A Case of New Delhi Metallo-ß-Lactamases (NDM) Citrobacter sedlakii Osteomyelitis Successfully Treated With Ceftazidime-Avibactam and Aztreonam.

There have been an increase in multi-drug resistant (MDR) organisms causing infections with high mortality and morbidity. Bacteria that carry metallo-ß-lactamases (MBLs) are particularly dangerous. Novel antibiotic combinations, such as ceftazidime-avibactam with aztreonam, are in clinical trials for the treatment of MBL-harboring bacteria. We discuss the case of a 39-year-old patient who presented with tibial osteomyelitis growing MBL-producing Citrobacter sedlakii. He was successfully treated with ceftazidime-avibactam and aztreonam combination therapy. We discuss the importance of developing new antibiotic regimens for the growing threat of MDR organisms with special consideration of MBL.

A Laboratory Medicine Best Practices Systematic Review and Meta-analysis of Nucleic Acid Amplification Tests (NAATs) and Algorithms Including NAATs for the Diagnosis of Clostridioides (Clostridium) difficile in Adults.

The evidence base for the optimal laboratory diagnosis of Clostridioides (Clostridium) difficile in adults is currently unresolved due to the uncertain performance characteristics and various combinations of tests. This systematic review evaluates the diagnostic accuracy of laboratory testing algorithms that include nucleic acid amplification tests (NAATs) to detect the presence of C. difficile The systematic review and meta-analysis included eligible studies (those that had PICO [population, intervention, comparison, outcome] elements) that assessed the diagnostic accuracy of NAAT alone or following glutamate dehydrogenase (GDH) enzyme immunoassays (EIAs) or GDH EIAs plus C. difficile toxin EIAs (toxin). The diagnostic yield of NAAT for repeat testing after an initial negative result was also assessed. Two hundred thirty-eight studies met inclusion criteria. Seventy-two of these studies had sufficient data for meta-analysis. The strength of evidence ranged from high to insufficient. The uses of NAAT only, GDH-positive EIA followed by NAAT, and GDH-positive/toxin-negative EIA followed by NAAT are all recommended as American Society for Microbiology (ASM) best practices for the detection of the C. difficile toxin gene or organism. Meta-analysis of published evidence supports the use of testing algorithms that use NAAT alone or in combination with GDH or GDH plus toxin EIA to detect the presence of C. difficile in adults. There is insufficient evidence to recommend against repeat testing of the sample using NAAT after an initial negative result due to a lack of evidence of harm (i.e., financial, length of stay, or delay of treatment) as specified by the Laboratory Medicine Best Practices (LMBP) systematic review method in making such an assessment. Findings from this systematic review provide clarity to diagnostic testing strategies and highlight gaps, such as low numbers of GDH/toxin/PCR studies, in existing evidence on diagnostic performance, which can be used to guide future clinical research studies.

Effectiveness of Preanalytic Practices on Contamination and Diagnostic Accuracy of Urine Cultures: a Laboratory Medicine Best Practices Systematic Review and Meta-analysis.

BACKGROUND: Urinary tract infection (UTI) in the United States is the most common bacterial infection, and urine cultures often make up the largest portion of workload for a hospital-based microbiology laboratory. Appropriately managing the factors affecting the preanalytic phase of urine culture contributes significantly to the generation of meaningful culture results that ultimately affect patient diagnosis and management. Urine culture contamination can be reduced with proper techniques for urine collection, preservation, storage, and transport, the major factors affecting the preanalytic phase of urine culture. OBJECTIVES: The purposes of this review were to identify and evaluate preanalytic practices associated with urine specimens and to assess their impact on the accuracy of urine culture microbiology. Specific practices included collection methods for men, women, and children; preservation of urine samples in boric acid solutions; and the effect of refrigeration on stored urine. Practice efficacy and effectiveness were measured by two parameters: reduction of urine culture contamination and increased accuracy of patient diagnosis. The CDC Laboratory Medicine Best Practices (LMBP) initiative's systematic review method for assessment of quality improvement (QI) practices was employed. Results were then translated into evidence-based practice guidelines. SEARCH STRATEGY: A search of three electronic bibliographic databases (PubMed, SCOPUS, and CINAHL), as well as hand searching of bibliographies from relevant information sources, for English-language articles published between 1965 and 2014 was conducted. SELECTION CRITERIA: The search contained the following medical subject headings and key text words: urinary tract infections, UTI, urine/analysis, urine/microbiology, urinalysis, specimen handling, preservation, biological, preservation, boric acid, boric acid/borate, refrigeration, storage, time factors, transportation, transport time, time delay, time factor, timing, urine specimen collection, catheters, indwelling, urinary reservoirs, continent, urinary catheterization, intermittent urethral catheterization, clean voided, midstream, Foley, suprapubic, bacteriological techniques, and microbiological techniques. MAIN RESULTS: Both boric acid and refrigeration adequately preserved urine specimens prior to their processing for up to 24 h. Urine held at room temperature for more than 4 h showed overgrowth of both clinically significant and contaminating microorganisms. The overall strength of this body of evidence, however, was rated as low. For urine specimens collected from women, there was no difference in rates of contamination for midstream urine specimens collected with or without cleansing. The overall strength of this evidence was rated as high. The levels of diagnostic accuracy of midstream urine collection with or without cleansing were similar, although the overall strength of this evidence was rated as low. For urine specimens collected from men, there was a reduction in contamination in favor of midstream clean-catch over first-void specimen collection. The strength of this evidence was rated as high. Only one study compared midstream collection with cleansing to midstream collection without cleansing. Results showed no difference in contamination between the two methods of collection. However, imprecision was due largely to the small event size. The diagnostic accuracy of midstream urine collection from men compared to straight catheterization or suprapubic aspiration was high. However, the overall strength of this body of evidence was rated as low. For urine specimens collected from children and infants, the evidence comparing contamination rates for midstream urine collection with cleansing, midstream collection without cleansing, sterile urine bag collection, and diaper collection pointed to larger reductions in the odds of contamination in favor of midstream collection with cleansing over the other methods of collection. This body of evidence was rated as high. The accuracy of diagnosis of urinary tract infection from midstream clean-catch urine specimens, sterile urine bag specimens, or diaper specimens compared to straight catheterization or suprapubic aspiration was varied. AUTHORS' CONCLUSIONS: No recommendation for or against is made for delayed processing of urine stored at room temperature, refrigerated, or preserved in boric acid. This does not preclude the use of refrigeration or chemical preservatives in clinical practice. It does indicate, however, that more systematic studies evaluating the utility of these measures are needed. If noninvasive collection is being considered for women, midstream collection with cleansing is recommended, but no recommendation for or against is made for midstream collection without cleansing. If noninvasive collection is being considered for men, midstream collection with cleansing is recommended and collection of first-void urine is not recommended. No recommendation for or against is made for collection of midstream urine without cleansing. If noninvasive collection is being considered for children, midstream collection with cleansing is recommended and collection in sterile urine bags, from diapers, or midstream without cleansing is not recommended. Whether midstream collection with cleansing can be routinely used in place of catheterization or suprapubic aspiration is unclear. The data suggest that midstream collection with cleansing is accurate for the diagnosis of urinary tract infections in infants and children and has higher average accuracy than sterile urine bag collection (data for diaper collection were lacking); however, the overall strength of evidence was low, as multivariate modeling could not be performed, and thus no recommendation for or against can be made.

