Physicians often encounter a “black box” in terms of where to focus their patient safety efforts. Obstetricians care for two patients – mothers and babies – simultaneously, which presents significant challenges. Safe obstetric care requires a multidisciplinary team with good communication skills. At the same time, gynecologic procedures are becoming more complex, and caring for a patient with complications can be quite challenging.

Breakdowns in communication often lead to adverse outcomes. Using closed obstetric malpractice claims allows practicing clinicians to understand where to focus their improvement efforts. The Doctors Company recently performed an analysis of 944 closed obstetric-gynecologic claims using a lexicon that is common to many other insurers. The study found that across patient claims, communication-related issues were common to nearly all allegations of ob.gyn.-related patient injury. The claims data revealed that key communication failures were in two major areas: communications with our patients and communication among team members, including the physician.

Physician-patient communication

Consider this example: Dr. S. is caring for a patient at term. At delivery, the infant has no heart rate and no respiratory effort and undergoes a full code and has APGAR scores of 0,0, and 3. While the indication for cesarean delivery was a nonreassuring fetal status, this was a surprising outcome. The team sent the placenta to the pathologist and there was an unusual finding of an amniotic web and the umbilical cord showed venous necrosis. A family meeting was held with the pathologist to explain the findings and the relationship to the baby’s need for support. While the presentation of the information did not change the outcome for the infant, it helped the patients and family to understand how the neonatal outcome occurred and that it was remote from delivery.

Common factors contributing to communication issues between physicians and patients/families include inadequate consent for treatment options; poor patient rapport, including unsympathetic responses to the patient; and language barriers, according to The Doctors Company’s clinical guide to improving patient safety and managing risks.

A fundamental step to address these factors is early education for patients and families about the risks and benefits of treatment, which is essential to reinforce understanding of potential interventions. Informed consent is a critical element of early education, but is often done in a rush, in a busy office setting – making it a critical risk factor. Having the informed consent conversation when the decision is made to go to surgery is important, but encouraging patients to bring forward questions and allowing their loved ones to have a clear understanding of their recovery process is also very helpful. When an unexpected complication occurs, having had a complete discussion about risks can help to mitigate an otherwise difficult situation.

We are often busy and stressed when complications arise, and the reflex is to withdraw from the patient who has suffered the complication. Demonstrating genuine empathy toward these patients allows the human side of physician-patient interaction to become apparent, which not only can reduce the patient’s and the family’s anger and frustration at a complicated situation but also can reduce the legal risk for the physician.
 

Provider communication

Consider another example: Ms. G is a 36-year old G1P0 who presented to the labor and delivery unit with severe preeclampsia. Failure to communicate a clear plan of action for management of her severe hypertension to all team members led to undertreated hypertension, a major stroke, and maternal death.

Both obstetrics and gynecology are specialties that require multidisciplinary teams, including nursing, anesthesia colleagues, consultants, and if at a teaching hospital, residents and medical and nursing students. Teamwork training initiatives can encourage providers to move out of their individual silos, practice more collaboratively, and share information across disciplines in a succinct and timely fashion. Understanding patients’ plans of care and competing resource demands allows a team to manage risk together.

Having a shared mental model and situation awareness across the team also creates a safety net for patients. This type of shared information is something highly reliable teams train on and communicate across disciplines, as this is not often taught in medical or nursing schools. Having clear roles and responsibilities allows professionals to create and understand expectations, especially around sharing safety concerns.

In situ simulations of high-risk situations both in labor and delivery and in the operating rooms are wonderful and instructive ways to practice teamwork behaviors. This type of exercise allows staff to practice skills together while discovering system failures in a nonthreatening environment. Later debriefing these activities allows staff to reflect on their own behavior and learn from one another, as well as to identify systems that need additional work.

Addressing patient safety risks effectively means focusing our energy and efforts toward underlying vulnerabilities that place patients at risk and increase liability for doctors. Sharing the results of lessons learned, through the evaluation of malpractice claims, helps to identify areas of vulnerabilities. Working to improve our communication with patients, families, and other providers, we can systematically lower risk to the patient and lower the risk of litigation to physicians.
 

Dr. Mann, an ob.gyn., is an assistant professor, part-time, at Harvard Medical School in Boston, and is a national consultant in patient safety and quality improvement in the field of obstetrics. She is a member of the Obstetrics Advisory Board of The Doctors Company. She is also a consultant at Harvard’s Risk Management Foundation, Dana-Farber Cancer Institute, and many institutions across the United States.

Physicians often encounter a “black box” in terms of where to focus their patient safety efforts. Obstetricians care for two patients – mothers and babies – simultaneously, which presents significant challenges. Safe obstetric care requires a multidisciplinary team with good communication skills. At the same time, gynecologic procedures are becoming more complex, and caring for a patient with complications can be quite challenging.

Breakdowns in communication often lead to adverse outcomes. Using closed obstetric malpractice claims allows practicing clinicians to understand where to focus their improvement efforts. The Doctors Company recently performed an analysis of 944 closed obstetric-gynecologic claims using a lexicon that is common to many other insurers. The study found that across patient claims, communication-related issues were common to nearly all allegations of ob.gyn.-related patient injury. The claims data revealed that key communication failures were in two major areas: communications with our patients and communication among team members, including the physician.

Physician-patient communication

Consider this example: Dr. S. is caring for a patient at term. At delivery, the infant has no heart rate and no respiratory effort and undergoes a full code and has APGAR scores of 0,0, and 3. While the indication for cesarean delivery was a nonreassuring fetal status, this was a surprising outcome. The team sent the placenta to the pathologist and there was an unusual finding of an amniotic web and the umbilical cord showed venous necrosis. A family meeting was held with the pathologist to explain the findings and the relationship to the baby’s need for support. While the presentation of the information did not change the outcome for the infant, it helped the patients and family to understand how the neonatal outcome occurred and that it was remote from delivery.

Common factors contributing to communication issues between physicians and patients/families include inadequate consent for treatment options; poor patient rapport, including unsympathetic responses to the patient; and language barriers, according to The Doctors Company’s clinical guide to improving patient safety and managing risks.

A fundamental step to address these factors is early education for patients and families about the risks and benefits of treatment, which is essential to reinforce understanding of potential interventions. Informed consent is a critical element of early education, but is often done in a rush, in a busy office setting – making it a critical risk factor. Having the informed consent conversation when the decision is made to go to surgery is important, but encouraging patients to bring forward questions and allowing their loved ones to have a clear understanding of their recovery process is also very helpful. When an unexpected complication occurs, having had a complete discussion about risks can help to mitigate an otherwise difficult situation.

We are often busy and stressed when complications arise, and the reflex is to withdraw from the patient who has suffered the complication. Demonstrating genuine empathy toward these patients allows the human side of physician-patient interaction to become apparent, which not only can reduce the patient’s and the family’s anger and frustration at a complicated situation but also can reduce the legal risk for the physician.
 

Provider communication

Consider another example: Ms. G is a 36-year old G1P0 who presented to the labor and delivery unit with severe preeclampsia. Failure to communicate a clear plan of action for management of her severe hypertension to all team members led to undertreated hypertension, a major stroke, and maternal death.

Both obstetrics and gynecology are specialties that require multidisciplinary teams, including nursing, anesthesia colleagues, consultants, and if at a teaching hospital, residents and medical and nursing students. Teamwork training initiatives can encourage providers to move out of their individual silos, practice more collaboratively, and share information across disciplines in a succinct and timely fashion. Understanding patients’ plans of care and competing resource demands allows a team to manage risk together.

Having a shared mental model and situation awareness across the team also creates a safety net for patients. This type of shared information is something highly reliable teams train on and communicate across disciplines, as this is not often taught in medical or nursing schools. Having clear roles and responsibilities allows professionals to create and understand expectations, especially around sharing safety concerns.

In situ simulations of high-risk situations both in labor and delivery and in the operating rooms are wonderful and instructive ways to practice teamwork behaviors. This type of exercise allows staff to practice skills together while discovering system failures in a nonthreatening environment. Later debriefing these activities allows staff to reflect on their own behavior and learn from one another, as well as to identify systems that need additional work.

Addressing patient safety risks effectively means focusing our energy and efforts toward underlying vulnerabilities that place patients at risk and increase liability for doctors. Sharing the results of lessons learned, through the evaluation of malpractice claims, helps to identify areas of vulnerabilities. Working to improve our communication with patients, families, and other providers, we can systematically lower risk to the patient and lower the risk of litigation to physicians.
 

Dr. Mann, an ob.gyn., is an assistant professor, part-time, at Harvard Medical School in Boston, and is a national consultant in patient safety and quality improvement in the field of obstetrics. She is a member of the Obstetrics Advisory Board of The Doctors Company. She is also a consultant at Harvard’s Risk Management Foundation, Dana-Farber Cancer Institute, and many institutions across the United States.

Physicians often encounter a “black box” in terms of where to focus their patient safety efforts. Obstetricians care for two patients – mothers and babies – simultaneously, which presents significant challenges. Safe obstetric care requires a multidisciplinary team with good communication skills. At the same time, gynecologic procedures are becoming more complex, and caring for a patient with complications can be quite challenging.

Breakdowns in communication often lead to adverse outcomes. Using closed obstetric malpractice claims allows practicing clinicians to understand where to focus their improvement efforts. The Doctors Company recently performed an analysis of 944 closed obstetric-gynecologic claims using a lexicon that is common to many other insurers. The study found that across patient claims, communication-related issues were common to nearly all allegations of ob.gyn.-related patient injury. The claims data revealed that key communication failures were in two major areas: communications with our patients and communication among team members, including the physician.

Physician-patient communication

Consider this example: Dr. S. is caring for a patient at term. At delivery, the infant has no heart rate and no respiratory effort and undergoes a full code and has APGAR scores of 0,0, and 3. While the indication for cesarean delivery was a nonreassuring fetal status, this was a surprising outcome. The team sent the placenta to the pathologist and there was an unusual finding of an amniotic web and the umbilical cord showed venous necrosis. A family meeting was held with the pathologist to explain the findings and the relationship to the baby’s need for support. While the presentation of the information did not change the outcome for the infant, it helped the patients and family to understand how the neonatal outcome occurred and that it was remote from delivery.

Common factors contributing to communication issues between physicians and patients/families include inadequate consent for treatment options; poor patient rapport, including unsympathetic responses to the patient; and language barriers, according to The Doctors Company’s clinical guide to improving patient safety and managing risks.

A fundamental step to address these factors is early education for patients and families about the risks and benefits of treatment, which is essential to reinforce understanding of potential interventions. Informed consent is a critical element of early education, but is often done in a rush, in a busy office setting – making it a critical risk factor. Having the informed consent conversation when the decision is made to go to surgery is important, but encouraging patients to bring forward questions and allowing their loved ones to have a clear understanding of their recovery process is also very helpful. When an unexpected complication occurs, having had a complete discussion about risks can help to mitigate an otherwise difficult situation.

We are often busy and stressed when complications arise, and the reflex is to withdraw from the patient who has suffered the complication. Demonstrating genuine empathy toward these patients allows the human side of physician-patient interaction to become apparent, which not only can reduce the patient’s and the family’s anger and frustration at a complicated situation but also can reduce the legal risk for the physician.
 

Provider communication

Consider another example: Ms. G is a 36-year old G1P0 who presented to the labor and delivery unit with severe preeclampsia. Failure to communicate a clear plan of action for management of her severe hypertension to all team members led to undertreated hypertension, a major stroke, and maternal death.

Both obstetrics and gynecology are specialties that require multidisciplinary teams, including nursing, anesthesia colleagues, consultants, and if at a teaching hospital, residents and medical and nursing students. Teamwork training initiatives can encourage providers to move out of their individual silos, practice more collaboratively, and share information across disciplines in a succinct and timely fashion. Understanding patients’ plans of care and competing resource demands allows a team to manage risk together.

Having a shared mental model and situation awareness across the team also creates a safety net for patients. This type of shared information is something highly reliable teams train on and communicate across disciplines, as this is not often taught in medical or nursing schools. Having clear roles and responsibilities allows professionals to create and understand expectations, especially around sharing safety concerns.

