Faculty Bibliography

BACKGROUND:Human immunodeficiency virus (HIV)-infected individuals who are colonized with methicillin-resistant Staphylococcus aureus (MRSA) have increased risk for MRSA infection. We conducted a meta-analysis of published studies to estimate the prevalence of MRSA colonization in this population. METHODS:We performed a systematic literature review and meta-analysis. The PubMed and Embase databases were searched and studies reporting prevalence of MRSA colonization among HIV-infected individuals were included. RESULTS:Among 7940 citations, 32 studies reporting data on 6558 HIV-infected individuals were considered eligible for our meta-analysis. We found that 6.9% (95% confidence interval [CI], 4.8-9.3) of individuals with HIV infection are MRSA carriers, with the corresponding figure across North American studies being 8.8% (95% CI, 6.0-12.2). History of hospitalization during the previous 12 months was associated with a 3.1 times higher risk of MRSA colonization (risk ratio [RR], 3.11 [95% CI, 1.62-5.98]). Previous or current incarceration was also associated with a higher risk for carriage (RR, 1.77 [95% CI, 1.26-2.48]). Current antiretroviral therapy or use of trimethoprim-sulfamethoxazole did not impact the risk of MRSA carriage (RR, 1.02 [95% CI, .64-1.63] and 1.45 [95% CI, .69-3.03], respectively). Extranasal screening increased the detection of MRSA colonization by at least 31.6% (95% CI, 15.8-50.0). The added yield from groin screening was 19.3% (95% CI, 11.5-28.5), from perirectal screening 18.5% (95% CI, 7.4-33.2), and from throat cultures 17.5% (95% CI, 12.0-24). CONCLUSIONS:Individuals with HIV infection constitute a highly vulnerable population for MRSA colonization, and prior exposure to hospital or incarceration are significant factors. Nasal screening alone will underestimate the rate of colonization by at least one-third.

Invasive aspergillosis is a difficult-to-diagnose infection with a high mortality rate that affects high-risk groups such as patients with neutropenia and hematologic malignancies. We performed a bivariate meta-analysis of diagnostic data for an Aspergillus sp. PCR assay with blood specimens from high-risk hematology patients. We included all studies involving human subjects that assessed the performance of any PCR assay for invasive aspergillosis in whole blood or serum and that used the European Organization for the treatment of Cancer/Mycoses Study Group criteria as a reference standard. Three investigators independently searched the literature for eligible studies and extracted the data. Out of a total of 37 studies, 25 met strict quality criteria and were included in our evidence synthesis. Twenty-five studies with 2,595 patients were analyzed. The pooled diagnostic performance of whole-blood and serum PCR assays was moderate, with a sensitivity and specificity of 84% (95% confidence interval [CI], 75 to 91%) and 76% (95% CI, 65 to 84%), respectively, suggesting that a positive or negative result is unable, on its own, to confirm or exclude a suspected infection. The performance of a PCR assay of serum was not significantly different from that of whole blood. Notably, at least two positive PCR test results were found to have a specificity of 95% and a sensitivity of 64% for invasive infection, achieving a high positive likelihood ratio of 12.8. Importantly, the European Aspergillus PCR Initiative (EAPCRI) recommendations improved the performance of the PCR even further when at least two positive specimens were used to define PCR positivity. In conclusion, two positive PCR results should be considered highly indicative of an active Aspergillus sp. infection. Use of the EAPCRI recommendations by clinical laboratories can further enhance PCR performance.

Patients undergoing dialysis are particularly vulnerable to methicillin-resistant Staphylococcus aureus (MRSA) infections. We performed a meta-analysis of published studies to estimate the prevalence of MRSA colonization in dialysis patients, time trends, and long-term risk of subsequent MRSA infections. Our search of the PubMed and Embase databases returned 5743 nonduplicate citations, from which we identified 38 relevant studies that included data on 5596 dialysis patients. The estimated prevalence of MRSA colonization was 6.2% (95% confidence interval [95% CI], 4.2% to 8.5%). The prevalence increased over time but remained stable after 2000. Stratification of patients according to dialysis modality and setting revealed that 7.2% (95% CI, 4.9% to 9.9%) of patients on hemodialysis were colonized with MRSA compared with 1.3% (95% CI, 0.5% to 2.4%) of patients on peritoneal dialysis (P=0.01), and that a statistically significant difference existed in the percentage of colonized inpatients and outpatients (14.2% [95% CI, 8.0% to 21.8%] versus 5.4% [95% CI, 3.5% to 7.7%], respectively; P=0.04). Notably, the risk of developing MRSA infections increased among colonized hemodialysis patients compared with noncolonized patients (relative risk, 11.5 [95% CI, 4.7 to 28.0]). The long-term (6-20 months) probability of developing a MRSA infection was 19% among colonized hemodialysis patients compared with only 2% among noncolonized patients. In summary, 6.2% of dialysis patients are MRSA colonized, and the average prevalence of colonization has remained stable since 2000. Colonization in hemodialysis patients is associated with increased risk of MRSA infection.

