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August-September 2013
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IDSA Journal Club
August-September 2013

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.

Health Care- and Community-Acquired P. aeruginosa Infections: Differences and Implications for Outcomes
Reviewed by Zeina Kanafani, MD, MS

Pseudomonas aeruginosa bloodstream infection (BSI) is associated with significant morbidity and mortality. The organism can be multidrug resistant (MDR) and can produce virulence factors such as the type three secretion (TTS) system, which induces destructuration of the cytoskeleton and necrosis of host cells. Although most BSIs due to P. aeruginosa are health care-acquired (HCABSI), the infection can be community-acquired (CABSI). The difference in characteristics, virulence, and outcomes of both types of infections is not fully known; a study recently published in Antimicrobial Agents and Chemotherapy provides some insights.

Researchers conducted a retrospective analysis of 150 cases of documented P. aeruginosa BSI (90 HCABSI and 60 CABSI). Patients in the HCABSI group had higher median Sequential Organ Failure Assessment (SOFA) scores (7 vs. 5; p=0.05), higher likelihood of prior antibiotic therapy (76 percent vs. 40 percent; p<0.001), and longer median length of stay before bacteremia (9 vs. 0 days; p<0.001) compared to patients in the CABSI group. Isolates in the HCABSI arm were more likely to be resistant to ciprofloxacin and ceftazidime than those in the CABSI arm. Eleven isolates were identified as MDR (9 HCABSI; 2 CABSI) and 13 were carbapenem-resistant (12 HCABSI; 1 CABSI). TTS was detected in 99 isolates (61 HCABSI; 38 CABSI).

HCABSI patients had a longer median hospital stay compared to CABSI patients (10 vs. 8 days; p=0.05). However, the 30-day mortality rate was not significantly different between the two groups (36 percent vs. 26 percent; p=0.38). On regression analysis, independent predictors of mortality were TTS phenotype (HR 2.24; 95 percent CI 1.26-4.67) and SOFA score at time of bacteremia (HR 1.18; 95 percent CI 1.10-1.26).

The study findings argue against maintaining a distinct classification of P. aeruginosa HCABSI and CABSI. On the other hand, they highlight the importance of TTS in predicting mortality. The findings suggest future therapies could target TTS in order to improve the outcome of these infections.

(Hattemer et al. Antimicrob Agents Chemother. 2013;57:3969-75.)

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Bail After Negative BAL: Stopping Antibiotics Early After Negative BAL Cultures Not Associated With Increased Mortality
Reviewed by Nirav Patel, MD

Ventilator-associated pneumonia (VAP) remains a diagnostic and management conundrum, with a well-documented risk of under-treatment of multidrug-resistant organisms that often leads to the utilization of broad-spectrum antibiotics. Coupled with a lack of a defined diagnostic standard, many patients are subject to unnecessary antibiotic therapy. A study published in the July 13 issue of Critical Care Medicine assesses the impact of discontinuing antibiotics, based on a negative quantitative bronchoalveolar lavage (BAL) culture alone.

The retrospective, observational study was performed in various medical and surgical intensive care units at Hartford Hospital in Connecticut. Subjects were included if they had a BAL or mini-BAL performed with growth defined as <104 CFU/mL, had received antibiotic therapy, and had one clinical sign or symptom of VAP. Patients were excluded if they received antibiotics for other indications. Mortality was the primary endpoint, with clinical resolution and superinfection as secondary assessments.

Eighty-nine patients were included in the study and were divided into an early discontinuation group (with antibiotics discontinued within one day of final BAL report) and a late discontinuation group. Groups were reasonably matched, though immunosuppressed patients were more frequently noted in the late discontinuation group. Mortality was not different between the two groups (25 percent vs. 30.6 percent, p=0.642), nor was there a difference in time to mortality. After multivariate logistic regression analyses, severity of illness was noted as a confounding variable, though controlling for Acute Physiology and Chronic Health Evaluation (APACHE) II score or Sequential Organ Failure Assessment (SOFA) score demonstrated no differences in mortality either. Of particular importance, persistent individual signs or symptoms of VAP were common (such as abnormal temperature, white blood cell count, Pao2:Fio2 ratio, and sputum production) but not significantly different.

The study has a number of limitations, most notably the retrospective design, the differences in immune status, and a limited sample size. Nonetheless, it provides some clinical solace to those looking to reduce unnecessary antibiotic utilization.

(Raman et al. Crit Care Med. 2013;41(7):1656-1663.)

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Sobering Data on Clinical Status at First Presentation for HIV Infection
Reviewed by Brian R. Wood, MD

Since the start of the epidemic, incredible advancements have been achieved in HIV diagnostic and treatment methods. However, new data published in Clinical Infectious Diseases suggests that little, if any, progress has been made in regards to clinical status at first presentation for HIV infection.