In situ simulations of high-risk situations both in labor and delivery and in the operating rooms are wonderful and instructive ways to practice teamwork behaviors. This type of exercise allows staff to practice skills together while discovering system failures in a nonthreatening environment. Later debriefing these activities allows staff to reflect on their own behavior and learn from one another, as well as to identify systems that need additional work.

Addressing patient safety risks effectively means focusing our energy and efforts toward underlying vulnerabilities that place patients at risk and increase liability for doctors. Sharing the results of lessons learned, through the evaluation of malpractice claims, helps to identify areas of vulnerabilities. Working to improve our communication with patients, families, and other providers, we can systematically lower risk to the patient and lower the risk of litigation to physicians.
 

Dr. Mann, an ob.gyn., is an assistant professor, part-time, at Harvard Medical School in Boston, and is a national consultant in patient safety and quality improvement in the field of obstetrics. She is a member of the Obstetrics Advisory Board of The Doctors Company. She is also a consultant at Harvard’s Risk Management Foundation, Dana-Farber Cancer Institute, and many institutions across the United States.

Methicillin-resistant Staphylococcus aureus (MRSA) is a Gram positive, round bacterium. The bacteria has evolved to withstand attacks from antibiotics and has made MRSA resistant to traditional antibiotics, such as β-lactams, resulting in difficult-to-treat infections. The presence of a genetic mutation within the mecA gene, which codes for the penicillin-binding protein 2a (PBP2a), differentiates MRSA from methicillin-susceptible Staphylococcus aureus (MSSA). Presence of the PBP2a protein allows Staphylococcus aureus (S aureus)to overcome β-lactam antibiotics’ method of killing by allowing the bacteria to continue to divide and grow.

β-lactam antibiotics cause cell death in susceptible isolates by binding to penicillin-binding proteins, which inhibits transpeptidation within the cell wall via inactivation of the penicillin-binding protein. By inhibiting cell wall synthesis, the cell loses its integrity and leaks its contents, causing cell death. Penicillin-binding protein 2a is a modified protein that has a low affinity for β-lactam antibiotics, allowing MRSA to survive and making it dangerous and difficult to eradicate.

First described in 1961, MRSA’s prevalence steadily increased in the following decades. It is the most common cause of skin and soft tissue infections presenting to emergency departments in the U.S.¹ About 20% of bloodstream infections are caused by S aureus, and in 2003, nearly two-thirds of hospital-onset S aureus infections were methicillin-resistant in U.S. intensive-care units (ICUs).² It has been shown that patients with MRSA bacteremia have worse overall outcomes, including increased mortality, greater lengths of stay, and increased costs, compared with those with MSSA infections.^2,3 In 2011, MRSA infections caused an estimated 11,000 deaths, making fast and accurate detection of MRSA a crucial step in appropriate antimicrobial therapy selection.⁴

Currently, the Clinical and Laboratory Standards Institute (CLSI) recommends testing for MRSA by using phenotypic or genotypic methods. Phenotypic methods test for the observable characteristics of an organism, whereas a genotypic method identifies the specific gene that the organism carries. Recommended phenotypic methods include the latex agglutination test for PBP2a, the cefoxitin disk screen test, and a plate containing 6 μg/mL of oxacillin in Mueller-Hinton agar supplemented with sodium chloride.⁵ These methods have varying sensitivity and specificity and take between 48 to 72 hours to provide a result.

Within the past 15 years, a newer, genotypic, method of MRSA detection was approved by the FDA with high sensitivity and specificity. This method uses polymerase chain reaction (PCR) to identify the mecA gene. Polymerase chain reaction is a technique used to copy and amplify a specific segment of DNA, making thousands to millions of copies. If present, the MRSA PCR amplifies the mecA gene that makes S aureus resistant to methicillin and other β-lactams, which confirms that the specimen contains MRSA. The FDA has approved the use of MRSA PCR nasal swabs to detect MRSA in patients at risk of nasal colonization. While previously discussed methods may take between 2 and 3 days to confirm presence of MRSA, PCR can identify MRSA in about 1 hour.⁶

If a S aureus infection is suspected, empiric therapy often includes coverage of both MSSA and MRSA, due to the high morbidity and mortality associated with these infections. However, continuing an unneeded or unduly broad antibiotic, such as those that cover MRSA, can cause unintended consequences, such as toxicities, emerging resistance, or selection for pathogenic organisms.⁷ Therefore, empiric broad antibiotic therapy should be de-escalated as soon as possible, which further emphasizes the need for quick and accurate detection of the infecting organism. De-escalation of therapy can lead to a shorter length of stay and decreased mortality.^8,9 Conversely, quick identification of infections caused by MRSA would allow therapy to be broadened to cover MRSA in infected patients, which could potentially decrease patient morbidity and mortality.

Nasal MRSA PCR Colonization

Rapid identification of a causative organism is crucial to determine appropriate antibiotic therapy. Fortunately, PCR is a very rapid method of detecting MRSA, and the use of MRSA PCR nasal swabs may be an effective way to predict whether MRSA is the organism causing an infection at various anatomical sites. If a patient has a suspected infection on admission, a MRSA PCR nasal swab often is completed to determine whether a patient’s nares are colonized with MRSA. However, there is no clear consensus in the literature regarding the correlation between MRSA nasal colonization and an infection caused by MRSA, making it difficult for clinicians to confidently de-escalate therapy on a negative MRSA PCR or broaden therapy on a positive result. The purpose of this literature review was to determine whether a MRSA PCR nasal swab can be used as a surrogate marker for MRSA infections at various sites.

Pneumonia has many potential causative organisms, many of which are covered empirically with guideline-directed therapy. The predictive power of MRSA PCR nasal swabs may allow clinicians to prescribe earlier directed therapy. A retrospective cohort study performed at a tertiary care center looked at the clinical usefulness of a MRSA PCR nasal swab in the treatment of pneumonia.¹⁰ Patients were included in the trial if they had a MRSA PCR nasal swab within 1 month of their blood or sputum culture as well as confirmed pneumonia. After analysis of 435 patients, the MRSA PCR nasal swab showed the following performance characteristics for detecting culture-proven MRSA: 88.0% sensitivity, 90.1% specificity, 35.4% positive predictive value (PPV), and 99.2% negative predictive value (NPV). Due to the high negative predictive value, the results indicated that discontinuation of MRSA antibiotic coverage would be appropriate for noncritically ill patients with pneumonia who had a negative MRSA PCR nasal swab.

Another retrospective study was performed by Johnson and colleagues to determine the association between MRSA PCR nasal swabs and the causative organism in pneumonia.¹¹ Patients were included in the trial if they had a MRSA PCR nasal swab and a lower respiratory culture yielding S aureus within 48 hours of hospital admission. After analysis of 72 patients, MRSA PCR nasal swabs demonstrated the following diagnostic characteristics for detecting culture-proven MRSA: 93.3% sensitivity, 95.2% specificity, 93.3%PPV, and 95.2% NPV. These results suggest that early nasal swab MRSA PCR tests can predict the absence of MRSA reliably and may help guide the discontinuation of MRSA-directed empiric antibiotic therapy.

In addition, Giancola retrospectively studied the relationship between MRSA PCR nasal swabs and the likelihood of pneumonia caused by MRSA in intensive and intermediate care units.¹² An analysis of 200 patients revealed high concordance between respiratory cultures and MRSA PCR nasal swab results with the following characteristics: 90.5% sensitivity, 79.9% specificity, 34.5% PPV, and 98.6% NPV. These test characteristics suggested that MRSA PCR nasal swabs might be a useful stewardship tool to allow for discontinuation of anti-MRSA therapy in critically ill patients with confirmed pneumonia.

Another retrospective analysis conducted by Baby and colleagues took a different approach to determine the clinical usefulness of MRSA PCR nasal swabs in the treatment of pneumonia.¹³ The primary outcome, mean duration of MRSA-targeted therapy, was reduced by 46.6 hours in the group who received a pharmacist-ordered MRSA PCR nasal swab compared with the group that did not receive a MRSA PCR nasal swab (P < .01) Per protocol, pharmacists were authorized to order a MRSA PCR nasal swab for patients who were prescribed vancomycin or linezolid for pneumonia. On receipt of the MRSA PCR nasal swab results, pharmacists were instructed to recommend discontinuation of anti-MRSA therapy if the PCR was negative for MRSA.

Results of this study indicated there were no significant differences in time to clinical improvement between preprotocol and postprotocol implementation (1.8 days vs 2.3 days, respectively; P = .54), length of stay (11.0 days vs 8.2 days, respectively; P = .22), or mortality (14.8% vs 6.7%, respectively; P = .41). The MRSA PCR nasal swabs allowed for a reduction in duration of anti-MRSA therapy without adverse effects on outcomes and provided a statistically significant reduction in the incidence of acute kidney injury during therapy in the postprotocol implementation group (26% vs 3.3%; P = .02), likely due to decreased exposure to vancomycin. Collectively, these studies indicate that MRSA PCR nasal swabs can be clinically useful in making decisions regarding discontinuation of MRSA-targeted therapy in pneumonia when MRSA PCR nasal swabs are negative.

A wider variety of infection sites were studied in a 2008 retrospective review of nearly 5,800 MRSA PCR nasal swabs taken within 24 hours (before or after) of a clinical culture that resulted growth of any organism.¹⁴ The goal of this study was to determine whether MRSA nasal colonization could predict MRSA involvement at various suspected infection sites. Overall, 217 patients (67.2%) with positive MRSA clinical cultures had a positive MRSA PCR nasal swab. The concordance between MRSA PCR nasal swabs and infection sites was highest with positive urine cultures (77%) and lowest in “other” infection sites (60%, primarily abdomen, buttock, and breast). Respiratory infections showed a 75% concordance between MRSA PCR nasal swabs and infection sites, as well as the following characteristics: 75% sensitivity, 90% specificity, 30% PPV, and 98% NPV. Additionally, infection site concordance was higher when clinical cultures grew clindamycin-resistant MRSA (71.3%) vs clindamycin-susceptible MRSA (59.3%; P = .04).

Overall, a positive MRSA PCR nasal swab increased the likelihood of MRSA at the primary infection site but was not clinically significant or consistent across infection sites. As seen in other studies, a negative MRSA PCR nasal swab could be useful for lowering concern for MRSA involvement in the primary infection, as evidenced by the following characteristics for all infection sites: 67% sensitivity, 90% specificity, 27% PPV, and 98% NPV.

Sarkionda and colleagues evaluated the clinical usefulness of MRSA PCR nasal swabs in the ICU setting in patients with a lower respiratory tract infection (RTI) or bloodstream infection.¹⁵ A total of 749 patients received a MRSA PCR nasal swab before admission to the ICU and were included in this study. The concordance between MRSA PCR nasal swabs and the causative organism was analyzed in patients who developed a MRSA lower respiratory infection (N = 120) and a MRSA bloodstream infection (N = 78) and demonstrated the following characteristics: 24.2% sensitivity, 78.5% specificity, 17.7% PPV, and 84.4% NPV; and 23.1% sensitivity, 78.2% specificity, 11.0% PPV, and 89.7% NPV, respectively. The authors concluded that the MRSA nasal swab results are not useful for making decisions regarding the need of empiric antimicrobial therapy targeting MRSA infections in lower respiratory infections and bloodstream infections. However, due to the high NPV in this study, one might conclude that negative MRSA PCR nasal swabs could still be used to de-escalate therapy, which is in agreement with the results from Dangerfield and Johnson.^10,11

Similarly, results from a retrospective chart review demonstrated a lack of predictive value by the MRSA PCR nasal swab.¹⁶ Of 1,203 adult patients admitted to an ICU at a single center, 57 positive MRSA colonized and 122 negative MRSA colonized patients’ charts were randomly selected. The presence of MRSA lower RTI or bloodstream infections was found to be 3.51% vs 2.46% in the colonized and noncolonized groups, respectively (P = .46). These results led to the conclusion that a positive MRSA PCR nasal swab alone should not be used to make decisions regarding empiric MRSA antibiotic coverage.

