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April 2012
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IDSA Journal Club
April 2012

In this feature, a panel of IDSA members identifies and critiques important new studies in the current literature that have a significant impact on the practice of infectious diseases medicine.

Click here for the previous edition of Journal Club. For a review of other recent research in the infectious diseases literature, see “In the Literature,” by Stanley Deresinski, MD, in each issue of Clinical Infectious Diseases.

The WISCA: Flipping the Traditional Antibiogram on its Head
Reviewed by Christopher J. Graber, MD, MPH

An article published in the April 2012 issue of Infection Control and Hospital Epidemiology describes a novel approach in using facility antimicrobial resistance data to provide decision support for empiric antimicrobial prescription. Most facilities typically publish an antibiogram that reports antimicrobial resistance according to organism. However, the infecting organism is typically not known at the time when empiric antimicrobial therapy is prescribed, limiting the antibiogram’s usefulness.

The authors describe a method of reporting antimicrobial resistance according to presenting clinical syndrome, which they call the “Weighted-Incidence Syndromic Combination Antibiogram (WISCA).” It was applied to two clinical syndromes of community onset for which hospitalization was required at their facility from January 2006 to June 2010: urinary tract infection (UTI) and abdominal-biliary tract infection (ABI), identfied by ICD-9 codes and having a relevant positive culture within the first two (for UTI) or four (for ABI) days of admission. For each case, a determination was made based on antimicrobial susceptibility patterns as to whether the infection would have been “covered” by each of a panel of antimicrobial regimens. Results were also stratified according to demographic and clinical factors that may influence antimicrobial resistance, including age, recent emergency department visit or inpatient admission, underlying chronic disease, prior antimicrobial exposure, and prior culture positivity with a multidrug-resistant organism.

Reporting via WISCA yielded valuable information. Though their facility had a fluoroquinolone susceptibility among all E. coli isolates of 84 percent, the authors found that only 62 percent of UTI patients and 37 percent of ABI patients would have had their infections adequately treated with a fluoroquinolone. However, fluoroquinolones were adequate in 82 percent of the UTI patients with no identified risk factors for resistance. Taken together, the WISCA method can serve as a useful template for antimicrobial stewardship teams to assist providers in making individualized decisions regarding empiric antimicrobial therapy.

(Hebert et al. Infect Control Hosp Epidemiol 2012;33(4):381-8.)

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HAART Reduces Risk of TB, But in Some Cases, It’s Too Late
Reviewed by Nina Kim, MD, MSc

Tuberculosis (TB) remains a leading cause of morbidity and mortality in HIV-infected patients worldwide. Multiple studies have shown the benefit of highly active antiretroviral therapy (HAART) in reducing both TB incidence and mortality, but fewer studies have examined how the effect of HAART on TB varies over time and in different patients. One study from the May 1 issue of Clinical Infectious Diseases explored these questions in a large cohort of patients from Western Europe and the United States.

Investigators identified 65,121 HIV-infected adults who were antiretroviral naïve at baseline from 1996 to 2007. They restricted their analysis to patients who did not have an AIDS-defining condition, including a TB diagnosis, during their first month to ensure that events reflected incident rather than prevalent TB. During a median follow-up of 28 months, 712 individuals were diagnosed with TB with an overall incidence of three cases per 1,000 person-years. TB incidence was greatest in patients with CD4 counts <50 cells/mm3 and those older than 50. HAART reduced TB incidence overall by 44 percent, but this reduction was not observed in the high-risk subsets of patients older than 50 or in those with CD4 counts <50 cells/mm3. The risk of TB varied by time from the start of HAART and actually increased by 36 percent within the first three months after HAART initiation, particularly in men, older individuals, and those with lowest baseline CD4 counts. The risk of Pneumocystis pneumonia, in contrast, declined immediately after HAART in this cohort, and remained low even during the first three months.

Increased TB incidence early in HAART has also been reported in another very large cohort from North America and suggests the “unmasking” of TB with HAART-mediated immune reconstitution inflammatory syndrome. These findings underscore the need to improve TB screening and case identification in HIV-infected patients. Clinicians should maintain suspicion for TB even in high-income countries where TB is not endemic, particularly in patients with advanced disease during the first few months of starting HAART.

(HIV-CAUSAL Collaboration, Clin Infect Dis 2012;54(9):1364-72.)

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Perinatal Hepatitis B in the U.S.: Going, but not yet Gone
Reviewed by Christian B. Ramers, MD, MPH

Although hepatitis B incidence in the United States has declined by approximately 82 percent since the introduction of a comprehensive elimination strategy, chronic infections continue to occur, especially among immigrant populations. Chronic infection is much more likely at a younger age of exposure, with perinatally exposed newborns having a rate of 90 percent, compared with just 5 percent in exposed adults. A study in the April 2012 issue of Pediatrics describes substantial progress and a changing epidemiology of perinatal infection following the 1990 launch of the National Perinatal Hepatitis B Prevention Program (PHBPP), which strove to identify hepatitis B surface antigen (HBsAg)-positive mothers and ensure timely prophylaxis and screening of their infants. 

