Background. The optimal therapy for critically ill patients with Clostridium difficile infection (CDI) is not known. We aimed to evaluate mortality among critically ill patients with CDI who received oral vancomycin (monotherapy) vs oral vancomycin with intravenous (IV) metronidazole (combination therapy). Methods. A single-center, retrospective, observational, comparative study was performed. Patients with a positive C. difficile assay who received oral vancomycin while bedded in an intensive care unit (ICU) between June 2007 and September 2012 were evaluated. Patients meeting ≥3 of the following criteria were included: albumin 90 bpm, mean arterial pressure 60 years, serum creatinine ≥1.5 times baseline, or temperature ≥100.4°F. Patients in the combination therapy group received IV metronidazole within 48 hours after initiating vancomycin. Patients <18 years or with unrelated gastrointestinal disease were excluded. The primary outcome was in-hospital mortality. Patients were matched using Acute Physiology and Chronic Health Evaluation II scores. Results. Eighty-eight patients were included, 44 in each group. Patient characteristics were similar although more patients in the combination group had renal disease. Mortality was 36.4% and 15.9% in the monotherapy and combination therapy groups, respectively (P = .03). Secondary outcomes of clinical success, length of stay, and length of ICU stay did not differ between groups. Conclusions. Our data are supportive of the use of combination therapy with oral vancomycin and IV metronidazole in critically ill patients with CDI. However, prospective, randomized studies are required to define optimal treatment regimens in this limited population of CDI patients.

Estimates of the case hospitalization rate and case fatality rate when hospital care is available for monkeypox (MPX) infections have not been well defined. This rapid systematic review and meta-analysis aimed to estimate the case hospitalisation rate and case fatality rate where hospital care is available. We systematically searched PubMed, Embase, the Lancet Preprints, and MedRxiv for studies published between Jan 1, 1950 and Aug 2, 2022. We included documents which contained both the number of cases and associated hospitalisations of MPX infections. From eligible studies we extracted the country, the year of the study, the study design type, the clade of MPX, the participant characteristics, transmission type, any treatments used, number of cases (including suspected, probable, or laboratory confirmed diagnosis), number of hospitalizations, hospitalized patient outcomes, and case definition. Case hospitalization rate (CHR) was defined as the proportion of cases that were admitted to hospital care while case fatality rate (CFR) was defined as the proportion of cases that died. CHR and CFR were analysed in a fully Bayesian meta-analytic framework using random effects models, including sub-group analysis with heterogeneity assessed using I². Of the 259 unique documents identified, 19 studies were eligible for inclusion. Included studies represented 7553 reported cases among which there were 555 hospitalizations. Of the 7540 cases for which outcomes were available, there were 15 recorded deaths. The median age of cases was 35 years (interquartile range 28–38, n = 2010) and primarily male (7339/7489, 98%) in studies where age or sex were available. Combined CHR was estimated to be 14.1% (95% credible interval, 7.5–25.0, I² 97.4%), with a high degree of heterogeneity. Further analysis by outbreak period indicates CHRs of 49.8% (28.2–74.0, I² 81.4%), 21.7% (7.2–52.1, I² 57.7%), and 5.8% (3.2–9.4, I² 92.4%) during the pre-2017, 2017–2021, and 2022 outbreaks, respectively, again with high levels of heterogeneity. CFR was estimated to be 0.03% (0.0–0.44, I² 99.9%), with evidence of large heterogeneity between the studies. There is limited data for MPX hospitalization rates in countries where MPX has been traditionally non-endemic until the current outbreak. Due to substantial heterogeneity, caution is needed when interpreting these findings. Health care organizations should be cognizant of the potential increase in healthcare utilization. Rapid identification of infection and use of appropriate therapies such as antivirals play a role reducing the CHR and associated CFR. None.

Expanding antimicrobial resistance patterns in the face of stagnant growth in novel antibiotic production underscores the importance of antibiotic stewardship in which de-escalation remains an integral component. We measured the frequency of antibiotic de-escalation in a tertiary care medical center with an established antimicrobial stewardship program to provide a plausible benchmark for de-escalation. A retrospective, observational study was performed by review of randomly selected electronic medical records of 240 patients who received simultaneous piperacillin/tazobactam and vancomycin from January to December 2011 at an 885-bed tertiary care medical center. Patient characteristics including antibiotic regimen, duration and indication, culture results, length of stay, and hospital mortality were evaluated. Antibiotic de-escalation was defined as the use of narrower spectrum antibiotics or the discontinuation of antibiotics after initiation of piperacillin/tazobactam and vancomycin therapy. Subjects dying within 72 h of antibiotic initiation were considered not de-escalated for subsequent analysis and were subtracted from the study population in determining a modified mortality rate. The most commonly documented indications for piperacillin/tazobactam and vancomycin therapy were pneumonia and sepsis. Of the 240 patients studied, 151 (63%) had their antibiotic regimens de-escalated by 72 h. The proportion of patients de-escalated by 96 h with positive vs. negative cultures was similar, 71 and 72%, respectively. Median length of stay was 4 days shorter in de-escalated patients, and the difference in adjusted mortality was not significant (p = 0.82). The empiric antibiotic regimens of approximately two-thirds of patients were de-escalated by 72 h in an institution with a well-established antimicrobial stewardship program. While this study provides one plausible benchmark for antibiotic de-escalation, further studies, including evaluations of antibiotic appropriateness and patient outcomes, are needed to inform decisions on potential benchmarks for antibiotic de-escalation.

Background: Extended infusion (EI) dosing provides a longer time above the minimum inhibitory concentration, which is important for the clinical success of β-lactam antibiotics, especially for patients with impaired immunity. The aim of this study was to determine the feasibility and clinical impact of administering cefepime by EI as treatment of febrile neutropenia. Methods: This was a prospective, randomized, comparative pilot study. All patients received cefepime 2 g IV every 8 h, with the first dose administered using a 30-min infusion. After the first dose, patients were randomized to receive cefepime over 30 min as a standard infusion (SI) or 3 h (EI). Patients were >18 years old with febrile neutropenia (neutrophil count 38.0ºC) and received chemotherapy or stem cell transplant as treatment for malignancy. Patients were excluded for the following: allergy to a cephalosporin, creatinine clearance (CrCl) < 50 mL/min, receipt of concurrent Gram-negative antimicrobial, sepsis, or solid tumor malignancy. The primary outcome was defervescence by 72 h. Secondary outcomes included time to defervescence, clinical success, in-hospital mortality, hospital length of stay, and need for additional antimicrobials. Main results: Sixty-three patients were enrolled: 33 in the SI arm and 30 in the EI arm. The groups were similar with regard to age, gender, weight, estimated creatinine clearance, and duration of neutropenia. None of the patients in the EI arm withdrew due to practical complications of receiving EI cefepime. Twenty-three patients in the SI arm and 20 patients in the EI arm defervesced by 72 h ( p = 0.99). There were no differences in secondary outcome measures; however, patients in the EI arm appeared to have defervesced more rapidly (median 19 vs. 41 h, p = 0.305). Conclusion: Administration of cefepime by EI for the treatment of febrile neutropenia is feasible. Larger clinical trials are necessary to determine if EI cefepime imparts a clinical benefit in the treatment of febrile neutropenia.