An alternative approach to MRSA surveillance was taken by Harris in a prospective cohort of 12,080 adults with a suspected infection on admission to a non-ICU.¹⁷ Patients were screened with a 2-question tool to determine whether they were high risk for a MRSA infection. The 2 questions were “Have you been admitted to any health care facility in the last 12 months?” and “Do you have a skin infection (eg, boil, abscess, spider bite, or cellulitis) at this time?” If patients answered yes to either question, they were considered high risk, and a MRSA PCR nasal swab was ordered.

Patients who answered no to both questions were considered low risk and did not receive a MRSA PCR nasal swab. In total, 623 of 5,609 patients (11.1%) identified as high risk had a positive MRSA PCR nasal swab, and 148 of these 623 patients (23.8%) developed a MRSA-positive clinical culture. Only 121 of 4,986 patients (2.4%) who were high risk and had a negative MRSA PCR nasal swab went on to develop a MRSA-positive clinical culture (98% NPV). Additionally, 104 of 6,741 patients (1.6%) who answered no to both screening questions developed a MRSA-positive clinical culture (98% NPV). Results indicated that a high percentage of patients who were at high risk for MRSA (yes response to either question) and had a positive MRSA PCR nasal swab also had a positive clinical culture for MRSA. Conversely, a very small percentage of high-risk patients with a negative MRSA PCR nasal swab developed a positive clinical culture for MRSA.

The screening tool proved very effective as the low-risk group had the lowest number of patients (1.6%) develop a positive clinical culture for MRSA. It may be deduced that combination use of MRSA colonization testing via PCR nasal swabs in conjunction with a screening tool may be an effective method to identify patients in whom anti-MRSA therapy can be safely discontinued.

Conclusion

Based on the results of previously described studies, sufficient data may exist to support the discontinuation of MRSA-targeted therapy in noncritically ill patients with confirmed or suspected pneumonia and a negative MRSA PCR nasal swab. Insufficient evidence exists, however, to support a broadening of antimicrobial therapy to include anti-MRSA coverage in individuals with a positive MRSA PCR nasal swab, regardless of the infection site.

Clinical judgment should be used when determining empiric antimicrobial therapy and for appropriateness of de-escalation of therapy in critically ill patients. Once a patient stabilizes, a negative MRSA PCR nasal swab could be considered as supporting evidence to discontinue anti-MRSA therapy, especially in patients with lower respiratory infections, such as pneumonia.

Methicillin-resistant Staphylococcus aureus (MRSA) is a Gram positive, round bacterium. The bacteria has evolved to withstand attacks from antibiotics and has made MRSA resistant to traditional antibiotics, such as β-lactams, resulting in difficult-to-treat infections. The presence of a genetic mutation within the mecA gene, which codes for the penicillin-binding protein 2a (PBP2a), differentiates MRSA from methicillin-susceptible Staphylococcus aureus (MSSA). Presence of the PBP2a protein allows Staphylococcus aureus (S aureus)to overcome β-lactam antibiotics’ method of killing by allowing the bacteria to continue to divide and grow.

β-lactam antibiotics cause cell death in susceptible isolates by binding to penicillin-binding proteins, which inhibits transpeptidation within the cell wall via inactivation of the penicillin-binding protein. By inhibiting cell wall synthesis, the cell loses its integrity and leaks its contents, causing cell death. Penicillin-binding protein 2a is a modified protein that has a low affinity for β-lactam antibiotics, allowing MRSA to survive and making it dangerous and difficult to eradicate.

First described in 1961, MRSA’s prevalence steadily increased in the following decades. It is the most common cause of skin and soft tissue infections presenting to emergency departments in the U.S.¹ About 20% of bloodstream infections are caused by S aureus, and in 2003, nearly two-thirds of hospital-onset S aureus infections were methicillin-resistant in U.S. intensive-care units (ICUs).² It has been shown that patients with MRSA bacteremia have worse overall outcomes, including increased mortality, greater lengths of stay, and increased costs, compared with those with MSSA infections.^2,3 In 2011, MRSA infections caused an estimated 11,000 deaths, making fast and accurate detection of MRSA a crucial step in appropriate antimicrobial therapy selection.⁴

Currently, the Clinical and Laboratory Standards Institute (CLSI) recommends testing for MRSA by using phenotypic or genotypic methods. Phenotypic methods test for the observable characteristics of an organism, whereas a genotypic method identifies the specific gene that the organism carries. Recommended phenotypic methods include the latex agglutination test for PBP2a, the cefoxitin disk screen test, and a plate containing 6 μg/mL of oxacillin in Mueller-Hinton agar supplemented with sodium chloride.⁵ These methods have varying sensitivity and specificity and take between 48 to 72 hours to provide a result.

Within the past 15 years, a newer, genotypic, method of MRSA detection was approved by the FDA with high sensitivity and specificity. This method uses polymerase chain reaction (PCR) to identify the mecA gene. Polymerase chain reaction is a technique used to copy and amplify a specific segment of DNA, making thousands to millions of copies. If present, the MRSA PCR amplifies the mecA gene that makes S aureus resistant to methicillin and other β-lactams, which confirms that the specimen contains MRSA. The FDA has approved the use of MRSA PCR nasal swabs to detect MRSA in patients at risk of nasal colonization. While previously discussed methods may take between 2 and 3 days to confirm presence of MRSA, PCR can identify MRSA in about 1 hour.⁶

If a S aureus infection is suspected, empiric therapy often includes coverage of both MSSA and MRSA, due to the high morbidity and mortality associated with these infections. However, continuing an unneeded or unduly broad antibiotic, such as those that cover MRSA, can cause unintended consequences, such as toxicities, emerging resistance, or selection for pathogenic organisms.⁷ Therefore, empiric broad antibiotic therapy should be de-escalated as soon as possible, which further emphasizes the need for quick and accurate detection of the infecting organism. De-escalation of therapy can lead to a shorter length of stay and decreased mortality.^8,9 Conversely, quick identification of infections caused by MRSA would allow therapy to be broadened to cover MRSA in infected patients, which could potentially decrease patient morbidity and mortality.

Nasal MRSA PCR Colonization

Rapid identification of a causative organism is crucial to determine appropriate antibiotic therapy. Fortunately, PCR is a very rapid method of detecting MRSA, and the use of MRSA PCR nasal swabs may be an effective way to predict whether MRSA is the organism causing an infection at various anatomical sites. If a patient has a suspected infection on admission, a MRSA PCR nasal swab often is completed to determine whether a patient’s nares are colonized with MRSA. However, there is no clear consensus in the literature regarding the correlation between MRSA nasal colonization and an infection caused by MRSA, making it difficult for clinicians to confidently de-escalate therapy on a negative MRSA PCR or broaden therapy on a positive result. The purpose of this literature review was to determine whether a MRSA PCR nasal swab can be used as a surrogate marker for MRSA infections at various sites.

Pneumonia has many potential causative organisms, many of which are covered empirically with guideline-directed therapy. The predictive power of MRSA PCR nasal swabs may allow clinicians to prescribe earlier directed therapy. A retrospective cohort study performed at a tertiary care center looked at the clinical usefulness of a MRSA PCR nasal swab in the treatment of pneumonia.¹⁰ Patients were included in the trial if they had a MRSA PCR nasal swab within 1 month of their blood or sputum culture as well as confirmed pneumonia. After analysis of 435 patients, the MRSA PCR nasal swab showed the following performance characteristics for detecting culture-proven MRSA: 88.0% sensitivity, 90.1% specificity, 35.4% positive predictive value (PPV), and 99.2% negative predictive value (NPV). Due to the high negative predictive value, the results indicated that discontinuation of MRSA antibiotic coverage would be appropriate for noncritically ill patients with pneumonia who had a negative MRSA PCR nasal swab.

Another retrospective study was performed by Johnson and colleagues to determine the association between MRSA PCR nasal swabs and the causative organism in pneumonia.¹¹ Patients were included in the trial if they had a MRSA PCR nasal swab and a lower respiratory culture yielding S aureus within 48 hours of hospital admission. After analysis of 72 patients, MRSA PCR nasal swabs demonstrated the following diagnostic characteristics for detecting culture-proven MRSA: 93.3% sensitivity, 95.2% specificity, 93.3%PPV, and 95.2% NPV. These results suggest that early nasal swab MRSA PCR tests can predict the absence of MRSA reliably and may help guide the discontinuation of MRSA-directed empiric antibiotic therapy.

In addition, Giancola retrospectively studied the relationship between MRSA PCR nasal swabs and the likelihood of pneumonia caused by MRSA in intensive and intermediate care units.¹² An analysis of 200 patients revealed high concordance between respiratory cultures and MRSA PCR nasal swab results with the following characteristics: 90.5% sensitivity, 79.9% specificity, 34.5% PPV, and 98.6% NPV. These test characteristics suggested that MRSA PCR nasal swabs might be a useful stewardship tool to allow for discontinuation of anti-MRSA therapy in critically ill patients with confirmed pneumonia.

Another retrospective analysis conducted by Baby and colleagues took a different approach to determine the clinical usefulness of MRSA PCR nasal swabs in the treatment of pneumonia.¹³ The primary outcome, mean duration of MRSA-targeted therapy, was reduced by 46.6 hours in the group who received a pharmacist-ordered MRSA PCR nasal swab compared with the group that did not receive a MRSA PCR nasal swab (P < .01) Per protocol, pharmacists were authorized to order a MRSA PCR nasal swab for patients who were prescribed vancomycin or linezolid for pneumonia. On receipt of the MRSA PCR nasal swab results, pharmacists were instructed to recommend discontinuation of anti-MRSA therapy if the PCR was negative for MRSA.

Results of this study indicated there were no significant differences in time to clinical improvement between preprotocol and postprotocol implementation (1.8 days vs 2.3 days, respectively; P = .54), length of stay (11.0 days vs 8.2 days, respectively; P = .22), or mortality (14.8% vs 6.7%, respectively; P = .41). The MRSA PCR nasal swabs allowed for a reduction in duration of anti-MRSA therapy without adverse effects on outcomes and provided a statistically significant reduction in the incidence of acute kidney injury during therapy in the postprotocol implementation group (26% vs 3.3%; P = .02), likely due to decreased exposure to vancomycin. Collectively, these studies indicate that MRSA PCR nasal swabs can be clinically useful in making decisions regarding discontinuation of MRSA-targeted therapy in pneumonia when MRSA PCR nasal swabs are negative.

A wider variety of infection sites were studied in a 2008 retrospective review of nearly 5,800 MRSA PCR nasal swabs taken within 24 hours (before or after) of a clinical culture that resulted growth of any organism.¹⁴ The goal of this study was to determine whether MRSA nasal colonization could predict MRSA involvement at various suspected infection sites. Overall, 217 patients (67.2%) with positive MRSA clinical cultures had a positive MRSA PCR nasal swab. The concordance between MRSA PCR nasal swabs and infection sites was highest with positive urine cultures (77%) and lowest in “other” infection sites (60%, primarily abdomen, buttock, and breast). Respiratory infections showed a 75% concordance between MRSA PCR nasal swabs and infection sites, as well as the following characteristics: 75% sensitivity, 90% specificity, 30% PPV, and 98% NPV. Additionally, infection site concordance was higher when clinical cultures grew clindamycin-resistant MRSA (71.3%) vs clindamycin-susceptible MRSA (59.3%; P = .04).

Overall, a positive MRSA PCR nasal swab increased the likelihood of MRSA at the primary infection site but was not clinically significant or consistent across infection sites. As seen in other studies, a negative MRSA PCR nasal swab could be useful for lowering concern for MRSA involvement in the primary infection, as evidenced by the following characteristics for all infection sites: 67% sensitivity, 90% specificity, 27% PPV, and 98% NPV.

