology and clinical presentation, Patrick T. O’Gara, MD, observed at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

Bruce Jancin/MDedge News

The classic description of infective endocarditis provided by Sir William Osler, MD, was of a subacute bacterial infection characterized by a long latent phase of low-grade fever, back pain, weight loss, and night sweats. It was mainly a right-heart disease of younger individuals with an infected native valve, and the predominant pathogens were streptococci, Dr. O’Gara said.

“I think in the current era endocarditis is more often characterized by an acute illness with toxic features in the context of adults with a high burden of degenerative diseases – for example, patients with rheumatoid arthritis or psoriatic arthritis on immunosuppressive therapy, or diabetes, end-stage renal disease, and risk factors for hospital-acquired infection. Injectable drug use is through the roof, there’s a wider prevalence of cardiac implanted electronic devices, which are a wonderful place for bacteria to hide, and Staphylococcus aureus has certainly become the leading pathogen with regard to endocarditis in the United States, especially MRSA, often multidrug resistant,” said Dr. O’Gara, professor of medicine at Harvard Medical School, Boston.

“Also, no talk about endocarditis is sufficient without paying some attention to the opioid crisis in which we find ourselves. It’s one of the top three causes of death among young men in the United States, along with accidents and gun violence. No region of the country is spared. This has completely inundated our ER and hospitalist services and our inpatient cardiology services with folks who are often repeat offenders when it comes to the difficulty in being able to give up an injectable drug use habit. They have multiple infections and hospitalizations, tricuspid valve involvement, and depending upon the aggressiveness of the Staphylococcus organism, typically they have left-sided disease with multiple complications, including aortic regurgitation and heart failure,” the cardiologist continued.

This description underscored one of Dr. O’Gara’s major points about the challenges posed by infective endocarditis in contemporary practice: “Expect the unexpected,” he advised. “When you’ve seen one case of infective endocarditis, you’ve seen one case of infective endocarditis.”
 

Outcomes are ‘sobering’

In the current era, outcomes are “sobering,” the cardiologist noted. Infective endocarditis carries a 6-month mortality rate of 20%-25% despite early surgery being performed during the index hospitalization in up to 60% of patients, with a relatively high perioperative mortality rate of about 10%. However, the risk of reinfection occurring in a newly implanted cardiac valve is impressively low at about 2%.

Refer early for multimodality imaging and surgical consultation

Transesophageal echocardiography is valuable in assessment of the infected valve. However, when extravalvular extension of the infection is suspected and the echo assessment is nondiagnostic or indeterminate, it’s time to quickly move on to advanced imaging, such as PET-CT.

The ACC/American Heart Association class I recommendations for early surgery in infected native valves haven’t changed substantially in over a decade. Based largely on observational data, there is an association between early surgery and lower in-hospital mortality (Lancet. 2012 Mar 10;379[9819]:965-975).

Class IIa recommendations for native valve surgery include recurrent emboli and a persistent vegetation despite appropriate antibiotic therapy. A “very controversial” class IIb recommendation for surgery because of weak supporting data is the identification of a mobile vegetation larger than 10 mm, particularly if it’s located on an anterior mitral valve leaflet, he said.

If the decision is made to forgo early surgery, be sure to repeat transesophageal echocardiography on day 7-10 to reassess the size of the patient’s vegetation.

“There is an association between size of vegetation and 1-year mortality, with a cut point of greater than 15 mm. Some would argue this constitutes a reasonable indication for early surgery,” Dr. O’Gara noted.

The embolization rate in patients with infective endocarditis is highest during the day before presentation, the day of presentation, and through the first 2 days afterward. The rate drops precipitously within 2 weeks after initiation of appropriate antibiotic therapy. Thus, to utilize early surgery to maximum effect in order to decrease the risk of embolization, it makes sense to operate within the first several days following presentation, before antibiotics have had sufficient time to catch up with the evolving disease process.
 

Don’t use half measures when it comes to removal of cardiac implanted electronic devices

The guidelines are clear regarding infected pacemakers, implanted cardioverter-defibrillators, and cardiac resynchronization devices: “It all needs to come out,” Dr. O’Gara emphasized. That includes all leads and the generator in patients with documented infection of only one portion of the device system, as a class I, level of evidence B recommendation. Moreover, complete removal of a pacemaker or defibrillator system is deemed “reasonable” as a class IIa recommendation in all patients with valvular infection caused by S. aureus or fungi even in the absence of evidence of device infection.

“I think we as general cardiologists have become increasingly impressed about how sick and festering these kinds of patients can become, even when we’re not able to prove that the lead is infected. The lead looks okay on transesophageal echo or PET-CT, blood cultures are negative, the valvular heart disease is really not that advanced, but several days go by and the patient is just not responding. We should have a high index of suspicion that there’s an infection we cannot appreciate. But obviously, you make these difficult decisions in consultation with your electrophysiology colleagues,” he added.
 

Know when the cardiologist should say ‘no’ to early aggressive surgery

While an aggressive early surgical approach often pays off in terms of prevention of embolic sequelae and a reduction in heart failure, the timing of surgery in the 20%-40% of patients with infective endocarditis who present with stroke or other neurologic complications remains controversial. An international group of Canadian and French cardiac surgeons and neurologists developed a useful algorithm regarding the types of neurologic complications for which early cardiac surgery is a poor idea because of the high risk of neurologic exacerbation. For example, a mycotic neuroaneurysm is grounds for postponement of cardiac surgery for at least 4 weeks (Circulation. 2016 Oct 25;134[17]:1280-92).

Dr. O’Gara reported receiving funding from the National Heart, Lung and Blood Institute, the National Institute of Dental and Craniofacial Research, from Medtronic in conjunction with the ongoing pivotal APOLLO transcatheter mitral valve replacement trial, and from Edwards Lifesciences for the ongoing EARLY TAVR trial.

[email protected]

SNOWMASS, COLO. – Infective endocarditis in 2019 is very different from the disease most physicians encountered in training, both in terms of epidemiology and clinical presentation, Patrick T. O’Gara, MD, observed at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

Bruce Jancin/MDedge News

The classic description of infective endocarditis provided by Sir William Osler, MD, was of a subacute bacterial infection characterized by a long latent phase of low-grade fever, back pain, weight loss, and night sweats. It was mainly a right-heart disease of younger individuals with an infected native valve, and the predominant pathogens were streptococci, Dr. O’Gara said.

“I think in the current era endocarditis is more often characterized by an acute illness with toxic features in the context of adults with a high burden of degenerative diseases – for example, patients with rheumatoid arthritis or psoriatic arthritis on immunosuppressive therapy, or diabetes, end-stage renal disease, and risk factors for hospital-acquired infection. Injectable drug use is through the roof, there’s a wider prevalence of cardiac implanted electronic devices, which are a wonderful place for bacteria to hide, and Staphylococcus aureus has certainly become the leading pathogen with regard to endocarditis in the United States, especially MRSA, often multidrug resistant,” said Dr. O’Gara, professor of medicine at Harvard Medical School, Boston.

“Also, no talk about endocarditis is sufficient without paying some attention to the opioid crisis in which we find ourselves. It’s one of the top three causes of death among young men in the United States, along with accidents and gun violence. No region of the country is spared. This has completely inundated our ER and hospitalist services and our inpatient cardiology services with folks who are often repeat offenders when it comes to the difficulty in being able to give up an injectable drug use habit. They have multiple infections and hospitalizations, tricuspid valve involvement, and depending upon the aggressiveness of the Staphylococcus organism, typically they have left-sided disease with multiple complications, including aortic regurgitation and heart failure,” the cardiologist continued.

This description underscored one of Dr. O’Gara’s major points about the challenges posed by infective endocarditis in contemporary practice: “Expect the unexpected,” he advised. “When you’ve seen one case of infective endocarditis, you’ve seen one case of infective endocarditis.”
 

Outcomes are ‘sobering’

In the current era, outcomes are “sobering,” the cardiologist noted. Infective endocarditis carries a 6-month mortality rate of 20%-25% despite early surgery being performed during the index hospitalization in up to 60% of patients, with a relatively high perioperative mortality rate of about 10%. However, the risk of reinfection occurring in a newly implanted cardiac valve is impressively low at about 2%.

Refer early for multimodality imaging and surgical consultation

Transesophageal echocardiography is valuable in assessment of the infected valve. However, when extravalvular extension of the infection is suspected and the echo assessment is nondiagnostic or indeterminate, it’s time to quickly move on to advanced imaging, such as PET-CT.

