Extra-urogenital infection by Mycoplasma hominis in transplant patients: two case reports and literature review.

BACKGROUND: Mycoplasma hominis is a facultative anaerobic bacterium commonly present in the urogenital tract. In recent years, M. hominis has increasingly been associated with extra-urogenital tract infections, particularly in immunosuppressed patients. Detecting M. hominis in a diagnostic laboratory can be challenging due to its slow growth rate, absence of a cell wall, and the requirements of specialized media and conditions for optimal growth. Consequently, it is necessary to establish guidelines for the detection of this microorganism and to request the appropriate microbiological work-up of immunosuppressed patients. CASE PRESENTATION: We hereby present two cases of solid organ transplant patients who developed M. hominis infection. Microscopic examination of the bronchial lavage and pleural fluid showed no microorganisms. However, upon inoculating the specimens onto routine microbiology media, the organism was successfully identified and confirmation was performed using 16S rDNA sequencing. Both patients received appropriate treatment resulting in the resolution of M. hominis infection. CONCLUSIONS: The prompt detection of M. hominis in a clinical specimen can have a significant impact on patient care by allowing for early intervention and ultimately resulting in more favorable clinical outcomes, especially in transplant patients.

SARS-CoV-2 antibodies: IgA correlates with severity of disease in early COVID-19 infection.

Timing of detection of immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and their use to support the diagnosis are of increasing interest. We used the Gold Standard Diagnostics ELISA to evaluate the kinetics of SARS-CoV-2 IgG, IgA, and IgM antibodies in sera of 82 hospitalized patients with polymerase chain reaction (PCR)-confirmed coronavirus disease 2019 (COVID-19). Serum samples were collected 1-59 days post-onset of symptoms (PoS) and we examined the association of age, sex, disease severity, and symptoms' duration with antibody levels. We also tested sera of 100 ambulatory hospital employees with PCR-confirmed COVID-19 and samples collected during convalescence, 35-57 days PoS. All but four of the admitted patients (95.1%) developed antibodies to SARS-CoV-2. Antibodies were detected within 7 days PoS; IgA in 60.0%, IgM in 53.3%, and IgG in 46.7% of samples. IgG positivity increased to 100% on Day 21. We did not observe significant differences in the rate of antibody development in regard to age and sex. IgA levels were highest in patients with a severe and critical illness. In multiple regression analyses, only IgA levels were statistically significantly correlated with critical disease (p = .05) regardless of age, sex, and duration of symptoms. Among 100 ambulatory hospital employees who had antibody testing after 4 weeks PoS only 10% had positive IgA antibodies. The most frequently isolated isotype in sera of employees after 30 days PoS was IgG (88%). IgA was the predominant immunoglobulin in early disease and correlated independently with a critical illness. IgG antibodies remained detectable in almost 90% of samples collected up to two months after infection.

SARS-CoV-2 antibody responses in solid organ transplant recipients.

Antibody responses among immunocompromised solid organ transplant recipients (SOT) infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) may be diminished compared to the general population and have not been fully characterized. We conducted a cohort study at our transplant center to investigate the rate of seroconversion for SARS-CoV-2 IgG antibodies among SOT recipients who were diagnosed with Coronavirus disease 2019 (COVID-19) and underwent serum SARS-CoV-2 IgG enzyme-linked immunosorbent assay (ELISA) testing. The 61 patients who were included in the final analysis underwent initial SARS-CoV-2 IgG testing at a median of 62 days (Interquartile range 55.0-75.0) from symptom onset. Note that, 51 of 61 patients (83.6%) had positive SARS-CoV-2 IgG results, whereas 10 (16.4%) had negative IgG results. Six (60%) out of 10 seronegative patients underwent serial IgG testing and remained seronegative up to 17 weeks post-diagnosis. Use of belatacept in maintenance immunosuppression was significantly associated with negative IgG antibodies to SARS-CoV-2 both in univariate and multivariate analyses (Odds ratio 0.04, p = .01). In conclusion, the majority of organ transplant recipients with COVID-19 in our study developed SARS-CoV-2 antibodies. Further longitudinal studies of the durability and immunologic role of these IgG responses and the factors associated with lack of seroconversion are needed.

Recognizing Cutibacterium acnes as a cause of infectious pericarditis: A case report and review of literature.

Cutibacterium acnes is an anaerobic bacterium commonly thought of as a culture contaminant rather than a pathogen. We present a case of Cutibacterium acnes pericarditis in a 22-year-old immunocompetent woman managed with surgical pericardial window and a 4-week course of penicillin G and review related literature on Cutibacterium acnes pericarditis.

T2 magnetic resonance assay for the rapid diagnosis of candidemia in whole blood: a clinical trial.