Sarkionda and colleagues evaluated the clinical usefulness of MRSA PCR nasal swabs in the ICU setting in patients with a lower respiratory tract infection (RTI) or bloodstream infection.¹⁵ A total of 749 patients received a MRSA PCR nasal swab before admission to the ICU and were included in this study. The concordance between MRSA PCR nasal swabs and the causative organism was analyzed in patients who developed a MRSA lower respiratory infection (N = 120) and a MRSA bloodstream infection (N = 78) and demonstrated the following characteristics: 24.2% sensitivity, 78.5% specificity, 17.7% PPV, and 84.4% NPV; and 23.1% sensitivity, 78.2% specificity, 11.0% PPV, and 89.7% NPV, respectively. The authors concluded that the MRSA nasal swab results are not useful for making decisions regarding the need of empiric antimicrobial therapy targeting MRSA infections in lower respiratory infections and bloodstream infections. However, due to the high NPV in this study, one might conclude that negative MRSA PCR nasal swabs could still be used to de-escalate therapy, which is in agreement with the results from Dangerfield and Johnson.^10,11

Similarly, results from a retrospective chart review demonstrated a lack of predictive value by the MRSA PCR nasal swab.¹⁶ Of 1,203 adult patients admitted to an ICU at a single center, 57 positive MRSA colonized and 122 negative MRSA colonized patients’ charts were randomly selected. The presence of MRSA lower RTI or bloodstream infections was found to be 3.51% vs 2.46% in the colonized and noncolonized groups, respectively (P = .46). These results led to the conclusion that a positive MRSA PCR nasal swab alone should not be used to make decisions regarding empiric MRSA antibiotic coverage.

An alternative approach to MRSA surveillance was taken by Harris in a prospective cohort of 12,080 adults with a suspected infection on admission to a non-ICU.¹⁷ Patients were screened with a 2-question tool to determine whether they were high risk for a MRSA infection. The 2 questions were “Have you been admitted to any health care facility in the last 12 months?” and “Do you have a skin infection (eg, boil, abscess, spider bite, or cellulitis) at this time?” If patients answered yes to either question, they were considered high risk, and a MRSA PCR nasal swab was ordered.

Patients who answered no to both questions were considered low risk and did not receive a MRSA PCR nasal swab. In total, 623 of 5,609 patients (11.1%) identified as high risk had a positive MRSA PCR nasal swab, and 148 of these 623 patients (23.8%) developed a MRSA-positive clinical culture. Only 121 of 4,986 patients (2.4%) who were high risk and had a negative MRSA PCR nasal swab went on to develop a MRSA-positive clinical culture (98% NPV). Additionally, 104 of 6,741 patients (1.6%) who answered no to both screening questions developed a MRSA-positive clinical culture (98% NPV). Results indicated that a high percentage of patients who were at high risk for MRSA (yes response to either question) and had a positive MRSA PCR nasal swab also had a positive clinical culture for MRSA. Conversely, a very small percentage of high-risk patients with a negative MRSA PCR nasal swab developed a positive clinical culture for MRSA.

The screening tool proved very effective as the low-risk group had the lowest number of patients (1.6%) develop a positive clinical culture for MRSA. It may be deduced that combination use of MRSA colonization testing via PCR nasal swabs in conjunction with a screening tool may be an effective method to identify patients in whom anti-MRSA therapy can be safely discontinued.

Conclusion

Based on the results of previously described studies, sufficient data may exist to support the discontinuation of MRSA-targeted therapy in noncritically ill patients with confirmed or suspected pneumonia and a negative MRSA PCR nasal swab. Insufficient evidence exists, however, to support a broadening of antimicrobial therapy to include anti-MRSA coverage in individuals with a positive MRSA PCR nasal swab, regardless of the infection site.

Clinical judgment should be used when determining empiric antimicrobial therapy and for appropriateness of de-escalation of therapy in critically ill patients. Once a patient stabilizes, a negative MRSA PCR nasal swab could be considered as supporting evidence to discontinue anti-MRSA therapy, especially in patients with lower respiratory infections, such as pneumonia.

Methicillin-resistant Staphylococcus aureus (MRSA) is a Gram positive, round bacterium. The bacteria has evolved to withstand attacks from antibiotics and has made MRSA resistant to traditional antibiotics, such as β-lactams, resulting in difficult-to-treat infections. The presence of a genetic mutation within the mecA gene, which codes for the penicillin-binding protein 2a (PBP2a), differentiates MRSA from methicillin-susceptible Staphylococcus aureus (MSSA). Presence of the PBP2a protein allows Staphylococcus aureus (S aureus)to overcome β-lactam antibiotics’ method of killing by allowing the bacteria to continue to divide and grow.

β-lactam antibiotics cause cell death in susceptible isolates by binding to penicillin-binding proteins, which inhibits transpeptidation within the cell wall via inactivation of the penicillin-binding protein. By inhibiting cell wall synthesis, the cell loses its integrity and leaks its contents, causing cell death. Penicillin-binding protein 2a is a modified protein that has a low affinity for β-lactam antibiotics, allowing MRSA to survive and making it dangerous and difficult to eradicate.

First described in 1961, MRSA’s prevalence steadily increased in the following decades. It is the most common cause of skin and soft tissue infections presenting to emergency departments in the U.S.¹ About 20% of bloodstream infections are caused by S aureus, and in 2003, nearly two-thirds of hospital-onset S aureus infections were methicillin-resistant in U.S. intensive-care units (ICUs).² It has been shown that patients with MRSA bacteremia have worse overall outcomes, including increased mortality, greater lengths of stay, and increased costs, compared with those with MSSA infections.^2,3 In 2011, MRSA infections caused an estimated 11,000 deaths, making fast and accurate detection of MRSA a crucial step in appropriate antimicrobial therapy selection.⁴

Currently, the Clinical and Laboratory Standards Institute (CLSI) recommends testing for MRSA by using phenotypic or genotypic methods. Phenotypic methods test for the observable characteristics of an organism, whereas a genotypic method identifies the specific gene that the organism carries. Recommended phenotypic methods include the latex agglutination test for PBP2a, the cefoxitin disk screen test, and a plate containing 6 μg/mL of oxacillin in Mueller-Hinton agar supplemented with sodium chloride.⁵ These methods have varying sensitivity and specificity and take between 48 to 72 hours to provide a result.

Within the past 15 years, a newer, genotypic, method of MRSA detection was approved by the FDA with high sensitivity and specificity. This method uses polymerase chain reaction (PCR) to identify the mecA gene. Polymerase chain reaction is a technique used to copy and amplify a specific segment of DNA, making thousands to millions of copies. If present, the MRSA PCR amplifies the mecA gene that makes S aureus resistant to methicillin and other β-lactams, which confirms that the specimen contains MRSA. The FDA has approved the use of MRSA PCR nasal swabs to detect MRSA in patients at risk of nasal colonization. While previously discussed methods may take between 2 and 3 days to confirm presence of MRSA, PCR can identify MRSA in about 1 hour.⁶

If a S aureus infection is suspected, empiric therapy often includes coverage of both MSSA and MRSA, due to the high morbidity and mortality associated with these infections. However, continuing an unneeded or unduly broad antibiotic, such as those that cover MRSA, can cause unintended consequences, such as toxicities, emerging resistance, or selection for pathogenic organisms.⁷ Therefore, empiric broad antibiotic therapy should be de-escalated as soon as possible, which further emphasizes the need for quick and accurate detection of the infecting organism. De-escalation of therapy can lead to a shorter length of stay and decreased mortality.^8,9 Conversely, quick identification of infections caused by MRSA would allow therapy to be broadened to cover MRSA in infected patients, which could potentially decrease patient morbidity and mortality.

Nasal MRSA PCR Colonization

Rapid identification of a causative organism is crucial to determine appropriate antibiotic therapy. Fortunately, PCR is a very rapid method of detecting MRSA, and the use of MRSA PCR nasal swabs may be an effective way to predict whether MRSA is the organism causing an infection at various anatomical sites. If a patient has a suspected infection on admission, a MRSA PCR nasal swab often is completed to determine whether a patient’s nares are colonized with MRSA. However, there is no clear consensus in the literature regarding the correlation between MRSA nasal colonization and an infection caused by MRSA, making it difficult for clinicians to confidently de-escalate therapy on a negative MRSA PCR or broaden therapy on a positive result. The purpose of this literature review was to determine whether a MRSA PCR nasal swab can be used as a surrogate marker for MRSA infections at various sites.

Pneumonia has many potential causative organisms, many of which are covered empirically with guideline-directed therapy. The predictive power of MRSA PCR nasal swabs may allow clinicians to prescribe earlier directed therapy. A retrospective cohort study performed at a tertiary care center looked at the clinical usefulness of a MRSA PCR nasal swab in the treatment of pneumonia.¹⁰ Patients were included in the trial if they had a MRSA PCR nasal swab within 1 month of their blood or sputum culture as well as confirmed pneumonia. After analysis of 435 patients, the MRSA PCR nasal swab showed the following performance characteristics for detecting culture-proven MRSA: 88.0% sensitivity, 90.1% specificity, 35.4% positive predictive value (PPV), and 99.2% negative predictive value (NPV). Due to the high negative predictive value, the results indicated that discontinuation of MRSA antibiotic coverage would be appropriate for noncritically ill patients with pneumonia who had a negative MRSA PCR nasal swab.

Another retrospective study was performed by Johnson and colleagues to determine the association between MRSA PCR nasal swabs and the causative organism in pneumonia.¹¹ Patients were included in the trial if they had a MRSA PCR nasal swab and a lower respiratory culture yielding S aureus within 48 hours of hospital admission. After analysis of 72 patients, MRSA PCR nasal swabs demonstrated the following diagnostic characteristics for detecting culture-proven MRSA: 93.3% sensitivity, 95.2% specificity, 93.3%PPV, and 95.2% NPV. These results suggest that early nasal swab MRSA PCR tests can predict the absence of MRSA reliably and may help guide the discontinuation of MRSA-directed empiric antibiotic therapy.

In addition, Giancola retrospectively studied the relationship between MRSA PCR nasal swabs and the likelihood of pneumonia caused by MRSA in intensive and intermediate care units.¹² An analysis of 200 patients revealed high concordance between respiratory cultures and MRSA PCR nasal swab results with the following characteristics: 90.5% sensitivity, 79.9% specificity, 34.5% PPV, and 98.6% NPV. These test characteristics suggested that MRSA PCR nasal swabs might be a useful stewardship tool to allow for discontinuation of anti-MRSA therapy in critically ill patients with confirmed pneumonia.

Another retrospective analysis conducted by Baby and colleagues took a different approach to determine the clinical usefulness of MRSA PCR nasal swabs in the treatment of pneumonia.¹³ The primary outcome, mean duration of MRSA-targeted therapy, was reduced by 46.6 hours in the group who received a pharmacist-ordered MRSA PCR nasal swab compared with the group that did not receive a MRSA PCR nasal swab (P < .01) Per protocol, pharmacists were authorized to order a MRSA PCR nasal swab for patients who were prescribed vancomycin or linezolid for pneumonia. On receipt of the MRSA PCR nasal swab results, pharmacists were instructed to recommend discontinuation of anti-MRSA therapy if the PCR was negative for MRSA.

Results of this study indicated there were no significant differences in time to clinical improvement between preprotocol and postprotocol implementation (1.8 days vs 2.3 days, respectively; P = .54), length of stay (11.0 days vs 8.2 days, respectively; P = .22), or mortality (14.8% vs 6.7%, respectively; P = .41). The MRSA PCR nasal swabs allowed for a reduction in duration of anti-MRSA therapy without adverse effects on outcomes and provided a statistically significant reduction in the incidence of acute kidney injury during therapy in the postprotocol implementation group (26% vs 3.3%; P = .02), likely due to decreased exposure to vancomycin. Collectively, these studies indicate that MRSA PCR nasal swabs can be clinically useful in making decisions regarding discontinuation of MRSA-targeted therapy in pneumonia when MRSA PCR nasal swabs are negative.

A wider variety of infection sites were studied in a 2008 retrospective review of nearly 5,800 MRSA PCR nasal swabs taken within 24 hours (before or after) of a clinical culture that resulted growth of any organism.¹⁴ The goal of this study was to determine whether MRSA nasal colonization could predict MRSA involvement at various suspected infection sites. Overall, 217 patients (67.2%) with positive MRSA clinical cultures had a positive MRSA PCR nasal swab. The concordance between MRSA PCR nasal swabs and infection sites was highest with positive urine cultures (77%) and lowest in “other” infection sites (60%, primarily abdomen, buttock, and breast). Respiratory infections showed a 75% concordance between MRSA PCR nasal swabs and infection sites, as well as the following characteristics: 75% sensitivity, 90% specificity, 30% PPV, and 98% NPV. Additionally, infection site concordance was higher when clinical cultures grew clindamycin-resistant MRSA (71.3%) vs clindamycin-susceptible MRSA (59.3%; P = .04).