The ACC/American Heart Association class I recommendations for early surgery in infected native valves haven’t changed substantially in over a decade. Based largely on observational data, there is an association between early surgery and lower in-hospital mortality (Lancet. 2012 Mar 10;379[9819]:965-975).

Class IIa recommendations for native valve surgery include recurrent emboli and a persistent vegetation despite appropriate antibiotic therapy. A “very controversial” class IIb recommendation for surgery because of weak supporting data is the identification of a mobile vegetation larger than 10 mm, particularly if it’s located on an anterior mitral valve leaflet, he said.

If the decision is made to forgo early surgery, be sure to repeat transesophageal echocardiography on day 7-10 to reassess the size of the patient’s vegetation.

“There is an association between size of vegetation and 1-year mortality, with a cut point of greater than 15 mm. Some would argue this constitutes a reasonable indication for early surgery,” Dr. O’Gara noted.

The embolization rate in patients with infective endocarditis is highest during the day before presentation, the day of presentation, and through the first 2 days afterward. The rate drops precipitously within 2 weeks after initiation of appropriate antibiotic therapy. Thus, to utilize early surgery to maximum effect in order to decrease the risk of embolization, it makes sense to operate within the first several days following presentation, before antibiotics have had sufficient time to catch up with the evolving disease process.
 

Don’t use half measures when it comes to removal of cardiac implanted electronic devices

The guidelines are clear regarding infected pacemakers, implanted cardioverter-defibrillators, and cardiac resynchronization devices: “It all needs to come out,” Dr. O’Gara emphasized. That includes all leads and the generator in patients with documented infection of only one portion of the device system, as a class I, level of evidence B recommendation. Moreover, complete removal of a pacemaker or defibrillator system is deemed “reasonable” as a class IIa recommendation in all patients with valvular infection caused by S. aureus or fungi even in the absence of evidence of device infection.

“I think we as general cardiologists have become increasingly impressed about how sick and festering these kinds of patients can become, even when we’re not able to prove that the lead is infected. The lead looks okay on transesophageal echo or PET-CT, blood cultures are negative, the valvular heart disease is really not that advanced, but several days go by and the patient is just not responding. We should have a high index of suspicion that there’s an infection we cannot appreciate. But obviously, you make these difficult decisions in consultation with your electrophysiology colleagues,” he added.
 

Know when the cardiologist should say ‘no’ to early aggressive surgery

While an aggressive early surgical approach often pays off in terms of prevention of embolic sequelae and a reduction in heart failure, the timing of surgery in the 20%-40% of patients with infective endocarditis who present with stroke or other neurologic complications remains controversial. An international group of Canadian and French cardiac surgeons and neurologists developed a useful algorithm regarding the types of neurologic complications for which early cardiac surgery is a poor idea because of the high risk of neurologic exacerbation. For example, a mycotic neuroaneurysm is grounds for postponement of cardiac surgery for at least 4 weeks (Circulation. 2016 Oct 25;134[17]:1280-92).

Dr. O’Gara reported receiving funding from the National Heart, Lung and Blood Institute, the National Institute of Dental and Craniofacial Research, from Medtronic in conjunction with the ongoing pivotal APOLLO transcatheter mitral valve replacement trial, and from Edwards Lifesciences for the ongoing EARLY TAVR trial.

[email protected]

SNOWMASS, COLO. – Infective endocarditis in 2019 is very different from the disease most physicians encountered in training, both in terms of epidemiology and clinical presentation, Patrick T. O’Gara, MD, observed at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

Bruce Jancin/MDedge News

The classic description of infective endocarditis provided by Sir William Osler, MD, was of a subacute bacterial infection characterized by a long latent phase of low-grade fever, back pain, weight loss, and night sweats. It was mainly a right-heart disease of younger individuals with an infected native valve, and the predominant pathogens were streptococci, Dr. O’Gara said.

“I think in the current era endocarditis is more often characterized by an acute illness with toxic features in the context of adults with a high burden of degenerative diseases – for example, patients with rheumatoid arthritis or psoriatic arthritis on immunosuppressive therapy, or diabetes, end-stage renal disease, and risk factors for hospital-acquired infection. Injectable drug use is through the roof, there’s a wider prevalence of cardiac implanted electronic devices, which are a wonderful place for bacteria to hide, and Staphylococcus aureus has certainly become the leading pathogen with regard to endocarditis in the United States, especially MRSA, often multidrug resistant,” said Dr. O’Gara, professor of medicine at Harvard Medical School, Boston.

“Also, no talk about endocarditis is sufficient without paying some attention to the opioid crisis in which we find ourselves. It’s one of the top three causes of death among young men in the United States, along with accidents and gun violence. No region of the country is spared. This has completely inundated our ER and hospitalist services and our inpatient cardiology services with folks who are often repeat offenders when it comes to the difficulty in being able to give up an injectable drug use habit. They have multiple infections and hospitalizations, tricuspid valve involvement, and depending upon the aggressiveness of the Staphylococcus organism, typically they have left-sided disease with multiple complications, including aortic regurgitation and heart failure,” the cardiologist continued.

This description underscored one of Dr. O’Gara’s major points about the challenges posed by infective endocarditis in contemporary practice: “Expect the unexpected,” he advised. “When you’ve seen one case of infective endocarditis, you’ve seen one case of infective endocarditis.”
 

Outcomes are ‘sobering’

In the current era, outcomes are “sobering,” the cardiologist noted. Infective endocarditis carries a 6-month mortality rate of 20%-25% despite early surgery being performed during the index hospitalization in up to 60% of patients, with a relatively high perioperative mortality rate of about 10%. However, the risk of reinfection occurring in a newly implanted cardiac valve is impressively low at about 2%.

Refer early for multimodality imaging and surgical consultation

Transesophageal echocardiography is valuable in assessment of the infected valve. However, when extravalvular extension of the infection is suspected and the echo assessment is nondiagnostic or indeterminate, it’s time to quickly move on to advanced imaging, such as PET-CT.

The ACC/American Heart Association class I recommendations for early surgery in infected native valves haven’t changed substantially in over a decade. Based largely on observational data, there is an association between early surgery and lower in-hospital mortality (Lancet. 2012 Mar 10;379[9819]:965-975).

Class IIa recommendations for native valve surgery include recurrent emboli and a persistent vegetation despite appropriate antibiotic therapy. A “very controversial” class IIb recommendation for surgery because of weak supporting data is the identification of a mobile vegetation larger than 10 mm, particularly if it’s located on an anterior mitral valve leaflet, he said.

If the decision is made to forgo early surgery, be sure to repeat transesophageal echocardiography on day 7-10 to reassess the size of the patient’s vegetation.

“There is an association between size of vegetation and 1-year mortality, with a cut point of greater than 15 mm. Some would argue this constitutes a reasonable indication for early surgery,” Dr. O’Gara noted.

The embolization rate in patients with infective endocarditis is highest during the day before presentation, the day of presentation, and through the first 2 days afterward. The rate drops precipitously within 2 weeks after initiation of appropriate antibiotic therapy. Thus, to utilize early surgery to maximum effect in order to decrease the risk of embolization, it makes sense to operate within the first several days following presentation, before antibiotics have had sufficient time to catch up with the evolving disease process.
 

Don’t use half measures when it comes to removal of cardiac implanted electronic devices

The guidelines are clear regarding infected pacemakers, implanted cardioverter-defibrillators, and cardiac resynchronization devices: “It all needs to come out,” Dr. O’Gara emphasized. That includes all leads and the generator in patients with documented infection of only one portion of the device system, as a class I, level of evidence B recommendation. Moreover, complete removal of a pacemaker or defibrillator system is deemed “reasonable” as a class IIa recommendation in all patients with valvular infection caused by S. aureus or fungi even in the absence of evidence of device infection.

“I think we as general cardiologists have become increasingly impressed about how sick and festering these kinds of patients can become, even when we’re not able to prove that the lead is infected. The lead looks okay on transesophageal echo or PET-CT, blood cultures are negative, the valvular heart disease is really not that advanced, but several days go by and the patient is just not responding. We should have a high index of suspicion that there’s an infection we cannot appreciate. But obviously, you make these difficult decisions in consultation with your electrophysiology colleagues,” he added.
 

Know when the cardiologist should say ‘no’ to early aggressive surgery

While an aggressive early surgical approach often pays off in terms of prevention of embolic sequelae and a reduction in heart failure, the timing of surgery in the 20%-40% of patients with infective endocarditis who present with stroke or other neurologic complications remains controversial. An international group of Canadian and French cardiac surgeons and neurologists developed a useful algorithm regarding the types of neurologic complications for which early cardiac surgery is a poor idea because of the high risk of neurologic exacerbation. For example, a mycotic neuroaneurysm is grounds for postponement of cardiac surgery for at least 4 weeks (Circulation. 2016 Oct 25;134[17]:1280-92).