BACKGROUND: Microbiologic cultures, the current gold standard diagnostic method for invasive Candida infections, have low specificity and take up to 2-5 days to grow. We present the results of the first extensive multicenter clinical trial of a new nanodiagnostic approach, T2 magnetic resonance (T2MR), for diagnosis of candidemia. METHODS: Blood specimens were collected from 1801 hospitalized patients who had a blood culture ordered for routine standard of care; 250 of them were manually supplemented with concentrations from <1 to 100 colony-forming units (CFUs)/mL for 5 different Candida species. RESULTS: T2MR demonstrated an overall specificity per assay of 99.4% (95% confidence interval [CI], 99.1%-99.6%) with a mean time to negative result of 4.2 ± 0.9 hours. Subanalysis yielded a specificity of 98.9% (95% CI, 98.3%-99.4%) for Candida albicans/Candida tropicalis, 99.3% (95% CI, 98.7%-99.6%) for Candida parapsilosis, and 99.9% (95% CI, 99.7%-100.0%) for Candida krusei/Candida glabrata. The overall sensitivity was found to be 91.1% (95% CI, 86.9%-94.2%) with a mean time of 4.4 ± 1.0 hours for detection and species identification. The subgroup analysis showed a sensitivity of 92.3% (95% CI, 85.4%-96.6%) for C. albicans/C. tropicalis, 94.2% (95% CI, 84.1%-98.8%) for C. parapsilosis, and 88.1% (95% CI, 80.2%-93.7%) for C. krusei/C. glabrata. The limit of detection was 1 CFU/mL for C. tropicalis and C. krusei, 2 CFU/mL for C. albicans and C. glabrata, and 3 CFU/mL for C. parapsilosis. The negative predictive value was estimated to range from 99.5% to 99.0% in a study population with 5% and 10% prevalence of candidemia, respectively. CONCLUSIONS: T2MR is the first fully automated technology that directly analyzes whole blood specimens to identify species without the need for prior isolation of Candida species, and represents a breakthrough shift into a new era of molecular diagnostics. CLINICAL TRIALS REGISTRATION: NCT01752166.

Colonization with toxinogenic C. difficile upon hospital admission, and risk of infection: a systematic review and meta-analysis.

OBJECTIVES: It has been suggested that colonization with C. difficile protects from infection. Nevertheless, the association between carriage of toxinogenic strains and ensuing C. difficile infections (CDIs) has not been studied. METHODS: We searched PubMed and EMBASE databases up to 20 June 2014, using the term "difficile". Our primary outcomes of interest included the prevalence of isolation of toxinogenic C. difficile or its toxins from asymptomatic patients on hospital admission through stool or rectal swab testing and the risk of ensuing infection among colonized and noncolonized patients. Data on previous hospitalization, antibiotic, and proton pump inhibitor (PPI) use and prior CDIs among colonized and noncolonized patients were also extracted. RESULTS: Nineteen out of 26,081 studies on 8,725 patients were included. The pooled prevalence of toxinogenic C. difficile colonization was 8.1% (95% confidence interval (CI) 5.7-11.1%), with an increasing trend over time (P=0.003), and 10.0% (95% CI 7.1-13.4%) among North American studies. Patients colonized upon hospital admission had a 5.9 times higher risk of subsequent CDIs compared with noncolonized patients (relative risk (RR) 5.86; 95% CI 4.21-8.16). The risk of CDI for colonized patients was 21.8% (95% CI 7.9-40.1%), which was significantly higher than that of noncolonized patients (3.4%; 95% CI 1.5-6.0%; P=0.03), with an attributable risk of 18.4%. History of hospitalization during the previous 3 months was associated with a higher risk of colonization (RR 1.63; 95% CI 1.13-2.34), as opposed to previous antibiotic (RR 1.07; 95% CI 0.75-1.53) and PPI use (RR 1.44; 95% CI 0.94-2.23), as well as history of CDI (RR 1.45; 95% CI 0.66-3.18) that had no impact. CONCLUSIONS: Over 8% of admitted patients are carriers of toxinogenic C. difficile with an almost 6 times higher risk of infection. These findings update current knowledge regarding the contribution of colonization in CDI epidemiology and stress the importance of preventive measures toward colonized patients.

Methicillin-resistant Staphylococcus aureus prevention strategies in the ICU: a clinical decision analysis*.