Overall, a positive MRSA PCR nasal swab increased the likelihood of MRSA at the primary infection site but was not clinically significant or consistent across infection sites. As seen in other studies, a negative MRSA PCR nasal swab could be useful for lowering concern for MRSA involvement in the primary infection, as evidenced by the following characteristics for all infection sites: 67% sensitivity, 90% specificity, 27% PPV, and 98% NPV.

Sarkionda and colleagues evaluated the clinical usefulness of MRSA PCR nasal swabs in the ICU setting in patients with a lower respiratory tract infection (RTI) or bloodstream infection.¹⁵ A total of 749 patients received a MRSA PCR nasal swab before admission to the ICU and were included in this study. The concordance between MRSA PCR nasal swabs and the causative organism was analyzed in patients who developed a MRSA lower respiratory infection (N = 120) and a MRSA bloodstream infection (N = 78) and demonstrated the following characteristics: 24.2% sensitivity, 78.5% specificity, 17.7% PPV, and 84.4% NPV; and 23.1% sensitivity, 78.2% specificity, 11.0% PPV, and 89.7% NPV, respectively. The authors concluded that the MRSA nasal swab results are not useful for making decisions regarding the need of empiric antimicrobial therapy targeting MRSA infections in lower respiratory infections and bloodstream infections. However, due to the high NPV in this study, one might conclude that negative MRSA PCR nasal swabs could still be used to de-escalate therapy, which is in agreement with the results from Dangerfield and Johnson.^10,11

Similarly, results from a retrospective chart review demonstrated a lack of predictive value by the MRSA PCR nasal swab.¹⁶ Of 1,203 adult patients admitted to an ICU at a single center, 57 positive MRSA colonized and 122 negative MRSA colonized patients’ charts were randomly selected. The presence of MRSA lower RTI or bloodstream infections was found to be 3.51% vs 2.46% in the colonized and noncolonized groups, respectively (P = .46). These results led to the conclusion that a positive MRSA PCR nasal swab alone should not be used to make decisions regarding empiric MRSA antibiotic coverage.

An alternative approach to MRSA surveillance was taken by Harris in a prospective cohort of 12,080 adults with a suspected infection on admission to a non-ICU.¹⁷ Patients were screened with a 2-question tool to determine whether they were high risk for a MRSA infection. The 2 questions were “Have you been admitted to any health care facility in the last 12 months?” and “Do you have a skin infection (eg, boil, abscess, spider bite, or cellulitis) at this time?” If patients answered yes to either question, they were considered high risk, and a MRSA PCR nasal swab was ordered.

Patients who answered no to both questions were considered low risk and did not receive a MRSA PCR nasal swab. In total, 623 of 5,609 patients (11.1%) identified as high risk had a positive MRSA PCR nasal swab, and 148 of these 623 patients (23.8%) developed a MRSA-positive clinical culture. Only 121 of 4,986 patients (2.4%) who were high risk and had a negative MRSA PCR nasal swab went on to develop a MRSA-positive clinical culture (98% NPV). Additionally, 104 of 6,741 patients (1.6%) who answered no to both screening questions developed a MRSA-positive clinical culture (98% NPV). Results indicated that a high percentage of patients who were at high risk for MRSA (yes response to either question) and had a positive MRSA PCR nasal swab also had a positive clinical culture for MRSA. Conversely, a very small percentage of high-risk patients with a negative MRSA PCR nasal swab developed a positive clinical culture for MRSA.

The screening tool proved very effective as the low-risk group had the lowest number of patients (1.6%) develop a positive clinical culture for MRSA. It may be deduced that combination use of MRSA colonization testing via PCR nasal swabs in conjunction with a screening tool may be an effective method to identify patients in whom anti-MRSA therapy can be safely discontinued.

Conclusion

Based on the results of previously described studies, sufficient data may exist to support the discontinuation of MRSA-targeted therapy in noncritically ill patients with confirmed or suspected pneumonia and a negative MRSA PCR nasal swab. Insufficient evidence exists, however, to support a broadening of antimicrobial therapy to include anti-MRSA coverage in individuals with a positive MRSA PCR nasal swab, regardless of the infection site.

Clinical judgment should be used when determining empiric antimicrobial therapy and for appropriateness of de-escalation of therapy in critically ill patients. Once a patient stabilizes, a negative MRSA PCR nasal swab could be considered as supporting evidence to discontinue anti-MRSA therapy, especially in patients with lower respiratory infections, such as pneumonia.

Patients with diabetes—especially the elderly—are at high risk for morbidity and mortality due to cancer, studies have shown. Researchers from Specialist District Hospital and University of Rzeszow in Poland say their study “sheds some new light” in demonstrating another kind of association between diabetes and cancer in older patients: a higher risk of hospitalization with surgery due to cancer.

They analyzed data on 7,694 patients aged > 45 years hospitalized in a surgery ward. Of those, 652 were diagnosed with cancer and 370 with diabetes; 93 patients had both. The most common kind of cancer was urinary bladder cancer. The researchers note that their surgical unit has a large urology subdivision. Patients with other site-specific cancers are usually referred to more specialized clinical units.

Diabetes was the strongest predictor of risk among the variables analyzed, although urban residence also was a significant predictor. Risk of hospitalization due to cancer doubled among diabetic patients aged 45 to  65 years and was > 5 times higher among patients aged > 65 years, compared with the nondiabetic patients. The highest risk of hospitalization for site-specific cancers was among patients with kidney and breast cancers.

The researchers say their findings suggest that it is “advisable to make major efforts” for early detection and early radical treatment in older patients with diabetes. 

Source:

Dᾳbrowski M, Grindecka A. Arch Med Sci. 2017;13(5):1025-1030.
doi: 10.5114/aoms.2016.58666.

Patients with diabetes—especially the elderly—are at high risk for morbidity and mortality due to cancer, studies have shown. Researchers from Specialist District Hospital and University of Rzeszow in Poland say their study “sheds some new light” in demonstrating another kind of association between diabetes and cancer in older patients: a higher risk of hospitalization with surgery due to cancer.

They analyzed data on 7,694 patients aged > 45 years hospitalized in a surgery ward. Of those, 652 were diagnosed with cancer and 370 with diabetes; 93 patients had both. The most common kind of cancer was urinary bladder cancer. The researchers note that their surgical unit has a large urology subdivision. Patients with other site-specific cancers are usually referred to more specialized clinical units.

Diabetes was the strongest predictor of risk among the variables analyzed, although urban residence also was a significant predictor. Risk of hospitalization due to cancer doubled among diabetic patients aged 45 to  65 years and was > 5 times higher among patients aged > 65 years, compared with the nondiabetic patients. The highest risk of hospitalization for site-specific cancers was among patients with kidney and breast cancers.

The researchers say their findings suggest that it is “advisable to make major efforts” for early detection and early radical treatment in older patients with diabetes. 

Source:

Dᾳbrowski M, Grindecka A. Arch Med Sci. 2017;13(5):1025-1030.
doi: 10.5114/aoms.2016.58666.

Patients with diabetes—especially the elderly—are at high risk for morbidity and mortality due to cancer, studies have shown. Researchers from Specialist District Hospital and University of Rzeszow in Poland say their study “sheds some new light” in demonstrating another kind of association between diabetes and cancer in older patients: a higher risk of hospitalization with surgery due to cancer.

They analyzed data on 7,694 patients aged > 45 years hospitalized in a surgery ward. Of those, 652 were diagnosed with cancer and 370 with diabetes; 93 patients had both. The most common kind of cancer was urinary bladder cancer. The researchers note that their surgical unit has a large urology subdivision. Patients with other site-specific cancers are usually referred to more specialized clinical units.

Diabetes was the strongest predictor of risk among the variables analyzed, although urban residence also was a significant predictor. Risk of hospitalization due to cancer doubled among diabetic patients aged 45 to  65 years and was > 5 times higher among patients aged > 65 years, compared with the nondiabetic patients. The highest risk of hospitalization for site-specific cancers was among patients with kidney and breast cancers.

The researchers say their findings suggest that it is “advisable to make major efforts” for early detection and early radical treatment in older patients with diabetes. 

Source:

Dᾳbrowski M, Grindecka A. Arch Med Sci. 2017;13(5):1025-1030.
doi: 10.5114/aoms.2016.58666.

Photo by Bill Branson

The US Food and Drug Administration (FDA) has approved inotuzumab ozogamicin (Besponsa®) for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

The labeling for inotuzumab ozogamicin includes a boxed warning stating that the drug poses a risk of hepatotoxicity, including hepatic veno-occlusive disease (or sinusoidal obstruction syndrome), as well as an increased risk of post-transplant non-relapse mortality.

The full prescribing information for inotuzumab ozogamicin is available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761040s000lbl.pdf.

Inotuzumab ozogamicin is an antibody-drug conjugate that consists of a monoclonal antibody targeting CD22 and a cytotoxic agent known as calicheamicin.

The product originates from a collaboration between Pfizer and Celltech (now UCB), but Pfizer has sole responsibility for all manufacturing and clinical development activities.

Inotuzumab ozogamicin was reviewed and approved under the FDA’s breakthrough therapy designation and priority review programs.

The application for inotuzumab ozogamicin was supported by results from the phase 3 INO-VATE trial, which were published in NEJM in June 2016.

The trial enrolled 326 adults with relapsed or refractory B-cell ALL. Patients received inotuzumab ozogamicin or 1 of 3 chemotherapy regimens (high-dose cytarabine, cytarabine plus mitoxantrone, or fludarabine, cytarabine, and granulocyte colony-stimulating factor).

The rate of complete remission, including incomplete hematologic recovery, was 80.7% in the inotuzumab arm and 29.4% in the chemotherapy arm (P<0.001). The median duration of remission was 4.6 months and 3.1 months, respectively (P=0.03).

Forty-one percent of patients treated with inotuzumab and 11% of those who received chemotherapy proceeded to stem cell transplant directly after treatment (P<0.001).

The median progression-free survival was 5.0 months in the inotuzumab arm and 1.8 months in the chemotherapy arm (P<0.001).

The median overall survival was 7.7 months and 6.7 months, respectively (P=0.04). This did not meet the prespecified boundary of significance (P=0.0208).

Liver-related adverse events were more common in the inotuzumab arm than the chemotherapy arm. The most frequent of these were increased aspartate aminotransferase level (20% vs 10%), hyperbilirubinemia (15% vs 10%), and increased alanine aminotransferase level (14% vs 11%).

Veno-occlusive liver disease occurred in 11% of patients in the inotuzumab arm and 1% in the chemotherapy arm.

There were 17 deaths during treatment in the inotuzumab arm and 11 in the chemotherapy arm. Four deaths were considered related to inotuzumab, and 2 were thought to be related to chemotherapy.

Photo by Bill Branson

The US Food and Drug Administration (FDA) has approved inotuzumab ozogamicin (Besponsa®) for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

The labeling for inotuzumab ozogamicin includes a boxed warning stating that the drug poses a risk of hepatotoxicity, including hepatic veno-occlusive disease (or sinusoidal obstruction syndrome), as well as an increased risk of post-transplant non-relapse mortality.

The full prescribing information for inotuzumab ozogamicin is available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761040s000lbl.pdf.

Inotuzumab ozogamicin is an antibody-drug conjugate that consists of a monoclonal antibody targeting CD22 and a cytotoxic agent known as calicheamicin.

The product originates from a collaboration between Pfizer and Celltech (now UCB), but Pfizer has sole responsibility for all manufacturing and clinical development activities.

Inotuzumab ozogamicin was reviewed and approved under the FDA’s breakthrough therapy designation and priority review programs.

The application for inotuzumab ozogamicin was supported by results from the phase 3 INO-VATE trial, which were published in NEJM in June 2016.