Dr. O’Gara reported receiving funding from the National Heart, Lung and Blood Institute, the National Institute of Dental and Craniofacial Research, from Medtronic in conjunction with the ongoing pivotal APOLLO transcatheter mitral valve replacement trial, and from Edwards Lifesciences for the ongoing EARLY TAVR trial.

[email protected]

Case Report

A 60-year-old Cambodian woman presented with recurrent fever (temperature, up to 38.8°C) 7 months after receiving a kidney transplant secondary to polycystic kidney disease. Fever was attributed to recurrent pyelonephritis of the native kidneys while on mycophenolate mofetil, tacrolimus, and prednisone. As a result, she underwent a bilateral native nephrectomy and was found to have peritoneal nodules. Pathology of both native kidneys and peritoneal tissue revealed caseating granulomas and acid-fast bacilli (AFB) diagnostic for kidney and peritoneal tuberculosis (TB). She had no history of TB, and a TB skin test (purified protein derivative [PPD]) upon entering the United States from Cambodia a decade earlier was negative. Additionally, her pretransplantation PPD was negative.

Treatment with isoniazid, ethambutol, pyrazinamide, and levofloxacin was initiated immediately upon diagnosis, and all of her immunosuppressive medications—mycophenolate mofetil, tacrolimus, and prednisone—were discontinued. Her symptoms subsided within 1 week, and she was discharged from the hospital. Over the next 2 months, her immunosuppressive medications were restarted, and her TB medications were periodically discontinued by the Tuberculosis Control Program at the Department of Health (Philadelphia, Pennsylvania) due to severe thrombocytopenia. During this time, she was closely monitored twice weekly in the clinic with blood draws performed weekly.

Approximately 10 weeks after initiation of treatment, she noted recurrent subjective fever (temperature, up to 38.8°C) and painful lesions on the right side of the flank, left breast, and left arm of 3 days’ duration. Physical examination revealed a warm, dull red, tender nodule on the right side of the flank (Figure 1) and subcutaneous nodules with no overlying skin changes on the left breast and left arm. A biopsy of the lesion on the right side of the flank was performed, which resulted in substantial purulent drainage. Histologic analysis showed an inflammatory infiltrate within the deep dermis composed of neutrophils, macrophages, and giant cells, indicative of suppurative granulomatous dermatitis (Figure 2). Ziehl-Neelsen stain demonstrated rare AFB within the cytoplasm of macrophages, suggestive of Mycobacterium tuberculosis infection (Figure 3). A repeat chest radiograph was normal.

Comment

Clinical Presentation
Cutaneous TB is an uncommon manifestation of TB that can occur either exogenously or endogenously.¹ It tends to occur primarily in previously infected TB patients through hematogenous, lymphatic, or contiguous spread.² Due to their immunocompromised state, solid organ transplant recipients have an increased incidence of primary and reactivated latent TB reported to be 20 to 74 times greater than the general population.^3,4 One report stated the total incidence of posttransplant TB as 0.48% in the West and 11.8% in endemic regions such as India.⁵ The occurrence of cutaneous TB is rare among solid organ transplant recipients.¹ On average, a diagnosis of latent TB is made 9 months after transplantation because of the opportunistic nature of M tuberculosis in an immunosuppressed environment.⁶

TB Subtypes
Cutaneous TB can be in the form of localized disease (eg, primary tuberculous chancre, TB verrucosa cutis, lupus vulgaris, smear-negative scrofuloderma), disseminated disease (eg, disseminated TB, TB gumma, orificial TB, miliary cutaneous TB), or tuberculids (eg, papulonecrotic tuberculid, lichen scrofulosorum, erythema induratum).⁷ Due to the pustular epithelioid cell granulomas and AFB positivity of the involved cutaneous lesions, our patient’s TB can be classified as a metastatic TB abscess or gummatous TB.⁷

Metastatic TB abscess, an uncommon subtype of cutaneous TB, generally is only seen in malnourished children and notably immunocompromised individuals.^2,8,9 In these individuals, systemic failure of cell-mediated immunity enables M tuberculosis to hematogenously infect various organs of the body, resulting in alternative forms of TB, such as gummatous-type TB.¹⁰ One study reported that of the 0.1% of dermatology patients presenting with cutaneous TB, only 5.4% of these individuals had the rarer gummatous form.⁷ These metastatic TB abscesses begin as a single or multiple nontender subcutaneous nodule(s), which breaks down and softens to form a draining sinus abscess.^2,8,9 Abscesses are most commonly seen on the trunk and extremities; however, they can be found nearly anywhere on the body.⁸ The pathology of cutaneous TB lesions demonstrates caseating necrosis with epithelioid and giant cells forming a surrounding rim.⁹

Diagnosis
Diagnosis may be difficult because of the vast number of dermatologic conditions that resemble cutaneous TB, including mycoses, sarcoidosis, leishmaniasis, leprosy, syphilis, other non-TB mycobacteria, and Wegener granulomatosis.⁹ Thus, confirmatory diagnosis is made via clinical presentation, detailed history and physical examination, and laboratory tests.¹¹ These tests include the Mantoux tuberculin skin test (PPD or TST) or IFN-γ release assays (QuantiFERON-TB Gold test), identification of AFB on skin biopsy, and isolation of M tuberculosis from tissue culture or polymerase chain reaction.¹¹Given our patient’s history, clinical presentation, and the identification of mycobacteria with AFB stain, the diagnosis of cutaneous gummatous TB was confirmed.

At-Risk Populations
The recommendation for the identification of at-risk populations for latent TB testing and treatment have been clearly defined by the World Health Organization (Table).¹² Our patient met 2 of these criteria: she had been preparing for organ transplantation and was from a country with high TB burden. Such at-risk patients should be tested for a latent TB infection with either IFN-γ release assays or PPD.¹²These recommendations are supported by the American Thoracic Society, which specifies that a positive PPD test in a solid organ transplant recipient is defined as having induration greater than 5 mm.¹³ However, even with a high index of suspicion, it has been reported that as many as 75% to 80% of organ recipients who developed TB had a false-negative pretransplantation PPD due to anergy from immunosuppression.¹⁴ Given the notable risk for TB in organ transplant recipients on immunosuppressive medications, these patients should receive screening tests with high sensitivity and specificity, while controlling for possible anergy. Unfortunately, the role of anergy testing in the diagnosis of latent TB is not well defined, and thus not recommended at this time.^13,15 It is recommended to repeat PPD testing 7 to 10 days after the first test as a booster effect to rule out false-negative results.¹⁵

Finally, thrombocytopenia is an infrequent, life-threatening complication that can be acquired by immunocompromised patients on anti-TB therapy.¹⁷ Drug-induced thrombocytopenia can be caused by a variety of medications, including rifampicin, isoniazid, ethambutol, and pyrazinamide. Diagnosis of drug-induced thrombocytopenia can be confirmed only after discontinuation of the suspected drug and subsequent resolution of the thrombocytopenia.¹⁷ Our patient initially became thrombocytopenic while taking isoniazid, ethambutol, pyrazinamide, and levofloxacin. However, her platelet levels improved once the pyrazinamide was discontinued, thereby suggesting pyrazinamide-induced thrombocytopenia.

Conclusion

The risk for infectious disease reactivation in an immunocompromised patient undergoing transplant surgery is notable. Our findings emphasize the value of a comprehensive pretransplant evaluation, vigilance even when test results appear negative, and treatment of latent TB within this population.^16,18,19 Furthermore, this case illustrates a noteworthy example of a rare form of cutaneous TB, which should be considered and included in the differential for cutaneous lesions in an immunosuppressed patient.

Case Report

A 60-year-old Cambodian woman presented with recurrent fever (temperature, up to 38.8°C) 7 months after receiving a kidney transplant secondary to polycystic kidney disease. Fever was attributed to recurrent pyelonephritis of the native kidneys while on mycophenolate mofetil, tacrolimus, and prednisone. As a result, she underwent a bilateral native nephrectomy and was found to have peritoneal nodules. Pathology of both native kidneys and peritoneal tissue revealed caseating granulomas and acid-fast bacilli (AFB) diagnostic for kidney and peritoneal tuberculosis (TB). She had no history of TB, and a TB skin test (purified protein derivative [PPD]) upon entering the United States from Cambodia a decade earlier was negative. Additionally, her pretransplantation PPD was negative.

