Propensity Score and Desirability of Outcome Ranking Analysis of Ertapenem for Treatment of Nonsevere Bacteremic Urinary Tract Infections Due to Extended-Spectrum-Beta-Lactamase-Producing Enterobacterales in Kidney Transplant Recipients.

There are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with nonsevere bacteremic urinary tract infections (B-UTI) caused by ESBL-E. We performed a registered, retrospective, international (29 centers in 14 countries) cohort study (INCREMENT-SOT, NCT02852902). The association between targeted therapy with ertapenem versus meropenem and clinical cure at day 14 (the principal outcome) was studied by logistic regression. Propensity score matching and desirability of outcome ranking (DOOR) analyses were also performed. A total of 201 patients were included; only 1 patient (treated with meropenem) in the cohort died. Clinical cure at day 14 was reached in 45/100 (45%) and 51/101 (50.5%) of patients treated with ertapenem and meropenem, respectively (adjusted OR 1.29; 95% CI 0.51 to 3.22; P = 0.76); the propensity score-matched cohort included 55 pairs (adjusted OR for clinical cure at day 14, 1.18; 95% CI 0.43 to 3.29; P = 0.74). In this cohort, the proportion of cases treated with ertapenem with better DOOR than with meropenem was 49.7% (95% CI, 40.4 to 59.1%) when hospital stay was considered. It ranged from 59 to 67% in different scenarios of a modified (weights-based) DOOR sensitivity analysis when potential ecological advantage or cost was considered in addition to outcome. In conclusion, targeted therapy with ertapenem appears as effective as meropenem to treat nonsevere B-UTI due to ESBL-E in KT recipients and may have some advantages.

Efficacy of ß-lactam/ß-lactamase inhibitors to treat extended-spectrum beta-lactamase-producing Enterobacterales bacteremia secondary to urinary tract infection in kidney transplant recipients (INCREMENT-SOT Project).

BACKGROUND: Whether active therapy with ß-lactam/ß-lactamase inhibitors (BLBLI) is as affective as carbapenems for extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) bloodstream infection (BSI) secondary to urinary tract infection (UTI) in kidney transplant recipients (KTRs) remains unclear. METHODS: We retrospectively evaluated 306 KTR admitted to 30 centers from January 2014 to October 2016. Therapeutic failure (lack of cure or clinical improvement and/or death from any cause) at days 7 and 30 from ESBL-E BSI onset was the primary and secondary study outcomes, respectively. RESULTS: Therapeutic failure at days 7 and 30 occurred in 8.2% (25/306) and 13.4% (41/306) of patients. Hospital-acquired BSI (adjusted OR [aOR]: 4.10; 95% confidence interval [CI]: 1.50-11.20) and Pitt score (aOR: 1.47; 95% CI: 1.21-1.77) were independently associated with therapeutic failure at day 7. Age-adjusted Charlson Index (aOR: 1.25; 95% CI: 1.05-1.48), Pitt score (aOR: 1.72; 95% CI: 1.35-2.17), and lymphocyte count ≤500 cells/µL at presentation (aOR: 3.16; 95% CI: 1.42-7.06) predicted therapeutic failure at day 30. Carbapenem monotherapy (68.6%, primarily meropenem) was the most frequent active therapy, followed by BLBLI monotherapy (10.8%, mostly piperacillin-tazobactam). Propensity score (PS)-adjusted models revealed no significant impact of the choice of active therapy (carbapenem-containing vs any other regimen, BLBLI- vs carbapenem-based monotherapy) within the first 72 hours on any of the study outcomes. CONCLUSIONS: Our data suggest that active therapy based on BLBLI may be as effective as carbapenem-containing regimens for ESBL-E BSI secondary to UTI in the specific population of KTR. Potential residual confounding and unpowered sample size cannot be excluded (ClinicalTrials.gov identifier: NCT02852902).

Prescribing antibiotics in diabetic foot infection: what is the role of initial microscopy and culture of tissue samples?

