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July/August 2015
Journal Club
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, FIDSA, in each issue of Clinical Infectious Diseases.

Echocardiography and Cardiac Device Removal, if Present: Necessary for All with Staphylococcus Bacteremia?
Reviewed by Manie Beheshti, MD

Two commonly encountered quandaries for ID clinicians are determining the utility of transesophageal echocardiograms (TEE) and the need for removal of a cardiovascular implantable electronic device (CIED), when present, in patients with Staphylococcus aureus bacteremia (SAB). Recent data from the Mayo Clinic provides a simple framework to aid clinicians in these situations.

In a recent issue of Clinical Infectious Diseases, researchers retrospectively reviewed nearly 700 patients with SAB over a five-year period. Using multivariable analysis, three independent predictors of infective endocarditis were identified: SAB acquired in the community, cardiac device presence, and prolonged bacteremia (72 hours or greater). Using a scoring system to maximize sensitivity, specificity, and negative predictive value, the authors propose a two-stage scoring system using the above predictors.

A high score on day one of SAB was 96 percent specific for infective endocarditis (IE), leading to the recommendation to pursue TEE (see Figure 3 in the study for a detailed flowchart). In those with low scores on day one, a second analysis was made on day five, at which time a low score carried a greater than 98 percent sensitivity and negative predictive value for IE, thus allowing for deferral of TEE.

In the February 2015 issue of Circulation: Arrhythmia and Electrophysiology, researchers from the same institution identified high-risk features in those with a CIED (permanent pacemaker, greater than one device-related procedure, and duration of SAB for four or more days). Using similar analytics, they conclude that in the absence of these risks, those patients without evidence of generator pocket infection may be monitored closely without device extraction.

These two studies aim to answer a commonly encountered question for patients with SAB. Although prospective studies are needed to validate these data, the authors are able to provide a much needed framework to aid the clinician’s risk assessment for each patient. While clinical judgment supersedes any algorithm, these informative studies certainly help provide further evidence to support clinical decisions.

(Palraj et al. Clin Infect Dis. 2015;61(1):18-28 and Sohail et al. Circ Arrhythm and Electrophysiol. 2015;8:137-144)

Addition of IV Metronidazole to Oral Vancomycin for Severe C. difficile Infection: Data to Support a Common Clinical Practice
Reviewed by Christopher J. Graber, MD, MPH, FIDSA

Intravenous (IV) metronidazole is commonly used in combination with oral vancomycin for the treatment of severe Clostridium difficile infection (CDI), but the practice carries only a C-III (expert opinion) recommendation in the most recent SHEA-IDSA guidelines. However, a recent study published in Clinical Infectious Diseases provides some data to support the approach.

Eighty-eight patients who were admitted to the intensive care unit (ICU) at a single institution from June 2007 to September 2012 and met at least three of seven pre-specified criteria for severe CDI were analyzed; 44 patients who received IV metronidazole in addition to oral vancomycin were matched to 44 who did not, based on Acute Physiology and Chronic Health Evaluation II (APACHE-II) scores. Patients in the IV metronidazole group had significantly higher leukocytosis and moderate to severe renal disease and lower mean arterial pressures.

The group receiving IV metronidazole had an in-hospital mortality of 15 days, compared to 21 days for the monotherapy group (p=0.03), though other outcomes (clinical success at day 6, 10, and 21; length of stay in hospital or ICU after CDI diagnosis) were similar between the two groups. In a multivariable analysis, only two factors were independently associated with survival: serum albumin (OR 0.87, p=0.011) and receipt of IV metronidazole (OR 4.54, p=0.008).

This study has limitations: its retrospective single-center nature, its relatively small number of patients, a higher (yet not statistically significant) proportion of patients in the IV metronidazole group receiving rectal vancomycin (18.2 percent vs. 4.5 percent), and differences in dosing of oral vancomycin between the two groups (somewhat more aggressive in the group receiving IV metronidazole). Nonetheless, this study provides important insights regarding optimal management of one of our most common life-threatening diseases.

(Rokas et al. Clin Infect Dis. 2015; published online May 29, 2015, doi: 10.1093/cid/civ409)

Comparing Interferon-γ Release Assay and Tuberculin Skin Testing for TB Screening in Exposed Health Care Workers
Reviewed by Zeina Kanafani, MD, MS

The value of the interferon-γ release assay (IGRA) in the diagnosis of latent tuberculosis (TB) infection among health care workers (HCWs) has not been fully elucidated. A recent Infection Control & Hospital Epidemiology study, conducted at 14 hospitals in France, compared the efficiency of the tuberculin skin test (TST) to that of IGRA in diagnosing latent TB infection among HCWs at high risk of TB exposure.

Upon study entry, all subjects had a TST and IGRA, and both tests were repeated in one year. The cut-off for TST positivity was set at ≥10 mm of induration, and conversion was defined as an increase in induration of ≥10 mm from baseline. IGRA was performed using QuantiFERON TB Gold (QFT-G). Indeterminate results with QFT-G were further tested by the T-SPOT TB assay.

A total of 807 participants underwent baseline testing, with 113 (14 percent) having a positive IGRA and 446 (55.3 percent) having a positive TST. Almost all HCWs had received the bacille Calmette-Guérin (BCG) vaccine. IGRA positivity correlated with TST induration such that IGRA was more likely to be positive as TST induration increased (2.8 percent with TST 0-4 mm induration vs. 25.2 percent with TST ≥ 15 mm induration). At one-year follow-up, the conversion rate was 9.0 percent by IGRA and 2.5 percent by TST. Only one participant had conversion by both assays. In addition, quantitative testing of QFT-G revealed a reversion rate at one-year follow-up of 40.0 percent if baseline QFT-G was 0.35-0.69 IU/mL, and 6.1 percent if baseline QFT-G was ≥1 IU/mL (p = 0.001).