OBJECTIVES: ICUs are a major reservoir of methicillin-resistant Staphylococcus aureus. Our aim was to estimate costs and effectiveness of methicillin-resistant Staphylococcus aureus prevention policies. DESIGN AND INTERVENTIONS: We evaluated three up-to-date methicillin-resistant Staphylococcus aureus prevention policies, namely, 1) nasal screening and contact precautions of methicillin-resistant Staphylococcus aureus-positive patients; 2) nasal screening, contact precautions, and decolonization (targeted decolonization) of methicillin-resistant Staphylococcus aureus carriers; and 3) universal decolonization without screening. We implemented a decision-analytic model with deterministic and probabilistic analyses. Methicillin-resistant Staphylococcus aureus infections averted, quality-adjusted life years gained, and incremental cost-effectiveness ratios were calculated. Cost-effectiveness planes and acceptability curves were plotted for various willingness-to-pay thresholds to address uncertainty. MEASUREMENTS AND MAIN RESULTS: At base-case scenario, universal decolonization was the dominant strategy; it averted 1.31% and 1.59% of methicillin-resistant Staphylococcus aureus infections over targeted decolonization and screening and contact precautions, respectively, and saved $16,203/quality-adjusted life year over targeted decolonization and 14,562/quality-adjusted life year over screening and contact precautions. Results were robust in sensitivity analysis for a wide range of input variables. In probabilistic analysis, universal decolonization increased quality-adjusted life years by 1.06% (95% CI, 1.02-1.09) over targeted decolonization and by 1.29% (95% CI, 1.24-1.33) over screening and contact precautions; universal decolonization resulted in average savings of $172 (95% CI, $168-$175) and $189 (95% CI, $185-$193) over targeted decolonization and screening and contact precautions, respectively. With willingness-to-pay threshold per quality-adjusted life year gained ranging from $0 to $50,000, universal decolonization was dominant over targeted decolonization in 67.5-75.4% and dominant over screening and contact precautions in 66.0-75.4%. CONCLUSIONS: In the ICU setting, universal decolonization outperforms the other two strategies and is likely to be cost-effective even at low willingness-to-pay thresholds. Assuming 700 annual ICU admissions in an average 12-bed ICU, the projected annual savings reach $129,500 to $135,100.

Vancomycin-resistant enterococci colonization among dialysis patients: a meta-analysis of prevalence, risk factors, and significance.

BACKGROUND: Vancomycin-resistant enterococci (VRE) have become important nosocomial pathogens causing outbreaks worldwide. Patients undergoing dialysis represent a vulnerable population due to their comorbid conditions, frequent use of antibacterial agents, and frequent contact with health care settings. STUDY DESIGN: Systematic review and meta-analysis of cross-sectional studies of screening for VRE colonization. SETTING & POPULATION: Patients receiving long-term dialysis treatment. SELECTION CRITERIA FOR STUDIES: We performed a systematic literature search of PubMed and EMBASE databases to identify studies performing screening for VRE colonization among dialysis patients. PREDICTOR: Region, recent use of vancomycin or other antibiotics, previous hospitalization. OUTCOMES: (1) VRE colonization and (2) rate of VRE infection among colonized and noncolonized individuals. Relative effects were expressed as ORs and 95% CIs. RESULTS: We identified 23 studies that fulfilled the inclusion criteria and provided data for 4,842 dialysis patients from 100 dialysis centers. The pooled prevalence of VRE colonization was 6.2% (95% CI, 2.8%-10.8%), with significant variability between centers. The corresponding number for North American centers was 5.2% (95% CI, 2.8%-8.2%). Recent use of any antibiotic (OR, 3.62; 95% CI, 1.22-10.75), particularly vancomycin (OR, 5.15; 95% CI, 1.56-17.02), but also use of antibiotics other than vancomycin (OR, 2.92; 95% CI, 0.99-8.55) and recent hospitalization (OR, 4.55; 95% CI, 1.93-10.74) significantly increased the possibility of a VRE-positive surveillance culture. Colonized patients had a significantly higher risk of VRE infection (OR, 21.62; 95% CI, 5.33-87.69) than their noncolonized counterparts. LIMITATIONS: In 19 of 23 studies, a low percentage of dialysis patients (<80%) consented to participate in the screening procedure. 4 of 8 studies in which patients were followed up for more than 1 month reported VRE infections and only 5 of 23 studies provided extractable data for antibiotic consumption prior to screening. CONCLUSIONS: VRE colonization is prevalent in dialysis centers. Previous antibiotic use, in particular vancomycin, and recent hospitalization are important predicting factors of colonization, whereas the risk of VRE infection is significantly higher for colonized patients.

Meta-analysis of methicillin-resistant Staphylococcus aureus colonization and risk of infection in dialysis patients.

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.

Prevalence of and risk factors for methicillin-resistant Staphylococcus aureus colonization in HIV infection: a meta-analysis.

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.

Antimicrobial lock solutions as a method to prevent central line-associated bloodstream infections: a meta-analysis of randomized controlled trials.