The aim of this study was to evaluate the role of microscopy, Gram stain and the culture of tissue samples in the antibiotic treatment of patients with diabetic foot infection. A retrospective review of patients with a diabetic foot infection was undertaken. Data analysed included the severity of infection, antibiotic prescribing patterns, microscopy and culture results. A total of 71 patients were included, from whom 114 tissue samples were collected. Gram stain results were in agreement with final culture results in 45·8% (n = 54) of samples. Overall sensitivity and specificity of the Gram stains were low (74·5% and 69·8%, respectively), although the specificity for Gram-negative rods was high (98·5%). The presence or absence of 'pus cells' on microscopy was a poor predictor of culture results. Empirical prescribing of antibiotics was in accordance with local policy in 31·1% of patients, improving to 86·8 % following culture results. Microscopy, a skilled laboratory procedure, was generally a poor predictor of tissue culture results. However, the presence of Gram-negative rods was suggestive of isolation in the culture of such organisms and could allow the early broadening of antibiotic treatment. Despite initial poor compliance of empirical antibiotic treatment regimens, prescribing was adjusted in light of culture results, suggesting these were important for clinicians.

Emergence of linezolid resistance in hepatobiliary infections caused by Enterococcus faecium.

Enterococcal infections are common in liver transplantation and hepatopancreaticobiliary (HPB) surgery. Linezolid is frequently used to treat not only vancomycin-resistant Enterococcus (VRE), but also vancomycin-sensitive Enterococcus (VSE) infections, and resistance can develop. This study evaluated all the Liver Unit patients who developed infections with linezolid-resistant Enterococcus (LRE) in order to elicit the association with prior linezolid usage, to explore possible risk factors for infection, and to better understand the epidemiology of these isolates in this patient group. Between 2010 and 2015, infections with LRE developed in 10 patients (8 following liver transplantation and 2 following HPB surgery) after 22-108 days of treatment. Selected pulsed-field gel electrophoresis demonstrated that 2 out of 10 patients were cocolonized with different strains and indicated that cross-transmission may have occurred. In conclusion, in this group of patients with complex hepatobiliary infections, the optimal antibiotic strategies for the treatment of Enterococcus faecium infections are not clearly defined, and there is a significant risk of emergence of resistance to linezolid in E. faecium after exposure to this agent in patients, especially in the presence of a deep source of infection on a background of hepatic artery insufficiency. Caution is needed when using prolonged courses of linezolid in this setting, and further studies are necessary to determine the optimum treatment.

Staphylococcus aureus bacteraemia in a UK tertiary referral centre: a 'transoesophageal echocardiogram for all' policy.

OBJECTIVES: Infective endocarditis (IE) is a feared complication in up to 38% of cases of Staphylococcus aureus bacteraemia (SAB). BSAC guidelines recommend echocardiography in all cases of SAB. The aim of this study was to determine the incidence of IE in SAB using transoesophageal echocardiography (TOE) as the first step in diagnostic imaging. This study also sought to identify clinical predictors that could improve stratification of those with and without IE. METHODS: A guideline was implemented that any SAB resulted in the microbiology department (i) recommending that the patient be referred for TOE and (ii) notifying the echocardiography department, resulting in streamlined listing of the patient for TOE. All cases of SAB were then assessed prospectively at University Hospitals Birmingham NHS Foundation Trust between September 2011 and October 2012. Previously identified risk factors for complicated S. aureus bacteraemia were recorded. RESULTS: There were 98 SAB episodes in total. TOE was performed in 58 (59%) with a further 22 episodes imaged by transthoracic echocardiography alone. IE was diagnosed overall in 13 (16%) cases investigated with echocardiography. No risk factor for IE other than presence of a cardiac device was detected in this group (P = 0.013). CONCLUSIONS: The rate of IE found in SAB is high when TOE is performed first line. There are no clear risk factors to improve yield or the type of echocardiography to be performed. Echocardiography should be performed in all cases and TOE should be considered where it is expected to influence management, as long as local resources allow.

Genomic Assembly of Clinical Candida glabrata (Nakaseomyces glabrata) Isolates Reveals within-Species Structural Plasticity and Association with In Vitro Antifungal Susceptibility.