The trial enrolled 326 adults with relapsed or refractory B-cell ALL. Patients received inotuzumab ozogamicin or 1 of 3 chemotherapy regimens (high-dose cytarabine, cytarabine plus mitoxantrone, or fludarabine, cytarabine, and granulocyte colony-stimulating factor).

The rate of complete remission, including incomplete hematologic recovery, was 80.7% in the inotuzumab arm and 29.4% in the chemotherapy arm (P<0.001). The median duration of remission was 4.6 months and 3.1 months, respectively (P=0.03).

Forty-one percent of patients treated with inotuzumab and 11% of those who received chemotherapy proceeded to stem cell transplant directly after treatment (P<0.001).

The median progression-free survival was 5.0 months in the inotuzumab arm and 1.8 months in the chemotherapy arm (P<0.001).

The median overall survival was 7.7 months and 6.7 months, respectively (P=0.04). This did not meet the prespecified boundary of significance (P=0.0208).

Liver-related adverse events were more common in the inotuzumab arm than the chemotherapy arm. The most frequent of these were increased aspartate aminotransferase level (20% vs 10%), hyperbilirubinemia (15% vs 10%), and increased alanine aminotransferase level (14% vs 11%).

Veno-occlusive liver disease occurred in 11% of patients in the inotuzumab arm and 1% in the chemotherapy arm.

There were 17 deaths during treatment in the inotuzumab arm and 11 in the chemotherapy arm. Four deaths were considered related to inotuzumab, and 2 were thought to be related to chemotherapy.

Photo by Bill Branson

The US Food and Drug Administration (FDA) has approved inotuzumab ozogamicin (Besponsa®) for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

The labeling for inotuzumab ozogamicin includes a boxed warning stating that the drug poses a risk of hepatotoxicity, including hepatic veno-occlusive disease (or sinusoidal obstruction syndrome), as well as an increased risk of post-transplant non-relapse mortality.

The full prescribing information for inotuzumab ozogamicin is available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761040s000lbl.pdf.

Inotuzumab ozogamicin is an antibody-drug conjugate that consists of a monoclonal antibody targeting CD22 and a cytotoxic agent known as calicheamicin.

The product originates from a collaboration between Pfizer and Celltech (now UCB), but Pfizer has sole responsibility for all manufacturing and clinical development activities.

Inotuzumab ozogamicin was reviewed and approved under the FDA’s breakthrough therapy designation and priority review programs.

The application for inotuzumab ozogamicin was supported by results from the phase 3 INO-VATE trial, which were published in NEJM in June 2016.

The trial enrolled 326 adults with relapsed or refractory B-cell ALL. Patients received inotuzumab ozogamicin or 1 of 3 chemotherapy regimens (high-dose cytarabine, cytarabine plus mitoxantrone, or fludarabine, cytarabine, and granulocyte colony-stimulating factor).

The rate of complete remission, including incomplete hematologic recovery, was 80.7% in the inotuzumab arm and 29.4% in the chemotherapy arm (P<0.001). The median duration of remission was 4.6 months and 3.1 months, respectively (P=0.03).

Forty-one percent of patients treated with inotuzumab and 11% of those who received chemotherapy proceeded to stem cell transplant directly after treatment (P<0.001).

The median progression-free survival was 5.0 months in the inotuzumab arm and 1.8 months in the chemotherapy arm (P<0.001).

The median overall survival was 7.7 months and 6.7 months, respectively (P=0.04). This did not meet the prespecified boundary of significance (P=0.0208).

Liver-related adverse events were more common in the inotuzumab arm than the chemotherapy arm. The most frequent of these were increased aspartate aminotransferase level (20% vs 10%), hyperbilirubinemia (15% vs 10%), and increased alanine aminotransferase level (14% vs 11%).

Veno-occlusive liver disease occurred in 11% of patients in the inotuzumab arm and 1% in the chemotherapy arm.

There were 17 deaths during treatment in the inotuzumab arm and 11 in the chemotherapy arm. Four deaths were considered related to inotuzumab, and 2 were thought to be related to chemotherapy.

Photo by Darren Baker

A new study indicates that survivors of the Holocaust have experienced a small but consistent increase in the risk of developing cancer.

The findings, published in the journal Cancer, offer an example of how extreme population-level tragedies can have an impact on health.

Holocaust survivors were exposed to a variety of factors that have been linked with cancer.

So researchers set out to investigate whether the starvation, overcrowding, infectious diseases, and psychological stress that survivors endured might have contributed to the development of cancer in some individuals.

The team studied 152,622 Holocaust survivors who were followed for more than 45 years.

The researchers used 2 definitions of exposure to classify the survivors.

One definition was based on an individual’s entitlement for compensation for suffering persecution during the war. The other was based on the country of origin, dividing countries into those that were directly governed by Nazi Germany and those that were not occupied by Nazis.

The cancer incidence was significantly higher in survivors who were granted compensation than in those who were not—21.9% and 16.1%, respectively (P<0.0001).

However, the difference between survivors from occupied and non-occupied countries was not significant—22.7% and 21.4%, respectively.

On the other hand, when the researchers adjusted for confounding factors, survivors who had been exposed by either definition had a significantly increased risk of cancer.

For survivors who were granted compensation, the hazard ratio (HR) was 1.06 (P<0.001). For survivors born in occupied countries, the HR was 1.08 (P<0.001).

There was no increased risk of acute or chronic leukemia among patients who received compensation. And there was no increased risk of acute leukemia for survivors born in occupied countries.

However, there was a significantly increased risk of chronic leukemia among survivors born in occupied countries (HR=1.33, P=0.001)

“The data emphasize the importance of learning about the combined effect of several exposures occurring intensely and contemporaneously on cancer risk, such as those that unfortunately occurred during World War II,” said study author Siegal Sadetzki, MD, of the Chaim Sheba Medical Center in Tel HaShomer, Israel.

An editorial related to this study noted that the association between cancer and the extreme deprivation experienced by Holocaust survivors may also have parallels with other extreme population-level events, including in racial/ethnic minority groups experiencing severe social deprivation over time.

Photo by Darren Baker

A new study indicates that survivors of the Holocaust have experienced a small but consistent increase in the risk of developing cancer.

The findings, published in the journal Cancer, offer an example of how extreme population-level tragedies can have an impact on health.

Holocaust survivors were exposed to a variety of factors that have been linked with cancer.

So researchers set out to investigate whether the starvation, overcrowding, infectious diseases, and psychological stress that survivors endured might have contributed to the development of cancer in some individuals.

The team studied 152,622 Holocaust survivors who were followed for more than 45 years.

The researchers used 2 definitions of exposure to classify the survivors.

One definition was based on an individual’s entitlement for compensation for suffering persecution during the war. The other was based on the country of origin, dividing countries into those that were directly governed by Nazi Germany and those that were not occupied by Nazis.

The cancer incidence was significantly higher in survivors who were granted compensation than in those who were not—21.9% and 16.1%, respectively (P<0.0001).

However, the difference between survivors from occupied and non-occupied countries was not significant—22.7% and 21.4%, respectively.

On the other hand, when the researchers adjusted for confounding factors, survivors who had been exposed by either definition had a significantly increased risk of cancer.

For survivors who were granted compensation, the hazard ratio (HR) was 1.06 (P<0.001). For survivors born in occupied countries, the HR was 1.08 (P<0.001).

There was no increased risk of acute or chronic leukemia among patients who received compensation. And there was no increased risk of acute leukemia for survivors born in occupied countries.

However, there was a significantly increased risk of chronic leukemia among survivors born in occupied countries (HR=1.33, P=0.001)

“The data emphasize the importance of learning about the combined effect of several exposures occurring intensely and contemporaneously on cancer risk, such as those that unfortunately occurred during World War II,” said study author Siegal Sadetzki, MD, of the Chaim Sheba Medical Center in Tel HaShomer, Israel.

An editorial related to this study noted that the association between cancer and the extreme deprivation experienced by Holocaust survivors may also have parallels with other extreme population-level events, including in racial/ethnic minority groups experiencing severe social deprivation over time.

Photo by Darren Baker

A new study indicates that survivors of the Holocaust have experienced a small but consistent increase in the risk of developing cancer.

The findings, published in the journal Cancer, offer an example of how extreme population-level tragedies can have an impact on health.

Holocaust survivors were exposed to a variety of factors that have been linked with cancer.

So researchers set out to investigate whether the starvation, overcrowding, infectious diseases, and psychological stress that survivors endured might have contributed to the development of cancer in some individuals.

The team studied 152,622 Holocaust survivors who were followed for more than 45 years.

The researchers used 2 definitions of exposure to classify the survivors.

One definition was based on an individual’s entitlement for compensation for suffering persecution during the war. The other was based on the country of origin, dividing countries into those that were directly governed by Nazi Germany and those that were not occupied by Nazis.

The cancer incidence was significantly higher in survivors who were granted compensation than in those who were not—21.9% and 16.1%, respectively (P<0.0001).

However, the difference between survivors from occupied and non-occupied countries was not significant—22.7% and 21.4%, respectively.

On the other hand, when the researchers adjusted for confounding factors, survivors who had been exposed by either definition had a significantly increased risk of cancer.

For survivors who were granted compensation, the hazard ratio (HR) was 1.06 (P<0.001). For survivors born in occupied countries, the HR was 1.08 (P<0.001).

There was no increased risk of acute or chronic leukemia among patients who received compensation. And there was no increased risk of acute leukemia for survivors born in occupied countries.

However, there was a significantly increased risk of chronic leukemia among survivors born in occupied countries (HR=1.33, P=0.001)

“The data emphasize the importance of learning about the combined effect of several exposures occurring intensely and contemporaneously on cancer risk, such as those that unfortunately occurred during World War II,” said study author Siegal Sadetzki, MD, of the Chaim Sheba Medical Center in Tel HaShomer, Israel.

An editorial related to this study noted that the association between cancer and the extreme deprivation experienced by Holocaust survivors may also have parallels with other extreme population-level events, including in racial/ethnic minority groups experiencing severe social deprivation over time.

Photo by Juan D. Alfonso

The US Food and Drug Administration (FDA) has made available a panel of human plasma samples that can be used to evaluate serological tests for detecting Zika virus infection.

The panel consists of plasma samples from anonymous individuals infected with Zika, West Nile, or dengue viruses.

Diagnostic developers can use the panel to assess whether their tests can help distinguish recent Zika virus infection from infection with West Nile or dengue.

The panel is available to developers who have interacted with the FDA and are seeking Emergency Use Authorization (EUA) for devices that are in the final stages of validation.

Other developers interested in requesting a panel may contact the FDA at [email protected].

The agency said the panel can also be used to compare the performance of Zika virus tests that are already available under an EUA.

To date, the FDA has granted EUAs to 3 serological tests for detection of recent Zika virus infection: Zika MAC-ELISA, ZIKV Detect IgM Capture ELISA, and LIAISON XL Zika Capture IgM Assay.

“At the onset of the Zika virus outbreak, when little was known about the disease or how to diagnose it, the FDA worked quickly with manufacturers to encourage the development of diagnostic tests and ensure they were available using its Emergency Use Authorization authorities,” said FDA Commissioner Scott Gottlieb, MD.

“By providing manufacturers of these tests with standardized patient samples to use in properly validating these diagnostics, we will be able to better assess how well their tests perform. This is part of our effort to ultimately bring these tests through the FDA’s formal review process to better ensure their reliability, and to enable broader access to Zika diagnostic testing.”

The FDA panel was prepared using samples from Zika virus-infected individuals provided by Blood Systems Research Institute. The samples from individuals infected with dengue and West Nile virus were obtained separately.

Photo by Juan D. Alfonso

The US Food and Drug Administration (FDA) has made available a panel of human plasma samples that can be used to evaluate serological tests for detecting Zika virus infection.

The panel consists of plasma samples from anonymous individuals infected with Zika, West Nile, or dengue viruses.

Diagnostic developers can use the panel to assess whether their tests can help distinguish recent Zika virus infection from infection with West Nile or dengue.