Investigators compiled PHBPP reports from state and local health departments from 1994 to 2008 and reported on estimated births to HBsAg-positive women, the number officially managed by the PHBPP program, and details of the clinical management of exposed infants through follow-up at 12 and 24 months of age. From 1994 to 2008, the estimated number of births to HBsAg-positive women increased from 19,208 to 25,600 (p < 0.001). Over time, a greater proportion of these births were officially managed within the program (40.8 percent to 56.0 percent, p < 0.001). Overall, 94.4 percent of PHBPP-managed infants received both hepatitis B immunoglobulin and hepatitis B vaccine within one day of birth. Surprisingly, vaccination series completion rates decreased from 86.0 percent to 77.7 percent (p = 0.004), but the use of post-vaccination testing increased from 25.1 percent to 56.0 percent (p < 0.001). Perhaps most importantly, the incidence of chronic hepatitis B among tested infants decreased from 2.1 percent in 1999 to 0.8 percent in 2008 (P = 0.001).

This report describes important progress in the identification and effective management of hepatitis B-exposed infants in the United States. Interestingly, the number of births to HBsAg-positive mothers actually increased, suggesting that this situation will continue to be encountered regularly in clinical practice.

(Smith et al. Pediatrics. 2012 April; 129(4):609-616.)

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C. difficile Infections in Hematopoietic Stem Cell Transplant Recipients: Epidemiology and Outcomes
Reviewed by Ed Dominguez, MD

Clostridium difficile infection (CDI) is experiencing a global resurgence due to the hypertoxigenic strain, NAP1. Risk factors include prolonged hospitalization, prolonged antibiotic exposure, and enteric mucosal disruption, all of which are common in hematopoietic stem cell transplant (HSCT) recipients. However, the epidemiology and outcomes in this population are not well understood. The April 15 issue of Clinical Infectious Diseases contains a single-center retrospective case-control study of CDI in HSCT adult recipients.

Between January 2003 and December 2008, 92 CDI cases were seen in 999 HSCT recipients (9.2 percent). The incidence was almost twice as high in allogeneic recipients compared to autologous (12.5 percent vs. 6.5 percent). Furthermore, the median time to infection was later in allogeneic recipients (33 days vs. 6.5 days). To evaluate risk factors, controls were matched 2:1 to each CDI case. Multivariate analysis identified chemotherapy prior to HSCT conditioning; post-transplant high-risk antibiotics; gastrointestinal acute graft-versus-host disease (aGVHD); and vancomycin-resistant enterococcus (VRE) colonization as independent factors for subsequent CDI. Interestingly, receipt of a proton pump inhibitor protected against CDI (adjusted odds ratio, 0.29), contradicting some studies in non-HSCT patients.

The clinical signs of CDI were subdued in HSCT recipients. Only 29.3 percent of patients were febrile, and 2.2 percent had leukocytosis > 20,000 cells/cu mm. All patients were treated with metronidazole or vancomycin, alone or in combination. No recipients had toxic megacolon. All-cause mortality was similar between allogeneic recipients with CDI and allogeneic controls. Recurrence occurred in 21.7 percent of patients a median of 69 days after initial CDI and was strongly associated with subsequent gastrointestinal aGVHD (adjusted odds ratio, 4.23). This sequence of CDI followed by gastrointestinal aGVHD suggests that a proinflammatory cascade may be initiated by the infection. Equipped with these observations, the role of new antibiotics (e.g., fidaxomicin) and modalities (such as fecal microbiota transplant) in HSCT can be evaluated.

(Alonso et al. Clin Infect Dis. 2012;54(8):1053–63.)

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For a review of other recent research in the infectious diseases literature, see “In the Literature,” by Stanley Deresinski, MD, in each issue of Clinical Infectious Diseases:

April 15

  • Mycobacterium abscessus Group: Dealing With Rapidly Growing Mycobacteria Has Become More Complex and Difficult
  • Adenoidectomy Does Not Prevent Recurrent Upper Respiratory Tract Infection

April 1

  • Trimethoprim-Sulfamethoxazole Dose and Methicillin-Resistant Staphylococcus aureus Infections
  • Rifaximin to Prevent Recurrent Diarrhea in Patients With Clostridium difficile Disease Treated With Vancomycin or Metronidazole
  • Oseltamivir Resistance—Does It Quack Like a Duck?

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