Investigators performed a systematic review and meta-regression of mean or median CD4 count of HIV-infected individuals at entry into care in developed countries. Forty-four studies were included in the analysis, which revealed no significant change in estimated CD4 count at entry into care from 1992 to 2011: +1.5 cells/μL per year (95 percent CI, -6.1 to 5.5 cells/μL per year). The estimated CD4 count of HIV-infected individuals newly presenting to care was 307 cells/μL in 1992 and 336 cells/μL in 2011. This result was unchanged when adjusted for type of study, inclusion criteria, location (United States versus elsewhere), or baseline demographics (based on a subanalysis of 15 studies). Furthermore, the estimated change in proportion of persons presenting with advanced HIV disease (CD4 count <200 cells/μL or AIDS) or presenting late to care (CD4 count <350 cells/μL or AIDS) were both <0.1 percent per year.

Late presentation to HIV care has serious implications for individual disease control and viral transmission. This data is startling because it indicates that despite significant achievements in the field of HIV in the last two decades, we have made little headway on clinical status at presentation to care. The data is limited by difficulty discerning diagnosis versus entry into care and lack of a standard definition for entry into care across the included studies. However, the result provides an important reminder of the need for universal HIV testing, early diagnosis, and improved access to care; only if we improve these factors will early antiretroviral therapy and treatment as prevention be successful.


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CDI Characteristics in the Community and the Influence of Empiric Treatment on Diagnosis
Reviewed by Manie Beheshti, MD, and Christopher J. Graber, MD, MPH

Once considered primarily an antibiotic-associated hospital-acquired disease, Clostridium difficile infection (CDI) is increasingly found in the community, and empiric treatment is often considered prior to diagnostic testing. Two recent studies highlight the epidemiology of community-associated CDI and the impact empiric treatment has on diagnosis.

In the July 22 issue of JAMA Internal Medicine, investigators identified and interviewed 944 patients from eight U.S. states diagnosed with community-onset CDI, defined as not having had an overnight stay in a health care facility in the 12 weeks prior to CDI diagnosis. Among them, 35.9 percent did not receive any antibiotics in the 12 weeks preceding their illness while 36.8 percent had received acid-suppressive therapy, mostly proton-pump inhibitors. Of the patients receiving antibiotics, the most common diagnoses were ear, sinus, and upper respiratory tract infections followed by dental cleaning and oral surgery. In reviewing health care exposures, 18 percent had no exposure while 40.7 percent had low-level exposure (defined as office visits to a physician/dentist or other outpatient visits). No link was found between CDI and food or animal exposure.

This study helps highlight the growing trend of CDI in the absence of prior antibiotic use and in patients with limited health care exposure. Further, it reinforces data pointing to acid suppressive therapy as a risk factor—perhaps broadening the role of antimicrobial stewardship.  As pointed out in the accompanying editorial, the increasing use of acid suppressants also raises the question of “why America has such an upset stomach.”

Another recent study from Clinical Infectious Diseases highlights the role that empiric therapy may have in reducing sensitivity of testing for CDI. Fifty-one CDI patients had testing with PCR, glutamate dehydrogenase, and toxigenic culture performed daily (either on stool or rectal swab) following the start of CDI treatment. Fourteen percent, 35 percent, and 49 percent of positive PCR tests reverted to negative one, two, and three days, respectively, into CDI treatment, a pattern similar to the other methodologies. The authors conclude that prompt testing of stool from patients suspected of having CDI is key in avoiding false-negative tests that have important therapeutic and infection control-related implications.

Taken together, these two studies suggest that clinicians should have a high index of suspicion and test promptly for CDI.

(Chitnis et al. JAMA Intern Med. 2013;173(14):1359-1367, Sepkowitz. JAMA Intern Med. 2013;173(14):1367-1368, and Sunkesula et al. Clin Infect Dis. 2013;57(4):494-500.)

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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:

September 15

  • Our Own Bacteriophage Communities May Contribute to Antibiotic Resistance
  • Antifungal Azoles, Fluoroquinolones, and Cardiac Repolarization
  • Cerebrospinal Fluid Pleocytosis After Fever-Associated Status Epilepticus

September 1

  • Decolonizing Surgical Drains
  • Tropheryma whipplei in the Lungs of HIV-Infected Patients

August 15

  • You Got Diphtheria How?
  • Voriconazole, Fluoride, Bones

August 1

  • Hyperbaric Oxygen Therapy for Healing of Diabetic Foot Ulcers?
  • HIV-1 at the Start
  • Wesselsbron Disease

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