Machine-learning-based risk assessment tool to rule out empirical use of ESBL-targeted therapy in endemic areas.

BACKGROUND: Antimicrobial stewardship focuses on identifying patients who require extended-spectrum beta-lactamase (ESBL)-targeted therapy. 'Rule-in' tools have been researched extensively in areas of low endemicity; however, such tools are inadequate for areas with high prevalence of ESBL-producing pathogens, as almost all patients will be selected. AIM: To develop a machine-learning-based 'rule-out' tool suitable for areas with high levels of resistance. METHODS: Gradient-boosted decision trees were used to train and validate a risk prediction model on data from 17,913 (45% ESBL) patients with Escherichia coli and Klebsiella pneumoniae in urine cultures. The predictive power of different sets of variables was evaluated using Shapley values to evaluate the contributions of variables. FINDINGS: The model successfully identified patients with low risk of ESBL resistance in ESBL-endemic areas (area under receiver operating characteristic curve 0.72). When used to select the 30% of patients with the lowest predicted risk, the model yielded a negative predictive value ≥0.74. A simplified model with seven input features was found to perform nearly as well as the full model. This simplified model is freely accessible as a web application. CONCLUSIONS: This study found that a risk calculator for antibiotic resistance can be a viable 'rule-out' strategy to reduce the use of ESBL-targeted therapy in ESBL-endemic areas. The robust performance of a version of the model with limited features makes the clinical use of such a tool feasible. This tool provides an important alternative in an era with growing rates of ESBL-producing pathogens, where some experts have called for empirical use of carbapenems as first-line therapy for all patients in areas with high prevalence of ESBL-producing pathogens.

SARS-CoV-2 universal screening upon adult hospital admission in Southern Israel.

As the prevalence of coronavirus disease 2019 (COVID-19) increased in the local community, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) universal screening was initiated for all adult patients admitted through the emergency departments (EDs) at Soroka University Medical Centre. Of 8518 patients screened, 288 (3.38%) tested positive. One hundred and thirty-three (46%) positive cases were asymptomatic and would have been admitted without necessary precautions. Patients with symptoms that may be attributable to COVID-19 were significantly older and were admitted through the medical ED. Patients of Bedouin Arab ethnicity accounted for half of those who tested positive, which was double their prevalence in the general population. These findings indicate that universal SARS-CoV-2 screening on adult hospital admission is crucial in areas with a high prevalence of COVID-19.

Outcomes of UTI and bacteriuria caused by ESBL vs. non-ESBL Enterobacteriaceae isolates in pregnancy: a matched case-control study.

Infections caused by extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) have become increasingly prevalent, posing a serious public threat worldwide. It is commonly believed that untreated urinary tract infections (UTI) and asymptomatic bacteriuria (ABU) during pregnancy are associated with poor obstetric outcomes. Currently, there is a paucity of data regarding the outcomes or risk factors of such ESBL-E infections in pregnant women. We conducted a retrospective 1:2 matched case-control study of hospitalised pregnant women with ESBL-E- vs. non-ESBL-producing Enterobacteriaceae-positive urine cultures obtained between 2004 and 2015, and compared risk factors for the development of resistant bacteria, clinical course and outcomes. In total, 87 pregnant women with ESBL-E-positive urine cultures were matched to 174 controls by decade of age, ethnicity and pregnancy trimester. Significant risk factors for acquisition of ESBL-E included prior UTI/ABU episodes (50.6% vs. 26.3%, P < 0.001), previous isolation of ESBL-E in urine cultures (12.6% vs. 0.6%, P < 0.001) and prior antibiotic exposure (71.3% vs. 54%, P = 0.002). Previous hospitalisation, however, was not found to be a risk factor. No significant difference was found in adverse obstetric outcomes. We conclude that prior urinary infections and antibiotic exposure were significant risk factors for the isolation of ESBL-E pathogens from the urine of pregnant women; however, this was not associated with worse obstetric outcomes compared with non-ESBL-E pathogens.

Epidemiology of meningitis with a negative CSF Gram stain: under-utilization of available diagnostic tests.

Meningitis with a negative cerebrospinal fluid Gram stain (CSF-GS) poses a diagnostic challenge as more than 50% of patients remain without an aetiology. The introduction of polymerase chain reaction (PCR) and arboviral serologies have increased diagnostic capabilities, yet large scale epidemiological studies evaluating their use in clinical practice are lacking. We conducted a prospective observational study in New Orleans between November 1999 and September 2008 (early era) when PCR was not widely available, and in Houston between November 2008 and June 2013 (modern era), when PCR was commonly used. Patients presenting with meningitis and negative CSF-GS were followed for 4 weeks. All investigations, PCR used, and results were recorded as they became available. In 323 patients enrolled, PCR provided the highest diagnostic yield (24·2%) but was ordered for 128 (39·6%) patients; followed by serology for arboviruses (15%) that was ordered for 100 (31%) of all patients. The yield of blood cultures was (10·3%) and that of CSF cultures was 4%; the yield for all other tests was <10%. Overall, 65% of the patients remained without a diagnosis at 4 weeks: 72·1% in early era vs. 53·4% (P < 0·01) in modern era; this change was attributed to diagnosing more viral pathogens, 8·3% and 26·3% (P < 0·01), respectively. The introduction of PCR and arboviral serologies has improved the yield of diagnosing patients with meningitis and a negative CSF-GS, but both tests are being under-utilized.

Ertapenem usage in cancer patients with and without neutropenia: a report on 97 cases from a comprehensive cancer center.