The burden of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE) colonization among the increasing number of solid organ transplant patients has not been systematically explored. We searched PubMed and EMBASE for pertinent articles, performed a meta-analysis of prevalence across eligible studies and estimated the risk of ensuing MRSA or VRE infections relative to colonization status. We stratified effects in the pretransplant and posttransplant period. Twenty-three studies were considered eligible. Seventeen out of 23 (74%) referred to liver transplants. Before transplantation, the pooled prevalence estimate for MRSA and VRE was 8.5% (95% confidence interval [CI] 3.2–15.8) and 11.9% (95% CI 6.8–18.2), respectively. MRSA estimate was influenced by small studies and was lower (4.0%; 95% CI 0.4–10.2) across large studies (>200 patients). After transplantation, the prevalence estimates were 9.4% (95% CI 3.0–18.5) for MRSA and 16.2% (95% CI 10.7–22.6) for VRE. Pretransplant as well as posttransplant MRSA colonization significantly increased the risk for MRSA infections (pooled risk ratio [RR] 5.51; 95% CI 2.36–12.90 and RR 10.56; 95% CI 5.58–19.95, respectively). Pretransplant and posttransplant VRE colonization were also associated with significant risk of VRE infection (RR 6.65; 95% CI 2.54–17.41 and RR 7.93; 95% CI 2.36–26.67, respectively). Solid organ transplantation is a high-risk setting for MRSA and VRE colonization, and carrier state is associated with infection. Upgraded focus in prevention and eradication strategies is warranted.

BACKGROUND AND OBJECTIVE/OBJECTIVE:Methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of morbidity and mortality in NICUs and PICUs. Our objective was to assess the burden of MRSA colonization on admission, study the time trends, and examine the significance of MRSA colonization in this population. METHODS:PubMed and Embase databases were consulted. Studies that reported prevalence of MRSA colonization on ICU admission were selected. Two authors independently extracted data on MRSA colonization and infection. RESULTS:We identified 18 suitable articles and found an overall prevalence of MRSA colonization of 1.9% (95% confidence interval [CI] 1.3%-2.6%) on admission to the NICU or PICU, with a stable trend over the past 12 years. Interestingly, 5.8% (95% CI 1.9%-11.4%) of outborn neonates were colonized with MRSA on admission to NICU, compared with just 0.2% (95% CI 0.0%-0.9%) of inborn neonates (P = .01). The pooled acquisition rate of MRSA colonization was 4.1% (95% CI 1.2%-8.6%) during the NICU and PICU stay and was as high as 6.1% (95% CI 2.8%-10.6%) when the NICU population was studied alone. There was a relative risk of 24.2 (95% CI 8.9-66.0) for colonized patients to develop a MRSA infection during hospitalization. CONCLUSIONS:In the NICU and PICU, there are carriers of MRSA on admission, and MRSA colonization in the NICU is almost exclusively associated with outborn neonates. Importantly, despite infection control measures, the acquisition rate is high, and patients colonized with MRSA on admission are more likely to suffer a MRSA infection during hospitalization.

BACKGROUND:Graft-versus-host Disease (GvHD) prophylaxis after allogeneic hematopoietic stem-cell transplantation (HSCT) is an ongoing effort but relative effects of different policies are not systematically explored. METHODS:We systematically reviewed 30-year evidence on GvHD prophylaxis and quantified the relative effect of different policies using a network meta-analysis. We searched PubMed and the Cochrane Library for randomized studies on the topic. The primary outcome of interest was grade II-IV acute GvHD over 0 or I (with odds ratio OR <1 denoting benefit). FINDINGS/RESULTS:Thirty-three eligible studies that enrolled 3,440 patients (published up to June 2014), provided data on seven immunosuppressive drugs namely cyclosporin A (CsA), methotrexate (MTX), anti-thymocyte globulin (ATG), mycophenolate mofetil (MMF), tacrolimus, sirolimus or corticosteroids and their combinations to calculate 14 direct and 21 indirect effects. The majority of trials (32/33) referred to myeloablative conditioning and sibling transplants (25/33). Tacrolimus/MTX (OR 0.44; 95% 0.27-0.70, number needed to treat to benefit, i.e. to avert a case of II-IV GvHD, NNTB = 5) and ATG/CsA/MTX (OR 0.45; 95%CI 0.26-0.78; NNTB = 5) were superior over CsA/MTX. ATG/CsA/MTX did not differ from tacrolimus/MTX (indirect evidence). Sirolimus-based prophylaxis outperformed CsA/MTX (OR 0.10; 95%CI 0.02-0.49, NNTB = 4) and marginally outperformed tacrolimus/MTX (OR 0.22; 95%CI 0.05-1.11). Add-on corticosteroids had no benefit over CsA/MTX. CONCLUSIONS:Tacrolimus/MTX and ATG/CsA/MTX were the outperformers over CsA/MTX, but sirolimus-based regimens showed also potential. More randomized data are needed for reduced-intensity conditioning, as well as for MMF and sirolimus-containing regimens.