Quantitative cultures of bronchoscopically obtained specimens should be performed for optimal management of ventilator-associated pneumonia.

Ventilator-associated pneumonia (VAP) is a leading cause of health care-associated infection. It has a high rate of attributed mortality, and this mortality is increased in patients who do not receive appropriate empirical antimicrobial therapy. As a result of the overuse of broad-spectrum antimicrobials such as the carbapenems, strains of Acinetobacter, Enterobacteriaceae, and Pseudomonas aeruginosa susceptible only to polymyxins and tigecycline have emerged as important causes of VAP. The need to accurately diagnose VAP so that appropriate discontinuation or de-escalation of antimicrobial therapy can be initiated to reduce this antimicrobial pressure is essential. Practice guidelines for the diagnosis of VAP advocate the use of bronchoalveolar lavage (BAL) fluid obtained either bronchoscopically or by the use of a catheter passed through the endotracheal tube. The CDC recommends that quantitative cultures be performed on these specimens, using ≥ 10(4) CFU/ml to designate a positive culture (http://www.cdc.gov/nhsn/TOC_PSCManual.html, accessed 30 October 2012). However, there is no consensus in the clinical microbiology community as to whether these specimens should be cultured quantitatively, using the aforementioned designated bacterial cell count to designate infection, or by a semiquantitative approach. We have asked Vickie Baselski, University of Tennessee Health Science Center, who was the lead author on one of the seminal papers on quantitative BAL fluid culture, to explain why she believes that quantitative BAL fluid cultures are the optimal strategy for VAP diagnosis. We have Stacey Klutts, University of Iowa, to advocate the semiquantitative approach.

Lingual leishmaniasis complicating visceral disease.

Leishmania species are obligate intracellular parasites transmitted by various types of female sand flies. The clinical syndrome that results depends on a number of factors including the Leishmania species and immune response of the host. Here, we report successful treatment of lingual leishmaniasis complicating visceral disease in an immunocompetent patient.

Recommendations for diagnosis of shiga toxin--producing Escherichia coli infections by clinical laboratories.

Shiga toxin--producing Escherichia coli (STEC) are a leading cause of bacterial enteric infections in the United States. Prompt, accurate diagnosis of STEC infection is important because appropriate treatment early in the course of infection might decrease the risk for serious complications such as renal damage and improve overall patient outcome. In addition, prompt laboratory identification of STEC strains is essential for detecting new and emerging serotypes, for effective and timely outbreak responses and control measures, and for monitoring trends in disease epidemiology. Guidelines for laboratory identification of STEC infections by clinical laboratories were published in 2006. This report provides comprehensive and detailed recommendations for STEC testing by clinical laboratories, including the recommendation that all stools submitted for routine testing from patients with acute community-acquired diarrhea (regardless of patient age, season of the year, or presence or absence of blood in the stool) be simultaneously cultured for E. coli O157:H7 (O157 STEC) and tested with an assay that detects Shiga toxins to detect non-O157 STEC. The report also includes detailed procedures for specimen selection, handling, and transport; a review of culture and nonculture tests for STEC detection; and clinical considerations and recommendations for management of patients with STEC infection. Improving the diagnostic accuracy of STEC infection by clinical laboratories should ensure prompt diagnosis and treatment of these infections in patients and increase detection of STEC outbreaks in the community.

Pustular blastomycosis.

Blastomycosis is an infection caused by the dimorphic fungus Blastomyces dermatitidis. Infection can disseminate to skin, where characteristic ulcerative and verrucous plaques, sometimes studded with pustules, are typically seen. Herein we report 3 patients, two children and one adult, with pustular blastomycosis. Their cutaneous lesions exhibited a pustular morphology at the onset and throughout the course of their illness, without evolution to more typical verrucous or ulcerative plaques. These patients all resided in Memphis, TN, the site of previous case reports of pustular blastomycosis.