The opportunistic human pathogen Candida glabrata has become an increasingly important threat to human health, with infections globally characterized by high mortality rates and multidrug resistance. To face this threat, more efficient diagnostic and therapeutic approaches are required, underpinning research to help define the intraspecies epidemiology, genetic variability, and therefore, diagnostic and therapeutic target stability. Previous comparative genetics studies conducted on limited numbers of strains only revealed partial resolution of chromosomal settings. In this study, by combining short- and long-read genome sequencing, phenotypic characterization, and comparative genomics over a large set of strains, we detected strict relationships between large chromosomal rearrangements and phylogenetic clades, genes subjected to different selective pressures, and new sets of genes associated with resistance to antifungals. Overall, these results not only provide a fundamental contribution to our knowledge of C. glabrata evolution and epidemiology but may also lay the foundations for the future development of tailored therapeutic approaches. IMPORTANCE The human pathogen Candida glabrata has become a global threat to human health, with infections characterized by high mortality and multidrug resistance. We have obtained nine fully assembled genomes from clinical isolates through a combination of short- and long-read sequencing approaches. The quality and completeness of such genomes and their subsequent comparison to the broadest set of genomes so far allowed us to pinpoint chromosomal rearrangements in several genomes and detect phylogenetic clades that were not associated with geographic location or isolation source. We identified a new set of genes associated with resistance to antifungals coding for adhesin or adhesin-like proteins, suggesting C. glabrata resists antifungals by forming aggregates or adhering to the host tissue. These results, which provide a fundamental contribution to our knowledge of C. glabrata evolution and epidemiology, may initiate the development of precision medicine interventions for patients with suspected or proven invasive fungal infections.

Retransplantation in Late Hepatic Artery Thrombosis: Graft Access and Transplant Outcome.

BACKGROUND: Definitive treatment for late hepatic artery thrombosis (L-HAT) is retransplantation (re-LT); however, the L-HAT-associated disease burden is poorly represented in allocation models. METHODS: Graft access and transplant outcome of the re-LT experience between 2005 and 2016 was reviewed with specific focus on the L-HAT cohort in this single-center retrospective study. RESULTS: Ninety-nine (5.7%) of 1725 liver transplantations were re-LT with HAT as the main indication (n = 43; 43%) distributed into early (n = 25) and late (n = 18) episodes. Model for end-stage liver disease as well as United Kingdom model for end-stage liver disease did not accurately reflect high disease burden of graft failure associated infections such as hepatic abscesses and biliary sepsis in L-HAT. Hence, re-LT candidates with L-HAT received low prioritization and waited longest until the allocation of an acceptable graft (median, 103 days; interquartile range, 28-291 days), allowing for progression of biliary sepsis. Balance of risk score and 3-month mortality score prognosticated good transplant outcome in L-HAT but, contrary to the prediction, the factual 1-year patient survival after re-LT was significantly inferior in L-HAT compared to early HAT, early non-HAT and late non-HAT (65% vs 82%, 92% and 95%) which was mainly caused by sepsis and multiorgan failure driving 3-month mortality (28% vs 11%, 16% and 0%). Access to a second graft after a median waitlist time of 6 weeks achieved the best short- and long-term outcome in re-LT for L-HAT (3-month mortality, 13%; 1-year survival, 77%). CONCLUSIONS: Inequity in graft access and peritransplant sepsis are fundamental obstacles for successful re-LT in L-HAT. Offering a graft for those in need at the best window of opportunity could facilitate earlier engrafting with improved outcomes.

Diagnosing Tuberculous Peritonitis Early in Patients on Peritoneal Dialysis: Use of Xpert MTB/RIF Assay.

Diagnosing tuberculous peritonitis can be challenging, with mycobacterial culture potentially taking weeks for a positive result. This report describes 2 cases where a prompt diagnosis of tuberculous peritonitis was made employing the Xpert MTB/RIF assay (Cepheid Inc., Sunnyvale, CA, USA).