Treatment with isoniazid, ethambutol, pyrazinamide, and levofloxacin was initiated immediately upon diagnosis, and all of her immunosuppressive medications—mycophenolate mofetil, tacrolimus, and prednisone—were discontinued. Her symptoms subsided within 1 week, and she was discharged from the hospital. Over the next 2 months, her immunosuppressive medications were restarted, and her TB medications were periodically discontinued by the Tuberculosis Control Program at the Department of Health (Philadelphia, Pennsylvania) due to severe thrombocytopenia. During this time, she was closely monitored twice weekly in the clinic with blood draws performed weekly.

Approximately 10 weeks after initiation of treatment, she noted recurrent subjective fever (temperature, up to 38.8°C) and painful lesions on the right side of the flank, left breast, and left arm of 3 days’ duration. Physical examination revealed a warm, dull red, tender nodule on the right side of the flank (Figure 1) and subcutaneous nodules with no overlying skin changes on the left breast and left arm. A biopsy of the lesion on the right side of the flank was performed, which resulted in substantial purulent drainage. Histologic analysis showed an inflammatory infiltrate within the deep dermis composed of neutrophils, macrophages, and giant cells, indicative of suppurative granulomatous dermatitis (Figure 2). Ziehl-Neelsen stain demonstrated rare AFB within the cytoplasm of macrophages, suggestive of Mycobacterium tuberculosis infection (Figure 3). A repeat chest radiograph was normal.

Comment

Clinical Presentation
Cutaneous TB is an uncommon manifestation of TB that can occur either exogenously or endogenously.¹ It tends to occur primarily in previously infected TB patients through hematogenous, lymphatic, or contiguous spread.² Due to their immunocompromised state, solid organ transplant recipients have an increased incidence of primary and reactivated latent TB reported to be 20 to 74 times greater than the general population.^3,4 One report stated the total incidence of posttransplant TB as 0.48% in the West and 11.8% in endemic regions such as India.⁵ The occurrence of cutaneous TB is rare among solid organ transplant recipients.¹ On average, a diagnosis of latent TB is made 9 months after transplantation because of the opportunistic nature of M tuberculosis in an immunosuppressed environment.⁶

TB Subtypes
Cutaneous TB can be in the form of localized disease (eg, primary tuberculous chancre, TB verrucosa cutis, lupus vulgaris, smear-negative scrofuloderma), disseminated disease (eg, disseminated TB, TB gumma, orificial TB, miliary cutaneous TB), or tuberculids (eg, papulonecrotic tuberculid, lichen scrofulosorum, erythema induratum).⁷ Due to the pustular epithelioid cell granulomas and AFB positivity of the involved cutaneous lesions, our patient’s TB can be classified as a metastatic TB abscess or gummatous TB.⁷

Metastatic TB abscess, an uncommon subtype of cutaneous TB, generally is only seen in malnourished children and notably immunocompromised individuals.^2,8,9 In these individuals, systemic failure of cell-mediated immunity enables M tuberculosis to hematogenously infect various organs of the body, resulting in alternative forms of TB, such as gummatous-type TB.¹⁰ One study reported that of the 0.1% of dermatology patients presenting with cutaneous TB, only 5.4% of these individuals had the rarer gummatous form.⁷ These metastatic TB abscesses begin as a single or multiple nontender subcutaneous nodule(s), which breaks down and softens to form a draining sinus abscess.^2,8,9 Abscesses are most commonly seen on the trunk and extremities; however, they can be found nearly anywhere on the body.⁸ The pathology of cutaneous TB lesions demonstrates caseating necrosis with epithelioid and giant cells forming a surrounding rim.⁹

Diagnosis
Diagnosis may be difficult because of the vast number of dermatologic conditions that resemble cutaneous TB, including mycoses, sarcoidosis, leishmaniasis, leprosy, syphilis, other non-TB mycobacteria, and Wegener granulomatosis.⁹ Thus, confirmatory diagnosis is made via clinical presentation, detailed history and physical examination, and laboratory tests.¹¹ These tests include the Mantoux tuberculin skin test (PPD or TST) or IFN-γ release assays (QuantiFERON-TB Gold test), identification of AFB on skin biopsy, and isolation of M tuberculosis from tissue culture or polymerase chain reaction.¹¹Given our patient’s history, clinical presentation, and the identification of mycobacteria with AFB stain, the diagnosis of cutaneous gummatous TB was confirmed.

At-Risk Populations
The recommendation for the identification of at-risk populations for latent TB testing and treatment have been clearly defined by the World Health Organization (Table).¹² Our patient met 2 of these criteria: she had been preparing for organ transplantation and was from a country with high TB burden. Such at-risk patients should be tested for a latent TB infection with either IFN-γ release assays or PPD.¹²These recommendations are supported by the American Thoracic Society, which specifies that a positive PPD test in a solid organ transplant recipient is defined as having induration greater than 5 mm.¹³ However, even with a high index of suspicion, it has been reported that as many as 75% to 80% of organ recipients who developed TB had a false-negative pretransplantation PPD due to anergy from immunosuppression.¹⁴ Given the notable risk for TB in organ transplant recipients on immunosuppressive medications, these patients should receive screening tests with high sensitivity and specificity, while controlling for possible anergy. Unfortunately, the role of anergy testing in the diagnosis of latent TB is not well defined, and thus not recommended at this time.^13,15 It is recommended to repeat PPD testing 7 to 10 days after the first test as a booster effect to rule out false-negative results.¹⁵

Finally, thrombocytopenia is an infrequent, life-threatening complication that can be acquired by immunocompromised patients on anti-TB therapy.¹⁷ Drug-induced thrombocytopenia can be caused by a variety of medications, including rifampicin, isoniazid, ethambutol, and pyrazinamide. Diagnosis of drug-induced thrombocytopenia can be confirmed only after discontinuation of the suspected drug and subsequent resolution of the thrombocytopenia.¹⁷ Our patient initially became thrombocytopenic while taking isoniazid, ethambutol, pyrazinamide, and levofloxacin. However, her platelet levels improved once the pyrazinamide was discontinued, thereby suggesting pyrazinamide-induced thrombocytopenia.

Conclusion

The risk for infectious disease reactivation in an immunocompromised patient undergoing transplant surgery is notable. Our findings emphasize the value of a comprehensive pretransplant evaluation, vigilance even when test results appear negative, and treatment of latent TB within this population.^16,18,19 Furthermore, this case illustrates a noteworthy example of a rare form of cutaneous TB, which should be considered and included in the differential for cutaneous lesions in an immunosuppressed patient.

Case Report

A 60-year-old Cambodian woman presented with recurrent fever (temperature, up to 38.8°C) 7 months after receiving a kidney transplant secondary to polycystic kidney disease. Fever was attributed to recurrent pyelonephritis of the native kidneys while on mycophenolate mofetil, tacrolimus, and prednisone. As a result, she underwent a bilateral native nephrectomy and was found to have peritoneal nodules. Pathology of both native kidneys and peritoneal tissue revealed caseating granulomas and acid-fast bacilli (AFB) diagnostic for kidney and peritoneal tuberculosis (TB). She had no history of TB, and a TB skin test (purified protein derivative [PPD]) upon entering the United States from Cambodia a decade earlier was negative. Additionally, her pretransplantation PPD was negative.

Treatment with isoniazid, ethambutol, pyrazinamide, and levofloxacin was initiated immediately upon diagnosis, and all of her immunosuppressive medications—mycophenolate mofetil, tacrolimus, and prednisone—were discontinued. Her symptoms subsided within 1 week, and she was discharged from the hospital. Over the next 2 months, her immunosuppressive medications were restarted, and her TB medications were periodically discontinued by the Tuberculosis Control Program at the Department of Health (Philadelphia, Pennsylvania) due to severe thrombocytopenia. During this time, she was closely monitored twice weekly in the clinic with blood draws performed weekly.

Approximately 10 weeks after initiation of treatment, she noted recurrent subjective fever (temperature, up to 38.8°C) and painful lesions on the right side of the flank, left breast, and left arm of 3 days’ duration. Physical examination revealed a warm, dull red, tender nodule on the right side of the flank (Figure 1) and subcutaneous nodules with no overlying skin changes on the left breast and left arm. A biopsy of the lesion on the right side of the flank was performed, which resulted in substantial purulent drainage. Histologic analysis showed an inflammatory infiltrate within the deep dermis composed of neutrophils, macrophages, and giant cells, indicative of suppurative granulomatous dermatitis (Figure 2). Ziehl-Neelsen stain demonstrated rare AFB within the cytoplasm of macrophages, suggestive of Mycobacterium tuberculosis infection (Figure 3). A repeat chest radiograph was normal.