The panel is available to developers who have interacted with the FDA and are seeking Emergency Use Authorization (EUA) for devices that are in the final stages of validation.

Other developers interested in requesting a panel may contact the FDA at [email protected].

The agency said the panel can also be used to compare the performance of Zika virus tests that are already available under an EUA.

To date, the FDA has granted EUAs to 3 serological tests for detection of recent Zika virus infection: Zika MAC-ELISA, ZIKV Detect IgM Capture ELISA, and LIAISON XL Zika Capture IgM Assay.

“At the onset of the Zika virus outbreak, when little was known about the disease or how to diagnose it, the FDA worked quickly with manufacturers to encourage the development of diagnostic tests and ensure they were available using its Emergency Use Authorization authorities,” said FDA Commissioner Scott Gottlieb, MD.

“By providing manufacturers of these tests with standardized patient samples to use in properly validating these diagnostics, we will be able to better assess how well their tests perform. This is part of our effort to ultimately bring these tests through the FDA’s formal review process to better ensure their reliability, and to enable broader access to Zika diagnostic testing.”

The FDA panel was prepared using samples from Zika virus-infected individuals provided by Blood Systems Research Institute. The samples from individuals infected with dengue and West Nile virus were obtained separately.

Photo by Juan D. Alfonso

The US Food and Drug Administration (FDA) has made available a panel of human plasma samples that can be used to evaluate serological tests for detecting Zika virus infection.

The panel consists of plasma samples from anonymous individuals infected with Zika, West Nile, or dengue viruses.

Diagnostic developers can use the panel to assess whether their tests can help distinguish recent Zika virus infection from infection with West Nile or dengue.

The panel is available to developers who have interacted with the FDA and are seeking Emergency Use Authorization (EUA) for devices that are in the final stages of validation.

Other developers interested in requesting a panel may contact the FDA at [email protected].

The agency said the panel can also be used to compare the performance of Zika virus tests that are already available under an EUA.

To date, the FDA has granted EUAs to 3 serological tests for detection of recent Zika virus infection: Zika MAC-ELISA, ZIKV Detect IgM Capture ELISA, and LIAISON XL Zika Capture IgM Assay.

“At the onset of the Zika virus outbreak, when little was known about the disease or how to diagnose it, the FDA worked quickly with manufacturers to encourage the development of diagnostic tests and ensure they were available using its Emergency Use Authorization authorities,” said FDA Commissioner Scott Gottlieb, MD.

“By providing manufacturers of these tests with standardized patient samples to use in properly validating these diagnostics, we will be able to better assess how well their tests perform. This is part of our effort to ultimately bring these tests through the FDA’s formal review process to better ensure their reliability, and to enable broader access to Zika diagnostic testing.”

The FDA panel was prepared using samples from Zika virus-infected individuals provided by Blood Systems Research Institute. The samples from individuals infected with dengue and West Nile virus were obtained separately.

The use of oral contraceptives may be associated with a reduced risk of rheumatoid arthritis based on findings from a large, population-based, case-control study in Sweden.

The lowered risk for rheumatoid arthritis in the study conducted by Cecilia Orellana, PhD, of the Institute of Environmental Medicine at the Karolinska Institute, Stockholm, and her coauthors applied only to patients who tested positive for anticitrullinated protein antibodies (ACPA) and to those who used oral contraceptives for 7 or more years. The investigators also found a significant reduction in RA risk for women who breastfed their children.

areeya_ann/Thinkstock

The use of oral contraceptives may be associated with a reduced risk of rheumatoid arthritis based on findings from a large, population-based, case-control study in Sweden.

The lowered risk for rheumatoid arthritis in the study conducted by Cecilia Orellana, PhD, of the Institute of Environmental Medicine at the Karolinska Institute, Stockholm, and her coauthors applied only to patients who tested positive for anticitrullinated protein antibodies (ACPA) and to those who used oral contraceptives for 7 or more years. The investigators also found a significant reduction in RA risk for women who breastfed their children.

areeya_ann/Thinkstock

The use of oral contraceptives may be associated with a reduced risk of rheumatoid arthritis based on findings from a large, population-based, case-control study in Sweden.

The lowered risk for rheumatoid arthritis in the study conducted by Cecilia Orellana, PhD, of the Institute of Environmental Medicine at the Karolinska Institute, Stockholm, and her coauthors applied only to patients who tested positive for anticitrullinated protein antibodies (ACPA) and to those who used oral contraceptives for 7 or more years. The investigators also found a significant reduction in RA risk for women who breastfed their children.

areeya_ann/Thinkstock

The sinus of Valsalva segment can be preserved during aortic valve replacement irrespective of the type of valve pathology, according to a recent study by Rita Karianna Milewski, MD, and her colleagues at the Hospital of the University of Pennsylvania, Philadelphia.

Severe aortic root dilation coupled to aortic valve disease requires root replacement in patients with a tricuspid or bicuspid aortic valve. Commonly, an aortic valve replacement and supracoronary ascending aorta replacement (AVRSCAAR) procedure has been used for patients who have a mild to moderately dilated sinus segment. One advantage of the procedure is that it retains the sinus of Valsalva (SOV) and preserves the intact coronary ostia.

However, the long-term behavior and risk of aortic events for the retained SOV in both BAV and TAV patients remains unclear, according to Dr. Milewski and her colleagues.

Previous researchers have suggested that patients with BAV and TAV have different rates of complications of the remaining aorta and dilation of the proximal aorta and retained sinus segment. In addition, it has been suggested that the cause of aortic dilation is different in patients with aortic stenosis (AS) and aortic insufficiency (AI) and is based on TAV and BAV morphology, histology, and hemodynamic flow patterns.

However, in the August issue of the Journal of Thoracic and Cardiovascular Surgery, Dr. Milewski and her colleagues reported on their study showing that, in patients with nonaneurysmal SOV undergoing AVRSCAAR, the sinus of Valsalva segment can be preserved regardless of the type of valvular pathology (aortic stenosis vs. aortic insufficiency) or valvular morphology (BAV vs. TAV).

The researchers retrospectively reviewed a prospectively maintained institutional database to stratify all patients by BAV or TAV valvular pathology with concomitant ascending aortic aneurysm who underwent an elective AVRSCAAR from 2002 to 2015 (J Thorac Cardiovasc Surg. 2017;154:421-32).

The distribution of the 428 patients meeting inclusion criteria by subgroups was: BAV group (254 patients: BAV-AS = 178; BAV-AI = 76); TAV group (174 patients: TAV-AS = 61; TAV-AI =113). Preoperative sinus of Valsalva dimensions were divided into 3 subgroups (less than 40 mm, 40-45 mm, and greater than 45 mm).

The mean patient age for patients with BAV and TAV was 59 years and 72 years (P less than .001), respectively (with 78% with BAV being men and 57% with TAV being men). There was a significantly higher subpopulation of AS in the BAV cohort vs. TAV-AS (70% vs. 35%; P less than .001).

With regard to SOV sizing, there was no significant difference in mean preoperative aortic root diameters between BAV and TAV cohorts for the AS or AI subpopulations.

In-hospital/30-day mortality was significantly higher in patients with TAV (5.2%) than in patients with BAV (1.6%, P = .033). In addition, the incidence of transient ischemic attack/stroke was significantly higher in the TAV group (3.4%) vs. the BAV group (0.8%, P = .04).

Valvular morphology and pathology at baseline, preoperative SOV diameter, postoperative time course, and interaction effect of preoperative SOV diameters and postoperative time course were used as covariates to assess outcomes. Within-subject and within–stratified subgroup comparison failed to show main effects across the follow-up times on postoperative SOV size patterns (P = .935), implying that the SOV trends were stable and sustained (discharge to greater than or equal to 10 years) irrespective of valvular morphology and pathology (BAV-AI, BAV-AS, TAV-AI, and TAV-AS).

Preoperative SOV dimensions significantly affected the retained postoperative sinus dimensions (P less than .001), according to Dr. Milewski and her colleagues.

The data indicated that an initial and pronounced postoperative decrease in SOV dimensions occurs with AVRSCAAR independently of aortic valve morphology, aortic valve pathology, and age, they added.

The 10-year freedom from aortic reoperation rates were 97% and 95% in the BAV and TAV subgroups, respectively. The BAV group had significantly improved reoperation-free survival, compared with the TAV group (P less than .001), while the type of valvular pathology within each group did not show a significant survival difference.

“Irrespective of the aortic valve morphology or valve pathology, in patients with mild to moderate aortic root dilatation (less than 45 mm), preservation of the SOV segment in the context of an AVRSCAAR procedure is justified. Continued further follow-up will be important to understand the long-term outcomes of sinus preservation, especially in the younger population with BAVs,” the researchers concluded.

The authors reported having no financial conflicts to disclose.

[email protected]

The sinus of Valsalva segment can be preserved during aortic valve replacement irrespective of the type of valve pathology, according to a recent study by Rita Karianna Milewski, MD, and her colleagues at the Hospital of the University of Pennsylvania, Philadelphia.

Severe aortic root dilation coupled to aortic valve disease requires root replacement in patients with a tricuspid or bicuspid aortic valve. Commonly, an aortic valve replacement and supracoronary ascending aorta replacement (AVRSCAAR) procedure has been used for patients who have a mild to moderately dilated sinus segment. One advantage of the procedure is that it retains the sinus of Valsalva (SOV) and preserves the intact coronary ostia.

However, the long-term behavior and risk of aortic events for the retained SOV in both BAV and TAV patients remains unclear, according to Dr. Milewski and her colleagues.

Previous researchers have suggested that patients with BAV and TAV have different rates of complications of the remaining aorta and dilation of the proximal aorta and retained sinus segment. In addition, it has been suggested that the cause of aortic dilation is different in patients with aortic stenosis (AS) and aortic insufficiency (AI) and is based on TAV and BAV morphology, histology, and hemodynamic flow patterns.

However, in the August issue of the Journal of Thoracic and Cardiovascular Surgery, Dr. Milewski and her colleagues reported on their study showing that, in patients with nonaneurysmal SOV undergoing AVRSCAAR, the sinus of Valsalva segment can be preserved regardless of the type of valvular pathology (aortic stenosis vs. aortic insufficiency) or valvular morphology (BAV vs. TAV).

The researchers retrospectively reviewed a prospectively maintained institutional database to stratify all patients by BAV or TAV valvular pathology with concomitant ascending aortic aneurysm who underwent an elective AVRSCAAR from 2002 to 2015 (J Thorac Cardiovasc Surg. 2017;154:421-32).

The distribution of the 428 patients meeting inclusion criteria by subgroups was: BAV group (254 patients: BAV-AS = 178; BAV-AI = 76); TAV group (174 patients: TAV-AS = 61; TAV-AI =113). Preoperative sinus of Valsalva dimensions were divided into 3 subgroups (less than 40 mm, 40-45 mm, and greater than 45 mm).

The mean patient age for patients with BAV and TAV was 59 years and 72 years (P less than .001), respectively (with 78% with BAV being men and 57% with TAV being men). There was a significantly higher subpopulation of AS in the BAV cohort vs. TAV-AS (70% vs. 35%; P less than .001).

With regard to SOV sizing, there was no significant difference in mean preoperative aortic root diameters between BAV and TAV cohorts for the AS or AI subpopulations.

In-hospital/30-day mortality was significantly higher in patients with TAV (5.2%) than in patients with BAV (1.6%, P = .033). In addition, the incidence of transient ischemic attack/stroke was significantly higher in the TAV group (3.4%) vs. the BAV group (0.8%, P = .04).

Valvular morphology and pathology at baseline, preoperative SOV diameter, postoperative time course, and interaction effect of preoperative SOV diameters and postoperative time course were used as covariates to assess outcomes. Within-subject and within–stratified subgroup comparison failed to show main effects across the follow-up times on postoperative SOV size patterns (P = .935), implying that the SOV trends were stable and sustained (discharge to greater than or equal to 10 years) irrespective of valvular morphology and pathology (BAV-AI, BAV-AS, TAV-AI, and TAV-AS).

Preoperative SOV dimensions significantly affected the retained postoperative sinus dimensions (P less than .001), according to Dr. Milewski and her colleagues.