BACKGROUND: Antimicrobial lock solutions may be an effective strategy to prevent catheter-associated infections. However, there remains concern about their efficacy and safety. METHODS: To investigate the efficacy of antimicrobial lock therapy to prevent central line-associated bloodstream infections (CLABSIs), we performed a systematic search of PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov, from the earliest date up to 31 December 2013. Studies were eligible if they were randomized controlled trials comparing antimicrobial lock solutions to heparin and if they provided an appropriate definition of infection. RESULTS: The 23 included studies reported data on 2896 patients, who were predominantly adult patients undergoing hemodialysis (16/23 studies), but also adult and pediatric oncology patients, critically ill neonates, and patients receiving total parenteral nutrition. The use of antimicrobial lock solutions led to a 69% reduction in CLABSI rate (relative risk [RR], 0.31; 95% confidence interval [CI], .24-.40) and a 32% reduction in the rate of exit site infections (RR, 0.68; 95% CI, .49-.95) compared with heparin, without significantly affecting catheter failure due to noninfectious complications (RR, 0.83; 95% CI, .65-1.06). All-cause mortality was not different between the groups (RR, 0.84; 95% CI .64-1.12). Neither the type of antimicrobial solution nor the population studied, affected the relative reduction in CLABSIs, which also remained significant among studies reporting baseline infection rates of <1.15 per 1000 catheter-days, and studies providing data for catheter-related bloodstream infections. Publication and selective reporting bias are a concern in our study and should be acknowledged. CONCLUSIONS: Antimicrobial lock solutions are effective in reducing risk of CLABSI, and this effect appears to be additive to traditional prevention measures.

PCR in diagnosis of invasive aspergillosis: a meta-analysis of diagnostic performance.

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.

Utility of incorporation of beta-D-glucan and T2Candida testing for diagnosis and treatment of candidemia.

The additive role of non-culture-based methods for the diagnosis of candidemia remains unknown. We evaluated 2 clinical practices followed in our hospitals for the diagnosis of candidemia, namely practice#1 including a combination of blood cultures and T2Candida, and practice#2 that also included Beta-D-glucan (BDG). Three out of 96 patients testing positive with practice#1 received a complete antifungal course. Of the 120 patients evaluated with practice#2, 29 were positive. Only 55.2% of those received a complete course. We observed significant differences in antifungal utilization, with 268.5 antifungal days/1000 patient-days for practice#1, as opposed to 371.9 days for practice#2, a nearly 40% difference. However, we found similar rates of antifungal discontinuation among negative patients at 3 days of testing (36.8% and 37.0% respectively). No differences were detected in death and/or subsequent diagnosis of candidemia. In summary, addition of BDG was interpreted variably by clinicians, was associated with an increase in antifungal utilization, and did not correlate with measurable clinical benefits for patients.

Evaluation of BioFire® FilmArray® Pneumonia Panel in Bronchoalveolar Lavage Samples From Immunocompromised Patients With Suspected Pneumonia.

Objectives Immunocompromised patients, specifically those with solid organ transplants or cancer on chemotherapy, are at particularly high risk of severe pneumonia and opportunistic infections. In select patients, bronchoalveolar lavage (BAL) is performed to provide high-quality samples for analysis. We compare BioFire® FilmArray® Pneumonia Panel (BioFire Diagnostics, Salt Lake City, Utah, United States), a multiplex polymerase chain reaction (PCR) assay, with standard of care diagnostics in BAL samples from immunocompromised patients to identify opportunities for this test to affect clinical decision making. Methods Patients hospitalized with pneumonia based on clinical and radiographic findings who underwent evaluation with bronchoscopy between May 2019 to January 2020 were reviewed. Among those patients undergoing bronchoscopy, those who were immunocompromised were selected for inclusion in the study. BAL specimens submitted to the microbiology laboratory were chosen based on as part of the internal validation of the panel in comparison with sputum culture at our hospitals. We compared the outcomes of the multiplex PCR assay with traditional culture methods and evaluated the role of PCR assay in de-escalating antimicrobial therapy. Results Twenty-four patients were identified for testing with the multiplex PCR assay. Of the 24 patients, 16 were immunocompromised, all with solid or hematological malignancy or a history of organ transplant. Seventeen individual BAL samples from the 16 patients were reviewed. BAL culture results and the multiplex PCR assay were in agreement in 13 samples (76.5%). In four cases, the multiplex PCR assay identified a possible causative pathogen not detected by standard workup. The median time to de-escalation of antimicrobials was three days (interquartile range (IQR) 2-4) from the day of collection of the BAL samples. Conclusions Studies have established the additive role of multiplex PCR testing in addition to traditional diagnostic tools like sputum culture in diagnosing the etiology of pneumonia. Limited data exist specifically looking at immunocompromised patients, in whom a timely and accurate diagnosis is particularly important. There is a potential benefit for performing multiplex PCR assays as an additive diagnostic tool in BAL samples for these patients.