In this cohort of BCG-vaccinated, high-risk HCWs, the prevalence of positive TST was higher than that of positive IGRA. IGRA testing was associated with higher conversion rates compared to TST testing, and reversion rates were high with borderline values of QFT-G. Given these results, and the poor correlation between TST and IGRA positivity, the value of IGRA in the diagnosis of latent TB infection remains uncertain.

(Lucet et al. Infect Control Hosp Epidemiol. 2015;36(5):569-574.)

Synergy Despite Resistance: Colistin-Tigecycline for XDR A. baumannii and Excess Mortality Compared to Colistin-Carbapenem
Reviewed by Nirav Patel, MD

Extensively drug-resistant (XDR) Acinetobacter baumannii, susceptible only to colistin and tigecycline, is a frequent and deadly pathogen. Treatment is hampered with poor outcomes using monotherapy, as well as the development of resistance. Combination therapy has been advocated, although well-designed studies have been limited due to challenges in study design, recruitment, and heterogeneous study populations. Furthermore, initially promising data for the combination of colistin and rifampin was later refuted in a larger, randomized trial that found no mortality benefit.

Given this background, researchers initiated a prospective, observational study at three large hospitals in Taiwan from 2010 to 2013, with the results recently published in Critical Care Medicine. Patients were included if they had bacteremia from XDR A. baumannii (genospecies 2) and were prescribed colistin in combination with tigecycline or a carbapenem.

Of 176 patients screened, 31 patients were in the colistin-tigecycline arm and 29 in the colistin-carbapenem arm. The groups were fairly evenly matched with regards to severity. Crude 14-day mortality was not significantly different (35 percent in the colistin-tigecycline arm versus 15 percent in the colistin-carbapenem arm [p=0.105]). Breakthrough XDR bacteremia was noted in 18 percent of the colistin-tigecycline patients versus 0 percent in the colistin-carbapenem group (p=0.059). Excess 14-day mortality was seen the colistin-tigecycline patients, when the tigecycline minimum inhibitory concentration was >2 mg/L compared to colistin-carbapenem (hazard ratio 6.93, p=0.009).

As noted in a related editorial, there are a number of limitations with this study, including its size and non-randomized nature. However, despite in vitro resistance, the use of a carbapenem in combination with colistin offers advantages compared to tigecycline. This may be related to differences in the mechanism of action or the low serum drug levels of tigecycline. A prospective, randomized trial is needed to definitively answer the question. Until then, it seems reasonable to adopt the colistin-carbapenem combination for this formidable pathogen.

(Cheng et al. Crit Care Med. 2015;43(6):1194-204.)

Preexposure Prophylaxis for Serodiscordant Couples who Wish to Conceive
Reviewed by Brian R. Wood, MD

Many heterosexual serodiscordant couples wish to conceive yet believe they have no options. If the female partner is HIV-infected, self-insemination during ovulation is a viable strategy. If the male partner is HIV-infected, options were traditionally limited to sperm washing and other costly procedures. Now, antiretroviral treatment-as-prevention combined with preexposure prophylaxis (PrEP) opens the door to new approaches. Data to guide these decisions were previously limited to small observational studies and expert opinion.

In The Journal of Infectious Diseases, researchers recently modeled the average annual probability of a “successful outcome” (having a child and remaining HIV-uninfected) or “unsuccessful outcome” (not having a child and becoming HIV-infected) for women age 18 to 49 who have condomless sex with an HIV-infected man. Investigators modeled outcomes for the “ideal circumstance” (suppressive ART for the male partner, STI screening and treatment, daily PrEP for the female partner, and sex only during days of ovulation) or “suboptimal circumstance” (same parameters except with sex distributed throughout the menstrual cycle).

Under the ideal circumstance, the likelihood of a successful outcome was 29.1 percent with ART alone and only increased to 29.2 percent with the addition of PrEP (P=0.45); the likelihood of an unsuccessful outcome was 0.1 percent with ART plus PrEP and 0.4 percent with ART alone. In the suboptimal circumstance, the likelihood of success was 26.8 percent with ART alone and increased to 27.3 percent with adjunctive PrEP (P<0.0001), whereas the probability of an unsuccessful outcome with ART plus PrEP was 0.8 percent. In both circumstances, older maternal age decreased the likelihood of success.

This intriguing analysis suggests that, under ideal circumstances, PrEP does not provide significant additive benefit to suppressive ART for couples who wish to conceive. Importantly, even with suppressive ART, the frequency of condomless sex impacted transmission risk, which has implications for PrEP counseling in general. The authors are developing a tool to estimate transmission risk based on modifiable factors, which will aid in counseling serodiscordant couples. A variable that can’t be measured in a modeling study is the peace of mind that PrEP offers, which should also be considered.

(Hoffman et al. J Infect Dis. 2015; published online June 19, 2015; doi: 10.1093/infdis/jiv305)

Back to Top

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

July 15
  • Exposure to Antibiotics May Be Unavoidable in China
  • Candida Endocarditis: Surgery May Not Be Necessary for All
  • Case Vignette: Is Valve-in-Valve-in-Valve-in-Valve Coming Next?
July 1
  • Capillariasis
  • Acute HIV Infection: When Fitness Is a Bad Thing
  • Case Vignette: Apparent Transmission of Scedosporium From an Organ Donor Who Experienced Near-drowning

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