Comment

Clinical Presentation
Cutaneous TB is an uncommon manifestation of TB that can occur either exogenously or endogenously.¹ It tends to occur primarily in previously infected TB patients through hematogenous, lymphatic, or contiguous spread.² Due to their immunocompromised state, solid organ transplant recipients have an increased incidence of primary and reactivated latent TB reported to be 20 to 74 times greater than the general population.^3,4 One report stated the total incidence of posttransplant TB as 0.48% in the West and 11.8% in endemic regions such as India.⁵ The occurrence of cutaneous TB is rare among solid organ transplant recipients.¹ On average, a diagnosis of latent TB is made 9 months after transplantation because of the opportunistic nature of M tuberculosis in an immunosuppressed environment.⁶

TB Subtypes
Cutaneous TB can be in the form of localized disease (eg, primary tuberculous chancre, TB verrucosa cutis, lupus vulgaris, smear-negative scrofuloderma), disseminated disease (eg, disseminated TB, TB gumma, orificial TB, miliary cutaneous TB), or tuberculids (eg, papulonecrotic tuberculid, lichen scrofulosorum, erythema induratum).⁷ Due to the pustular epithelioid cell granulomas and AFB positivity of the involved cutaneous lesions, our patient’s TB can be classified as a metastatic TB abscess or gummatous TB.⁷

Metastatic TB abscess, an uncommon subtype of cutaneous TB, generally is only seen in malnourished children and notably immunocompromised individuals.^2,8,9 In these individuals, systemic failure of cell-mediated immunity enables M tuberculosis to hematogenously infect various organs of the body, resulting in alternative forms of TB, such as gummatous-type TB.¹⁰ One study reported that of the 0.1% of dermatology patients presenting with cutaneous TB, only 5.4% of these individuals had the rarer gummatous form.⁷ These metastatic TB abscesses begin as a single or multiple nontender subcutaneous nodule(s), which breaks down and softens to form a draining sinus abscess.^2,8,9 Abscesses are most commonly seen on the trunk and extremities; however, they can be found nearly anywhere on the body.⁸ The pathology of cutaneous TB lesions demonstrates caseating necrosis with epithelioid and giant cells forming a surrounding rim.⁹

Diagnosis
Diagnosis may be difficult because of the vast number of dermatologic conditions that resemble cutaneous TB, including mycoses, sarcoidosis, leishmaniasis, leprosy, syphilis, other non-TB mycobacteria, and Wegener granulomatosis.⁹ Thus, confirmatory diagnosis is made via clinical presentation, detailed history and physical examination, and laboratory tests.¹¹ These tests include the Mantoux tuberculin skin test (PPD or TST) or IFN-γ release assays (QuantiFERON-TB Gold test), identification of AFB on skin biopsy, and isolation of M tuberculosis from tissue culture or polymerase chain reaction.¹¹Given our patient’s history, clinical presentation, and the identification of mycobacteria with AFB stain, the diagnosis of cutaneous gummatous TB was confirmed.

At-Risk Populations
The recommendation for the identification of at-risk populations for latent TB testing and treatment have been clearly defined by the World Health Organization (Table).¹² Our patient met 2 of these criteria: she had been preparing for organ transplantation and was from a country with high TB burden. Such at-risk patients should be tested for a latent TB infection with either IFN-γ release assays or PPD.¹²These recommendations are supported by the American Thoracic Society, which specifies that a positive PPD test in a solid organ transplant recipient is defined as having induration greater than 5 mm.¹³ However, even with a high index of suspicion, it has been reported that as many as 75% to 80% of organ recipients who developed TB had a false-negative pretransplantation PPD due to anergy from immunosuppression.¹⁴ Given the notable risk for TB in organ transplant recipients on immunosuppressive medications, these patients should receive screening tests with high sensitivity and specificity, while controlling for possible anergy. Unfortunately, the role of anergy testing in the diagnosis of latent TB is not well defined, and thus not recommended at this time.^13,15 It is recommended to repeat PPD testing 7 to 10 days after the first test as a booster effect to rule out false-negative results.¹⁵

Finally, thrombocytopenia is an infrequent, life-threatening complication that can be acquired by immunocompromised patients on anti-TB therapy.¹⁷ Drug-induced thrombocytopenia can be caused by a variety of medications, including rifampicin, isoniazid, ethambutol, and pyrazinamide. Diagnosis of drug-induced thrombocytopenia can be confirmed only after discontinuation of the suspected drug and subsequent resolution of the thrombocytopenia.¹⁷ Our patient initially became thrombocytopenic while taking isoniazid, ethambutol, pyrazinamide, and levofloxacin. However, her platelet levels improved once the pyrazinamide was discontinued, thereby suggesting pyrazinamide-induced thrombocytopenia.

Conclusion

The risk for infectious disease reactivation in an immunocompromised patient undergoing transplant surgery is notable. Our findings emphasize the value of a comprehensive pretransplant evaluation, vigilance even when test results appear negative, and treatment of latent TB within this population.^16,18,19 Furthermore, this case illustrates a noteworthy example of a rare form of cutaneous TB, which should be considered and included in the differential for cutaneous lesions in an immunosuppressed patient.

Sarcoidosis is a systemic noncaseating granuloma­tous disease of unknown etiology. The skin is the second most common location for disease mani­festation following the lungs.¹ Cutaneous sarcoidosis is present in 35% of patients with sarcoidosis and may be further subtyped by its morphologic characteristics (eg, hyperpigmented, papular, nodular, atrophic, ulcer­ative, psoriasiform). Cutaneous sarcoidosis has an increased tendency to occur at areas of prior injury such as surgeries or tattoos.² Although sarcoidosis affects all races and sexes, it is more prevalent in women and in the black population.³ 

The clinical presentation of sarcoidosis is difficult due to its morphologic variation, allowing for a wide differential diagnosis. With our patient’s presentation of atrophic plaques, the differential diagnosis included granuloma annulare, necrobiosis lipoidica, tumid lupus erythematosus, leprosy, and sarcoidosis; however, biopsy is required for definitive diagnosis. The characteristic histopathology for cutaneous sarcoidosis includes nonca­seating granulomas (Figure, A) composed of epithelioid histiocytes with giant cells surrounded by a lympho­cytic infiltrate. Noncaseating granulomas are consid­ered specific to sarcoidosis and are present in 71% to 89% of biopsied lesions.⁴ Interestingly, our patient pre­sented with a rare subtype of atrophic ulcerative cutane­ous sarcoidosis, necrobiosis lipoidica–like sarcoidosis, which is more common in females and in the black population. It is characterized by pink to violaceous plaques with depressed centers and prominent necrotiz­ing granuloma (Figure, B) on histopathology. In a small case series, all 3 patients with necrobiosis lipoidica–like sarcoidosis were female and had systemic involvement at the time of diagnosis.⁵ 

Sarcoidosis typically is a systemic disease with only a limited number of cases presenting with isolated cutane­ous findings. Therefore, patients require a systemic evalu­ation, which may include a chest radiograph, complete blood cell count, ophthalmologic examinations, thyroid testing, and vitamin D monitoring, as well as an echocar­diogram and electrocardiogram.² 

Treatment is guided by the severity of disease. For isolated cutaneous lesions, topical or intralesional high-potency steroids have been shown to be effective.^6,7 Several studies also have shown phototherapy and laser therapy as well as surgical excision to be beneficial.^8-10 Once cutaneous lesions become disfiguring or systemic involvement is found, systemic corticosteroids or other immunomodulatory medications may be warranted.¹¹ Our patient was started on intralesional and topical high-potency steroids, which failed, and she was transitioned to methotrexate and adalimumab. Unfortunately, even with advanced therapies, our patient did not have notableresolution of the lesions.