PURPOSE: Ertapenem is being increasingly utilized in cancer patients, but published data regarding its usage are limited. Our objective was to describe the various indications for ertapenem therapy and its safety and efficacy in cancer patients. METHODS: We conducted a retrospective cohort study of cancer patients who received monotherapy with ertapenem for at least 72 h, between January 2007 and February 2013. RESULTS: Among 97 unique patients who received ertapenem monotherapy, the most common indications were: (1) To facilitate discharge from the hospital of stable patients still requiring antimicrobial therapy (46 %). (2) Primary therapy of various documented infections (bacteremia, pneumonia, urinary tract infection, skin and skin structure infection) with ertapenem (28 %). (3) De-escalation from a different broad-spectrum agent or regimen to ertapenem within the hospital setting in patients not ready for discharge (25 %). The median age of the 97 patients studied was 59 years (range 9-87 years) with 52 % being men. Most patients had underlying hematologic malignancies (54 %), and 7 % were recipients of hematopoietic stem cell transplantation. Twenty-nine patients (30 %) were neutropenic, 26 % were diabetic, and 6 % had chronic lung disease. Primary ertapenem monotherapy was successful in all patients, de-escalation in 95.8 % of patients, and the strategy of discharge on outpatient therapy with ertapenem in 95.6 % of patients. Patients failing de-escalation or early discharge responded to alternative regimens. We documented no significant ertapenem associated toxicity or adverse events. CONCLUSIONS: Ertapenem appears to be safe and effective for several indications in cancer patients.

Fecal colonization and infection with Pseudomonas aeruginosa in recipients of allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Pseudomonas aeruginosa, especially multidrug-resistant (MDR) isolates, is an important pathogen in allogeneic hematopoietic stem cell transplant (HCT) recipients. The ability to identify patients at risk for these infections and administer appropriate empiric therapy, particularly during episodes of neutropenia, may improve outcomes and also direct infection control and antimicrobial stewardship efforts. Many transplant centers obtain routine surveillance stool cultures (SSCs) from HCT recipients to test for colonization with vancomycin-resistant enterococci, and extended-spectrum beta lactamase-producing Enterobacteriaceae. Our center initiated the performance of SSCs for P. aeruginosa, because of a perceived increase in the frequency of infection with MDR strains. The aim of this study was to determine the utility of this practice. METHODS: We conducted a 2-year (2010-2011) retrospective review of the medical records of all patients who underwent allogeneic HCT at our cancer center to (a) determine the frequency of fecal colonization with P. aeruginosa, including MDR strains; (b) to determine the overall frequency of subsequent P. aeruginosa infection, as well as the frequency of infection with MDR strains; (c) to ascertain the proportion of subsequent infections likely arising from the intestinal tract; and (d) to determine risk factors for progression from colonization to infection. RESULTS: Of 794 study patients, 58 (7.3%) had at least 1 positive SSC for P. aeruginosa; 19/58 (32.8%) developed a subsequent pseudomonal infection (11 with matching antimicrobial resistance patterns). On the other hand, 37/736 (5%) of the patients who were not colonized, developed a pseudomonal infection. The type of infection observed was pneumonia in 26 (46%) patients, bloodstream infection in 20 (36%), urinary tract infection in 8 (14%), and infections at other sites in 2 (4%). The incidence of MDR P. aeruginosa in the entire cohort was 2.2% (18 of 794): 12 had positive SSCs and 7 of these patients later developed MDR P. aeruginosa infections. Patients with acute myelogenous leukemia were more likely to be colonized and to develop subsequent infection. No infection-related deaths were observed during the first 30 days after infection. CONCLUSIONS: The incidence of P. aeruginosa colonization and subsequent infection was low. Patients who were not colonized had a low chance of developing P. aeruginosa infection. Most patients who developed infection did not have fecal colonization, suggesting a different source of infection. SSCs for P. aeruginosa provide incomplete information regarding the source of infection.

Regional community-acquired urinary tract infections in Israel: diagnosis, pathogens, and antibiotic guidelines adherence: a prospective study.

INTRODUCTION: The identification and treatment of hospitalized patients with community-acquired urinary tract infections (CAUTI) may be a challenge. The pathogens causing the infection and their relative proportions vary geographically and with time. This observational prospective study had three primary goals: (1) to estimate the likelihood of diagnosis of CAUTI upon admission; (2) to evaluate adherence to the institutional recommendations; (3) to assess the compatibility of the current local antibiotic recommendations with a pathogen's distribution and with its drug sensitivities. METHODS AND RESULTS: Two hundred and twenty-three patients with positive urinary cultures fulfilling criteria for CAUTI were studied. Only 54 (24.2%) were diagnosed as having a urinary tract infection upon admission. Approximately 90% of the patients, who were correctly diagnosed, received the institutional recommended antibiotic therapy (ofloxacin or cefuroxime). Gram-negative intestinal flora comprised 86.1% (192 patients) of the causative microorganisms. Of these, 20.3% of the pathogens demonstrated resistance to ofloxacin and 19.8% to cefuroxime. The prevalence of Escherichia coli, the most common pathogen of UTI, significantly declined in the current study, from 70.5% in 1991 to 56% in 2000. CONCLUSIONS: We observed a low sensitivity in diagnosing community-acquired urinary tract infections upon admission. In patients correctly diagnosed, the use of recommended antibiotics was high. A substantial percentage of the pathogens were resistant to the recommended antibiotics. This study stresses the need for frequent re-evaluation of the prevalence of pathogens involved in regional community-acquired urinary tract infections and the adjustment of the empirical first-line treatment accordingly.