The data indicated that an initial and pronounced postoperative decrease in SOV dimensions occurs with AVRSCAAR independently of aortic valve morphology, aortic valve pathology, and age, they added.

The 10-year freedom from aortic reoperation rates were 97% and 95% in the BAV and TAV subgroups, respectively. The BAV group had significantly improved reoperation-free survival, compared with the TAV group (P less than .001), while the type of valvular pathology within each group did not show a significant survival difference.

“Irrespective of the aortic valve morphology or valve pathology, in patients with mild to moderate aortic root dilatation (less than 45 mm), preservation of the SOV segment in the context of an AVRSCAAR procedure is justified. Continued further follow-up will be important to understand the long-term outcomes of sinus preservation, especially in the younger population with BAVs,” the researchers concluded.

The authors reported having no financial conflicts to disclose.

[email protected]

The sinus of Valsalva segment can be preserved during aortic valve replacement irrespective of the type of valve pathology, according to a recent study by Rita Karianna Milewski, MD, and her colleagues at the Hospital of the University of Pennsylvania, Philadelphia.

Severe aortic root dilation coupled to aortic valve disease requires root replacement in patients with a tricuspid or bicuspid aortic valve. Commonly, an aortic valve replacement and supracoronary ascending aorta replacement (AVRSCAAR) procedure has been used for patients who have a mild to moderately dilated sinus segment. One advantage of the procedure is that it retains the sinus of Valsalva (SOV) and preserves the intact coronary ostia.

However, the long-term behavior and risk of aortic events for the retained SOV in both BAV and TAV patients remains unclear, according to Dr. Milewski and her colleagues.

Previous researchers have suggested that patients with BAV and TAV have different rates of complications of the remaining aorta and dilation of the proximal aorta and retained sinus segment. In addition, it has been suggested that the cause of aortic dilation is different in patients with aortic stenosis (AS) and aortic insufficiency (AI) and is based on TAV and BAV morphology, histology, and hemodynamic flow patterns.

However, in the August issue of the Journal of Thoracic and Cardiovascular Surgery, Dr. Milewski and her colleagues reported on their study showing that, in patients with nonaneurysmal SOV undergoing AVRSCAAR, the sinus of Valsalva segment can be preserved regardless of the type of valvular pathology (aortic stenosis vs. aortic insufficiency) or valvular morphology (BAV vs. TAV).

The researchers retrospectively reviewed a prospectively maintained institutional database to stratify all patients by BAV or TAV valvular pathology with concomitant ascending aortic aneurysm who underwent an elective AVRSCAAR from 2002 to 2015 (J Thorac Cardiovasc Surg. 2017;154:421-32).

The distribution of the 428 patients meeting inclusion criteria by subgroups was: BAV group (254 patients: BAV-AS = 178; BAV-AI = 76); TAV group (174 patients: TAV-AS = 61; TAV-AI =113). Preoperative sinus of Valsalva dimensions were divided into 3 subgroups (less than 40 mm, 40-45 mm, and greater than 45 mm).

The mean patient age for patients with BAV and TAV was 59 years and 72 years (P less than .001), respectively (with 78% with BAV being men and 57% with TAV being men). There was a significantly higher subpopulation of AS in the BAV cohort vs. TAV-AS (70% vs. 35%; P less than .001).

With regard to SOV sizing, there was no significant difference in mean preoperative aortic root diameters between BAV and TAV cohorts for the AS or AI subpopulations.

In-hospital/30-day mortality was significantly higher in patients with TAV (5.2%) than in patients with BAV (1.6%, P = .033). In addition, the incidence of transient ischemic attack/stroke was significantly higher in the TAV group (3.4%) vs. the BAV group (0.8%, P = .04).

Valvular morphology and pathology at baseline, preoperative SOV diameter, postoperative time course, and interaction effect of preoperative SOV diameters and postoperative time course were used as covariates to assess outcomes. Within-subject and within–stratified subgroup comparison failed to show main effects across the follow-up times on postoperative SOV size patterns (P = .935), implying that the SOV trends were stable and sustained (discharge to greater than or equal to 10 years) irrespective of valvular morphology and pathology (BAV-AI, BAV-AS, TAV-AI, and TAV-AS).

Preoperative SOV dimensions significantly affected the retained postoperative sinus dimensions (P less than .001), according to Dr. Milewski and her colleagues.

The data indicated that an initial and pronounced postoperative decrease in SOV dimensions occurs with AVRSCAAR independently of aortic valve morphology, aortic valve pathology, and age, they added.

The 10-year freedom from aortic reoperation rates were 97% and 95% in the BAV and TAV subgroups, respectively. The BAV group had significantly improved reoperation-free survival, compared with the TAV group (P less than .001), while the type of valvular pathology within each group did not show a significant survival difference.

“Irrespective of the aortic valve morphology or valve pathology, in patients with mild to moderate aortic root dilatation (less than 45 mm), preservation of the SOV segment in the context of an AVRSCAAR procedure is justified. Continued further follow-up will be important to understand the long-term outcomes of sinus preservation, especially in the younger population with BAVs,” the researchers concluded.

The authors reported having no financial conflicts to disclose.

[email protected]

Obinutuzumab with CHOP therapy did not improve progression-free survival, compared with rituximab plus CHOP, in patients with previously untreated diffuse large B-cell lymphoma (DLBCL), according to results from a phase 3 trial published in the Journal of Clinical Oncology. (2017 Aug 10. doi: 10.1200/JCO.2017.73.3402)

The findings suggest that obinutuzumab, a glycoengineered, type II, anti-CD20 monoclonal antibody, might not offer a benefit over standard treatment with rituximab, an anti-CD20 monoclonal antibody, when used with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone).

A total of 1,418 patients were enrolled at 207 centers in 29 countries in the GOYA trial and were randomly assigned to one regimen or the other. The mean duration of exposure to the drugs was 25 weeks for both. The progression-free survival was 69.6% for obinutuzumab-CHOP – also known as G-CHOP – and 66.9% for rituximab-CHOP, not a statistically significant difference, wrote Umberto Vitolo, MD, of University-Hospital Città della Salute e della Scienza, Torino, Italy, and his fellow investigators.

The rate of adverse events was similar between the two groups. The lack of superiority of obinutuzumab comes after findings of its superiority in untreated follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL). The investigators suggested that this may be a sign that obinutuzumab’s efficacy is best seen in less aggressive disease types.

“Given the advantages of G-based therapy in patients with FL and CLL, the lack of benefit of G-CHOP in patients with DLBCL in the GOYA study was unexpected, and the reasons for it are unclear,” they wrote. “This lack of benefit might simply have resulted from the differences in biologic and clinical profiles between indolent lymphoproliferative diseases, such as FL and CLL, and aggressive ones, such as DLBCL.”

The study was sponsored by F. Hoffman-La Roche, the manufacturer of the two drugs, and had support from Fondazione Italiana Linfomi.

Obinutuzumab with CHOP therapy did not improve progression-free survival, compared with rituximab plus CHOP, in patients with previously untreated diffuse large B-cell lymphoma (DLBCL), according to results from a phase 3 trial published in the Journal of Clinical Oncology. (2017 Aug 10. doi: 10.1200/JCO.2017.73.3402)

The findings suggest that obinutuzumab, a glycoengineered, type II, anti-CD20 monoclonal antibody, might not offer a benefit over standard treatment with rituximab, an anti-CD20 monoclonal antibody, when used with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone).

A total of 1,418 patients were enrolled at 207 centers in 29 countries in the GOYA trial and were randomly assigned to one regimen or the other. The mean duration of exposure to the drugs was 25 weeks for both. The progression-free survival was 69.6% for obinutuzumab-CHOP – also known as G-CHOP – and 66.9% for rituximab-CHOP, not a statistically significant difference, wrote Umberto Vitolo, MD, of University-Hospital Città della Salute e della Scienza, Torino, Italy, and his fellow investigators.

The rate of adverse events was similar between the two groups. The lack of superiority of obinutuzumab comes after findings of its superiority in untreated follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL). The investigators suggested that this may be a sign that obinutuzumab’s efficacy is best seen in less aggressive disease types.

“Given the advantages of G-based therapy in patients with FL and CLL, the lack of benefit of G-CHOP in patients with DLBCL in the GOYA study was unexpected, and the reasons for it are unclear,” they wrote. “This lack of benefit might simply have resulted from the differences in biologic and clinical profiles between indolent lymphoproliferative diseases, such as FL and CLL, and aggressive ones, such as DLBCL.”

The study was sponsored by F. Hoffman-La Roche, the manufacturer of the two drugs, and had support from Fondazione Italiana Linfomi.

Obinutuzumab with CHOP therapy did not improve progression-free survival, compared with rituximab plus CHOP, in patients with previously untreated diffuse large B-cell lymphoma (DLBCL), according to results from a phase 3 trial published in the Journal of Clinical Oncology. (2017 Aug 10. doi: 10.1200/JCO.2017.73.3402)

The findings suggest that obinutuzumab, a glycoengineered, type II, anti-CD20 monoclonal antibody, might not offer a benefit over standard treatment with rituximab, an anti-CD20 monoclonal antibody, when used with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone).

A total of 1,418 patients were enrolled at 207 centers in 29 countries in the GOYA trial and were randomly assigned to one regimen or the other. The mean duration of exposure to the drugs was 25 weeks for both. The progression-free survival was 69.6% for obinutuzumab-CHOP – also known as G-CHOP – and 66.9% for rituximab-CHOP, not a statistically significant difference, wrote Umberto Vitolo, MD, of University-Hospital Città della Salute e della Scienza, Torino, Italy, and his fellow investigators.

The rate of adverse events was similar between the two groups. The lack of superiority of obinutuzumab comes after findings of its superiority in untreated follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL). The investigators suggested that this may be a sign that obinutuzumab’s efficacy is best seen in less aggressive disease types.

“Given the advantages of G-based therapy in patients with FL and CLL, the lack of benefit of G-CHOP in patients with DLBCL in the GOYA study was unexpected, and the reasons for it are unclear,” they wrote. “This lack of benefit might simply have resulted from the differences in biologic and clinical profiles between indolent lymphoproliferative diseases, such as FL and CLL, and aggressive ones, such as DLBCL.”

The study was sponsored by F. Hoffman-La Roche, the manufacturer of the two drugs, and had support from Fondazione Italiana Linfomi.

The Food and Drug Administration has approved the antibody drug conjugate inotuzumab ozogamicin for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

The treatment, to be marketed by Pfizer as Besponsa, won approval based on the results of the INO-VATE ALL trial, which randomized 326 patients to receive either inotuzumab ozogamicin (164 patients) or a chemotherapy regimen of the investigator’s choice (162 patients). To be considered for inclusion in the trial, patients with Philadelphia chromosome–negative or –positive relapsed or refractory B-cell precursor ALL were required to have at least 5% bone marrow blasts and have received one or two induction chemotherapy regimens.

[email protected]

On Twitter @denisefulton

The Food and Drug Administration has approved the antibody drug conjugate inotuzumab ozogamicin for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

The treatment, to be marketed by Pfizer as Besponsa, won approval based on the results of the INO-VATE ALL trial, which randomized 326 patients to receive either inotuzumab ozogamicin (164 patients) or a chemotherapy regimen of the investigator’s choice (162 patients). To be considered for inclusion in the trial, patients with Philadelphia chromosome–negative or –positive relapsed or refractory B-cell precursor ALL were required to have at least 5% bone marrow blasts and have received one or two induction chemotherapy regimens.

[email protected]

On Twitter @denisefulton

The Food and Drug Administration has approved the antibody drug conjugate inotuzumab ozogamicin for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

The treatment, to be marketed by Pfizer as Besponsa, won approval based on the results of the INO-VATE ALL trial, which randomized 326 patients to receive either inotuzumab ozogamicin (164 patients) or a chemotherapy regimen of the investigator’s choice (162 patients). To be considered for inclusion in the trial, patients with Philadelphia chromosome–negative or –positive relapsed or refractory B-cell precursor ALL were required to have at least 5% bone marrow blasts and have received one or two induction chemotherapy regimens.

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