Sarcoidosis is a systemic noncaseating granuloma­tous disease of unknown etiology. The skin is the second most common location for disease mani­festation following the lungs.¹ Cutaneous sarcoidosis is present in 35% of patients with sarcoidosis and may be further subtyped by its morphologic characteristics (eg, hyperpigmented, papular, nodular, atrophic, ulcer­ative, psoriasiform). Cutaneous sarcoidosis has an increased tendency to occur at areas of prior injury such as surgeries or tattoos.² Although sarcoidosis affects all races and sexes, it is more prevalent in women and in the black population.³ 

The clinical presentation of sarcoidosis is difficult due to its morphologic variation, allowing for a wide differential diagnosis. With our patient’s presentation of atrophic plaques, the differential diagnosis included granuloma annulare, necrobiosis lipoidica, tumid lupus erythematosus, leprosy, and sarcoidosis; however, biopsy is required for definitive diagnosis. The characteristic histopathology for cutaneous sarcoidosis includes nonca­seating granulomas (Figure, A) composed of epithelioid histiocytes with giant cells surrounded by a lympho­cytic infiltrate. Noncaseating granulomas are consid­ered specific to sarcoidosis and are present in 71% to 89% of biopsied lesions.⁴ Interestingly, our patient pre­sented with a rare subtype of atrophic ulcerative cutane­ous sarcoidosis, necrobiosis lipoidica–like sarcoidosis, which is more common in females and in the black population. It is characterized by pink to violaceous plaques with depressed centers and prominent necrotiz­ing granuloma (Figure, B) on histopathology. In a small case series, all 3 patients with necrobiosis lipoidica–like sarcoidosis were female and had systemic involvement at the time of diagnosis.⁵ 

Sarcoidosis typically is a systemic disease with only a limited number of cases presenting with isolated cutane­ous findings. Therefore, patients require a systemic evalu­ation, which may include a chest radiograph, complete blood cell count, ophthalmologic examinations, thyroid testing, and vitamin D monitoring, as well as an echocar­diogram and electrocardiogram.² 

Treatment is guided by the severity of disease. For isolated cutaneous lesions, topical or intralesional high-potency steroids have been shown to be effective.^6,7 Several studies also have shown phototherapy and laser therapy as well as surgical excision to be beneficial.^8-10 Once cutaneous lesions become disfiguring or systemic involvement is found, systemic corticosteroids or other immunomodulatory medications may be warranted.¹¹ Our patient was started on intralesional and topical high-potency steroids, which failed, and she was transitioned to methotrexate and adalimumab. Unfortunately, even with advanced therapies, our patient did not have notableresolution of the lesions.

Sarcoidosis is a systemic noncaseating granuloma­tous disease of unknown etiology. The skin is the second most common location for disease mani­festation following the lungs.¹ Cutaneous sarcoidosis is present in 35% of patients with sarcoidosis and may be further subtyped by its morphologic characteristics (eg, hyperpigmented, papular, nodular, atrophic, ulcer­ative, psoriasiform). Cutaneous sarcoidosis has an increased tendency to occur at areas of prior injury such as surgeries or tattoos.² Although sarcoidosis affects all races and sexes, it is more prevalent in women and in the black population.³ 

The clinical presentation of sarcoidosis is difficult due to its morphologic variation, allowing for a wide differential diagnosis. With our patient’s presentation of atrophic plaques, the differential diagnosis included granuloma annulare, necrobiosis lipoidica, tumid lupus erythematosus, leprosy, and sarcoidosis; however, biopsy is required for definitive diagnosis. The characteristic histopathology for cutaneous sarcoidosis includes nonca­seating granulomas (Figure, A) composed of epithelioid histiocytes with giant cells surrounded by a lympho­cytic infiltrate. Noncaseating granulomas are consid­ered specific to sarcoidosis and are present in 71% to 89% of biopsied lesions.⁴ Interestingly, our patient pre­sented with a rare subtype of atrophic ulcerative cutane­ous sarcoidosis, necrobiosis lipoidica–like sarcoidosis, which is more common in females and in the black population. It is characterized by pink to violaceous plaques with depressed centers and prominent necrotiz­ing granuloma (Figure, B) on histopathology. In a small case series, all 3 patients with necrobiosis lipoidica–like sarcoidosis were female and had systemic involvement at the time of diagnosis.⁵ 

Sarcoidosis typically is a systemic disease with only a limited number of cases presenting with isolated cutane­ous findings. Therefore, patients require a systemic evalu­ation, which may include a chest radiograph, complete blood cell count, ophthalmologic examinations, thyroid testing, and vitamin D monitoring, as well as an echocar­diogram and electrocardiogram.² 

Treatment is guided by the severity of disease. For isolated cutaneous lesions, topical or intralesional high-potency steroids have been shown to be effective.^6,7 Several studies also have shown phototherapy and laser therapy as well as surgical excision to be beneficial.^8-10 Once cutaneous lesions become disfiguring or systemic involvement is found, systemic corticosteroids or other immunomodulatory medications may be warranted.¹¹ Our patient was started on intralesional and topical high-potency steroids, which failed, and she was transitioned to methotrexate and adalimumab. Unfortunately, even with advanced therapies, our patient did not have notableresolution of the lesions.

The development of a prophylactic hepatitis C vaccine faces significant challenges, according to a Justin R. Bailey, MD, of Johns Hopkins University, Baltimore, and his colleagues.

luiscar/Thinkstock

Barriers to developing a prophylactic HCV vaccine include the great diversity of the virus, the limited models that are available for vaccine testing, and the currently incomplete understanding of protective immune responses, according to their review published in Gastroenterology.

Functionally, the inability to culture HCV, until recently, and continuing limitations of HCV culture systems pose challenges to standard production of a live-attenuated or inactivated whole HCV vaccine. In addition, there is the risk of causing HCV infection with live-attenuated vaccines.

On a practical level for all forms of vaccine development, a principal challenge “is the extraordinary genetic diversity of the virus. With 7 known genotypes and more than 80 subtypes, the genetic diversity of HCV exceeds that of human immunodeficiency virus-1,” according to the authors (Gastroenterology 2019;156[2]:418-30).

With regard to vaccine testing, there are also significant difficulties: There is a lack of in vitro systems and immunocompetent small-animal models useful for determining whether vaccination induces protective immunity. Although a use of an HCV-like virus, the rat Hepacivirus, provides a new small-animal model for vaccine testing, this virus has limited sequence analogy to HCV.

The development of immunity to HCV in humans is complex and under broad investigation. However, decades of research have revealed that HCV-specific CD4+ helper T cells, CD8+ cytotoxic T cells, and antibodies all play a role in protection against persistent HCV infection, according to the authors, and vaccine strategies to induce all three adaptive immune responses are in development.

“A prophylactic HCV vaccine is an important part of a successful strategy for global control. Although development is not easy, the quest is a worthy challenge,” the authors concluded.

Dr. Bailey and his colleagues reported that they had no conflicts.

[email protected]

SOURCE: Bailey JR et al. Gastroenterology 2019(2);156:418-30.

The development of a prophylactic hepatitis C vaccine faces significant challenges, according to a Justin R. Bailey, MD, of Johns Hopkins University, Baltimore, and his colleagues.

luiscar/Thinkstock

Barriers to developing a prophylactic HCV vaccine include the great diversity of the virus, the limited models that are available for vaccine testing, and the currently incomplete understanding of protective immune responses, according to their review published in Gastroenterology.

Functionally, the inability to culture HCV, until recently, and continuing limitations of HCV culture systems pose challenges to standard production of a live-attenuated or inactivated whole HCV vaccine. In addition, there is the risk of causing HCV infection with live-attenuated vaccines.

On a practical level for all forms of vaccine development, a principal challenge “is the extraordinary genetic diversity of the virus. With 7 known genotypes and more than 80 subtypes, the genetic diversity of HCV exceeds that of human immunodeficiency virus-1,” according to the authors (Gastroenterology 2019;156[2]:418-30).

With regard to vaccine testing, there are also significant difficulties: There is a lack of in vitro systems and immunocompetent small-animal models useful for determining whether vaccination induces protective immunity. Although a use of an HCV-like virus, the rat Hepacivirus, provides a new small-animal model for vaccine testing, this virus has limited sequence analogy to HCV.

The development of immunity to HCV in humans is complex and under broad investigation. However, decades of research have revealed that HCV-specific CD4+ helper T cells, CD8+ cytotoxic T cells, and antibodies all play a role in protection against persistent HCV infection, according to the authors, and vaccine strategies to induce all three adaptive immune responses are in development.

“A prophylactic HCV vaccine is an important part of a successful strategy for global control. Although development is not easy, the quest is a worthy challenge,” the authors concluded.

Dr. Bailey and his colleagues reported that they had no conflicts.

[email protected]

SOURCE: Bailey JR et al. Gastroenterology 2019(2);156:418-30.

The development of a prophylactic hepatitis C vaccine faces significant challenges, according to a Justin R. Bailey, MD, of Johns Hopkins University, Baltimore, and his colleagues.

luiscar/Thinkstock

Barriers to developing a prophylactic HCV vaccine include the great diversity of the virus, the limited models that are available for vaccine testing, and the currently incomplete understanding of protective immune responses, according to their review published in Gastroenterology.

Functionally, the inability to culture HCV, until recently, and continuing limitations of HCV culture systems pose challenges to standard production of a live-attenuated or inactivated whole HCV vaccine. In addition, there is the risk of causing HCV infection with live-attenuated vaccines.

On a practical level for all forms of vaccine development, a principal challenge “is the extraordinary genetic diversity of the virus. With 7 known genotypes and more than 80 subtypes, the genetic diversity of HCV exceeds that of human immunodeficiency virus-1,” according to the authors (Gastroenterology 2019;156[2]:418-30).

With regard to vaccine testing, there are also significant difficulties: There is a lack of in vitro systems and immunocompetent small-animal models useful for determining whether vaccination induces protective immunity. Although a use of an HCV-like virus, the rat Hepacivirus, provides a new small-animal model for vaccine testing, this virus has limited sequence analogy to HCV.

The development of immunity to HCV in humans is complex and under broad investigation. However, decades of research have revealed that HCV-specific CD4+ helper T cells, CD8+ cytotoxic T cells, and antibodies all play a role in protection against persistent HCV infection, according to the authors, and vaccine strategies to induce all three adaptive immune responses are in development.

“A prophylactic HCV vaccine is an important part of a successful strategy for global control. Although development is not easy, the quest is a worthy challenge,” the authors concluded.

Dr. Bailey and his colleagues reported that they had no conflicts.

[email protected]

SOURCE: Bailey JR et al. Gastroenterology 2019(2);156:418-30.

Mannose-binding lectin (MBL) and ficolin-2 appeared to be potential biomarkers for the development of hepatocellular carcinoma (HCC) in chronic hepatitis C virus (HCV) infection, according to the results of a biochemical analysis of human blood samples performed by PhD student Paywast J. Jalal of the University of Sulaimani (Iraq) and colleagues.

pixologicstudio/Thinkstock

Archived HCV-positive serum samples, including those from 31 patients who had developed HCC, were retrieved from the Trent HCV clinical cohort. They were compared with each other over time and against samples from HCV-infected individuals in the cohort who did not develop HCC. In addition, HCV-negative serum samples were obtained commercially and assessed identically. Circulating liver-expressed lectins, ficolin-2, ficolin-3, and MBL were all examined as potential biomarkers for the development of HCC, the authors wrote in Virology.

Binding of ficolin-3 to reference ligands was greater in chronic HCV infection, while ficolin-2 and MBL were significantly elevated in individuals who develop HCC, compared with HCV-infected individuals without HCC. Ficolin-2 and MBL were found to be elevated at 1 and 3 years prior to HCC diagnosis, respectively, suggesting they could be used as prognostic serum markers for the development of HCC.

“The strong evidence for an association between elevated MBL binding activity and the development of HCC is supportive for a larger prospective study of these biomarkers in HCV-induced liver cancer,” the researchers concluded.

This study was funded by a split-site PhD scholarship between the University of Sulaimani and the University of Nottingham (England). The authors reported they had no conflicts.

[email protected]

SOURCE: Jalal PJ et al. Virology. 2019;530:99-106.

Mannose-binding lectin (MBL) and ficolin-2 appeared to be potential biomarkers for the development of hepatocellular carcinoma (HCC) in chronic hepatitis C virus (HCV) infection, according to the results of a biochemical analysis of human blood samples performed by PhD student Paywast J. Jalal of the University of Sulaimani (Iraq) and colleagues.

pixologicstudio/Thinkstock

Archived HCV-positive serum samples, including those from 31 patients who had developed HCC, were retrieved from the Trent HCV clinical cohort. They were compared with each other over time and against samples from HCV-infected individuals in the cohort who did not develop HCC. In addition, HCV-negative serum samples were obtained commercially and assessed identically. Circulating liver-expressed lectins, ficolin-2, ficolin-3, and MBL were all examined as potential biomarkers for the development of HCC, the authors wrote in Virology.

Binding of ficolin-3 to reference ligands was greater in chronic HCV infection, while ficolin-2 and MBL were significantly elevated in individuals who develop HCC, compared with HCV-infected individuals without HCC. Ficolin-2 and MBL were found to be elevated at 1 and 3 years prior to HCC diagnosis, respectively, suggesting they could be used as prognostic serum markers for the development of HCC.

“The strong evidence for an association between elevated MBL binding activity and the development of HCC is supportive for a larger prospective study of these biomarkers in HCV-induced liver cancer,” the researchers concluded.

This study was funded by a split-site PhD scholarship between the University of Sulaimani and the University of Nottingham (England). The authors reported they had no conflicts.

[email protected]

SOURCE: Jalal PJ et al. Virology. 2019;530:99-106.

Mannose-binding lectin (MBL) and ficolin-2 appeared to be potential biomarkers for the development of hepatocellular carcinoma (HCC) in chronic hepatitis C virus (HCV) infection, according to the results of a biochemical analysis of human blood samples performed by PhD student Paywast J. Jalal of the University of Sulaimani (Iraq) and colleagues.

pixologicstudio/Thinkstock

Archived HCV-positive serum samples, including those from 31 patients who had developed HCC, were retrieved from the Trent HCV clinical cohort. They were compared with each other over time and against samples from HCV-infected individuals in the cohort who did not develop HCC. In addition, HCV-negative serum samples were obtained commercially and assessed identically. Circulating liver-expressed lectins, ficolin-2, ficolin-3, and MBL were all examined as potential biomarkers for the development of HCC, the authors wrote in Virology.

Binding of ficolin-3 to reference ligands was greater in chronic HCV infection, while ficolin-2 and MBL were significantly elevated in individuals who develop HCC, compared with HCV-infected individuals without HCC. Ficolin-2 and MBL were found to be elevated at 1 and 3 years prior to HCC diagnosis, respectively, suggesting they could be used as prognostic serum markers for the development of HCC.

“The strong evidence for an association between elevated MBL binding activity and the development of HCC is supportive for a larger prospective study of these biomarkers in HCV-induced liver cancer,” the researchers concluded.

This study was funded by a split-site PhD scholarship between the University of Sulaimani and the University of Nottingham (England). The authors reported they had no conflicts.

[email protected]

SOURCE: Jalal PJ et al. Virology. 2019;530:99-106.

Serious infections from Staphylococcus aureus caused nearly 20,000 deaths and 119,000 illnesses in the United States in 2017, according to data from a Vital Signs report issued by the Centers for Disease Control and Prevention. The data include both methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA).

Although MRSA infections in health care settings declined by approximately 17% during 2005-2012, rates plateaued during 2012-2017, Anne Schuchat, MD, principal deputy director of the CDC, said in a teleconference March 5 to present the findings. The report emphasizes the potential for serious illness and death with any staph infection and the need for ongoing vigilance on the part of clinicians, she said.

In addition, community-onset MSSA infections increased by 3.9%/year during 2012-2017. Data from previous studies suggest that this increase may be connected to the opioid epidemic, said Dr. Schuchat.

“People who inject drugs are 16% more likely to develop a staph infection” than are those who don’t inject drugs, she said.

Community-onset MRSA declined by 6.9% during 2001-2016, attributed to declines in health care–associated infections, according to Vital Signs author Athena P. Kourtis, MD, of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases, and her colleagues. Rates of hospital-associated MSSA infection remained essentially unchanged (P = .11). The overall unadjusted in-hospital mortality among patients with S. aureus bloodstream infections over the study period was 18%.

The data for the report were collected from electronic health records at more than 400 acute care hospitals, as well as population-based surveillance data from the CDC’s Emerging Infections Program.

Most people carry staph on their skin with no ill effects, but the bacteria become dangerous when they enter the bloodstream, Dr. Schuchat emphasized. “We hope the new data today will refocus the nation’s efforts to protect patients from staph infections,” she said.

SOURCE: Kourtis AP et al. MMWR. 2019 Mar 5; 68:1-6.

Serious infections from Staphylococcus aureus caused nearly 20,000 deaths and 119,000 illnesses in the United States in 2017, according to data from a Vital Signs report issued by the Centers for Disease Control and Prevention. The data include both methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA).

Although MRSA infections in health care settings declined by approximately 17% during 2005-2012, rates plateaued during 2012-2017, Anne Schuchat, MD, principal deputy director of the CDC, said in a teleconference March 5 to present the findings. The report emphasizes the potential for serious illness and death with any staph infection and the need for ongoing vigilance on the part of clinicians, she said.

In addition, community-onset MSSA infections increased by 3.9%/year during 2012-2017. Data from previous studies suggest that this increase may be connected to the opioid epidemic, said Dr. Schuchat.

“People who inject drugs are 16% more likely to develop a staph infection” than are those who don’t inject drugs, she said.

Community-onset MRSA declined by 6.9% during 2001-2016, attributed to declines in health care–associated infections, according to Vital Signs author Athena P. Kourtis, MD, of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases, and her colleagues. Rates of hospital-associated MSSA infection remained essentially unchanged (P = .11). The overall unadjusted in-hospital mortality among patients with S. aureus bloodstream infections over the study period was 18%.

The data for the report were collected from electronic health records at more than 400 acute care hospitals, as well as population-based surveillance data from the CDC’s Emerging Infections Program.

Most people carry staph on their skin with no ill effects, but the bacteria become dangerous when they enter the bloodstream, Dr. Schuchat emphasized. “We hope the new data today will refocus the nation’s efforts to protect patients from staph infections,” she said.

SOURCE: Kourtis AP et al. MMWR. 2019 Mar 5; 68:1-6.

Serious infections from Staphylococcus aureus caused nearly 20,000 deaths and 119,000 illnesses in the United States in 2017, according to data from a Vital Signs report issued by the Centers for Disease Control and Prevention. The data include both methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA).

Although MRSA infections in health care settings declined by approximately 17% during 2005-2012, rates plateaued during 2012-2017, Anne Schuchat, MD, principal deputy director of the CDC, said in a teleconference March 5 to present the findings. The report emphasizes the potential for serious illness and death with any staph infection and the need for ongoing vigilance on the part of clinicians, she said.

In addition, community-onset MSSA infections increased by 3.9%/year during 2012-2017. Data from previous studies suggest that this increase may be connected to the opioid epidemic, said Dr. Schuchat.

“People who inject drugs are 16% more likely to develop a staph infection” than are those who don’t inject drugs, she said.

Community-onset MRSA declined by 6.9% during 2001-2016, attributed to declines in health care–associated infections, according to Vital Signs author Athena P. Kourtis, MD, of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases, and her colleagues. Rates of hospital-associated MSSA infection remained essentially unchanged (P = .11). The overall unadjusted in-hospital mortality among patients with S. aureus bloodstream infections over the study period was 18%.

The data for the report were collected from electronic health records at more than 400 acute care hospitals, as well as population-based surveillance data from the CDC’s Emerging Infections Program.

Most people carry staph on their skin with no ill effects, but the bacteria become dangerous when they enter the bloodstream, Dr. Schuchat emphasized. “We hope the new data today will refocus the nation’s efforts to protect patients from staph infections,” she said.

SOURCE: Kourtis AP et al. MMWR. 2019 Mar 5; 68:1-6.

Resources

1. Kuehn BM. A proactive approach needed to combat rising STIs. JAMA. 2019;321:330-332.
2. Screening Recommendations and Considerations Referenced in Treatment Guidelines and Original Sources. Centers for Disease Control and Prevention. https://www.cdc.gov/std/tg2015/screening-recommendations.htm.  Updated June 4, 2015. Accessed February 27, 2019.
3. STD Clinical Consultation Network. National STD Curriculum. https://www.std.uw.edu/page/site/clinical-consultation. Accessed February 27, 2019.
4. National STD Curriculum. https://www.std.uw.edu/. Accessed February 27, 2019.
5. Sexually Transmitted Disease Surveillance 2017. Syphilis. Centers for Disease Control and Prevention. https://www.cdc.gov/std/stats17/syphilis.htm.  Reviewed July 24, 2018. Accessed February 27, 2019.

Resources

1. Kuehn BM. A proactive approach needed to combat rising STIs. JAMA. 2019;321:330-332.
2. Screening Recommendations and Considerations Referenced in Treatment Guidelines and Original Sources. Centers for Disease Control and Prevention. https://www.cdc.gov/std/tg2015/screening-recommendations.htm.  Updated June 4, 2015. Accessed February 27, 2019.
3. STD Clinical Consultation Network. National STD Curriculum. https://www.std.uw.edu/page/site/clinical-consultation. Accessed February 27, 2019.
4. National STD Curriculum. https://www.std.uw.edu/. Accessed February 27, 2019.
5. Sexually Transmitted Disease Surveillance 2017. Syphilis. Centers for Disease Control and Prevention. https://www.cdc.gov/std/stats17/syphilis.htm.  Reviewed July 24, 2018. Accessed February 27, 2019.

Resources

1. Kuehn BM. A proactive approach needed to combat rising STIs. JAMA. 2019;321:330-332.
2. Screening Recommendations and Considerations Referenced in Treatment Guidelines and Original Sources. Centers for Disease Control and Prevention. https://www.cdc.gov/std/tg2015/screening-recommendations.htm.  Updated June 4, 2015. Accessed February 27, 2019.
3. STD Clinical Consultation Network. National STD Curriculum. https://www.std.uw.edu/page/site/clinical-consultation. Accessed February 27, 2019.
4. National STD Curriculum. https://www.std.uw.edu/. Accessed February 27, 2019.
5. Sexually Transmitted Disease Surveillance 2017. Syphilis. Centers for Disease Control and Prevention. https://www.cdc.gov/std/stats17/syphilis.htm.  Reviewed July 24, 2018. Accessed February 27, 2019.

The last week of February added 47 new cases of measles and another state to the 10 that already have reported cases in 2019, according to the Centers for Disease Control and Prevention.

Those new cases represent a 30% increase in measles cases for the year, bringing the total to 206 reported to the CDC through Feb. 28. After just 2 months, 2019 has had more cases than all but 3 other years over the last decade, CDC data show.


The 11th state to report a case of measles this year is New Jersey, which joins California, Colorado, Connecticut, Georgia, Illinois (one outbreak), Kentucky, New York (three outbreaks), Oregon, Texas (one outbreak), and Washington (one outbreak), the CDC said.

The outbreak in Washington (4 new cases/70 for the year) had been the largest, but the majority of the new cases over the last 2 weeks have occurred in New York City, specifically Brooklyn, which reported 30 cases last week and 17 of the 32 new U.S. cases the week before.


Most of the 120 cases reported in the borough since the beginning of its outbreak in October of 2018 “have involved members of the Jewish Orthodox community. The initial child with measles was unvaccinated and acquired measles on a visit to Israel, where a large outbreak of the disease is occurring. Since then, there have been additional people from Brooklyn and Queens who were unvaccinated and acquired measles while in Israel. People who did not travel were also infected in Brooklyn or Rockland County,” the CDC said.

[email protected]

The last week of February added 47 new cases of measles and another state to the 10 that already have reported cases in 2019, according to the Centers for Disease Control and Prevention.

Those new cases represent a 30% increase in measles cases for the year, bringing the total to 206 reported to the CDC through Feb. 28. After just 2 months, 2019 has had more cases than all but 3 other years over the last decade, CDC data show.


The 11th state to report a case of measles this year is New Jersey, which joins California, Colorado, Connecticut, Georgia, Illinois (one outbreak), Kentucky, New York (three outbreaks), Oregon, Texas (one outbreak), and Washington (one outbreak), the CDC said.

The outbreak in Washington (4 new cases/70 for the year) had been the largest, but the majority of the new cases over the last 2 weeks have occurred in New York City, specifically Brooklyn, which reported 30 cases last week and 17 of the 32 new U.S. cases the week before.


Most of the 120 cases reported in the borough since the beginning of its outbreak in October of 2018 “have involved members of the Jewish Orthodox community. The initial child with measles was unvaccinated and acquired measles on a visit to Israel, where a large outbreak of the disease is occurring. Since then, there have been additional people from Brooklyn and Queens who were unvaccinated and acquired measles while in Israel. People who did not travel were also infected in Brooklyn or Rockland County,” the CDC said.

[email protected]

The last week of February added 47 new cases of measles and another state to the 10 that already have reported cases in 2019, according to the Centers for Disease Control and Prevention.

Those new cases represent a 30% increase in measles cases for the year, bringing the total to 206 reported to the CDC through Feb. 28. After just 2 months, 2019 has had more cases than all but 3 other years over the last decade, CDC data show.


The 11th state to report a case of measles this year is New Jersey, which joins California, Colorado, Connecticut, Georgia, Illinois (one outbreak), Kentucky, New York (three outbreaks), Oregon, Texas (one outbreak), and Washington (one outbreak), the CDC said.

The outbreak in Washington (4 new cases/70 for the year) had been the largest, but the majority of the new cases over the last 2 weeks have occurred in New York City, specifically Brooklyn, which reported 30 cases last week and 17 of the 32 new U.S. cases the week before.


Most of the 120 cases reported in the borough since the beginning of its outbreak in October of 2018 “have involved members of the Jewish Orthodox community. The initial child with measles was unvaccinated and acquired measles on a visit to Israel, where a large outbreak of the disease is occurring. Since then, there have been additional people from Brooklyn and Queens who were unvaccinated and acquired measles while in Israel. People who did not travel were also infected in Brooklyn or Rockland County,” the CDC said.

[email protected]