Doxycycline versus cephalexin treatment of presumed streptococcal skin and soft tissue infection among adults presenting to the emergency department.

Among 100 propensity score-matched emergency department patients receiving ≤14 days doxycycline versus cephalexin monotherapy for outpatient treatment of nonpurulent (presumed streptococcal) skin and soft tissue infection, a low rate of 14-day clinical failure was observed [6% each group; odds ratio (OR), 1.34 (0.21-8.69); P = 0.745], defined as hospital admission, i.v. antibiotic therapy, or change in oral antibiotic. Doxycycline may represent a reasonable therapeutic alternative for this indication in regions with low tetracycline resistance.

Evaluating the efficacy and safety of letermovir compared to valganciclovir for the prevention of human cytomegalovirus disease in adult lung transplant recipients.

BACKGROUND: Lung transplant recipients are at high risk for severe cytomegalovirus (CMV) disease. Off-label use of letermovir (LET) may avert myelotoxicity associated with valganciclovir (VGCV), but data in lung transplantation are limited. This study aims to evaluate the outcomes of LET prophylaxis among lung transplant recipients. METHODS: This retrospective, matched cohort study included lung transplant recipients who received LET for primary CMV prophylaxis following VGCV intolerance. Patients were matched 1:1 to historical VGCV controls based on age, serostatus group, and time from transplant. The primary outcome was CMV breakthrough within 1 year post-LET initiation; secondary outcomes included hematologic changes. RESULTS: A total of 124 lung transplant recipients were included per group (32% CMV mismatch, D+R-), with LET initiated a median of 9.6 months post-transplantation. One CMV breakthrough event (0.8%) was observed in the LET group versus four (3.2%) in the VGCV group (p = .370). The median (interquartile range) white blood cell (WBC) count was 3.1 (2.1-5.6) at LET initiation which increased to 5.1 (3.9-7.2) at the end of follow-up (p <.001). For VGCV controls, WBC was 4.8 (3.4-7.2) at baseline and 5.4 (3.6-7.2) at the end of follow-up; this difference was not statistically significant (p = .395). Additionally, 98.4% of LET patients experienced ≥1 leukopenia episode in the year prior to LET compared to 71.8% the year after initiation (p <.001). Similar results were observed for neutropenia (48.4% and 17.7%, p <.001). CONCLUSION: LET prophylaxis was associated with a low rate of CMV reactivation and leukopenia recovery. LET may represent a reasonable prophylaxis option for lung transplant recipients unable to tolerate VGCV.

Can fluconazole be used for inpatient re-treatment of coccidioidomycosis among patients with past fluconazole exposures?

BACKGROUND: Coccidioides spp. may cause significant disease requiring hospitalisation, but optimal antifungal therapy among inpatients following outpatient fluconazole exposures is unknown. OBJECTIVES: The objective of this study is to describe the effectiveness of fluconazole among patients hospitalised for coccidioidomycosis despite recent outpatient fluconazole treatment. PATIENTS/METHODS: Patients were admitted to an academic medical center in Phoenix, Arizona from 1 January 2013 through 31 December 2020 for coccidioidomycosis following at least 30 days of outpatient treatment and re-initiation of fluconazole upon admission. The primary outcome was the proportion of patients with an improved response per the change in the modified Mycosis Study Group (MSG) score (a composite of symptoms, serology and radiographic findings) and clinician impressions. RESULTS: Sixty-seven patients were included, with most (54%) admitted to the intensive care unit. Meningitis was the most common infectious presentation (55%), 17 patients (25%) had multiple infection sites, and 23 (34%) were culture-positive for Coccidioides. Upon admission, the median (IQR) MSG score was 11 (9-14), which dropped to 4 (1-7) at end of therapy or last follow-up. Overall, after initiation of fluconazole therapy at a median daily dose of 800 mg, 48 patients (72%) improved in overall status, 10 (15%) showed stable disease and 9 (13%) were unresponsive. Improved response rates were high across all infection sites, including meningitis (68%) and bone infection (71%). There was no significant difference in response rates between patients with and without reported outpatient fluconazole nonadherence. CONCLUSIONS: The majority of patients admitted to the hospital for coccidioidomycosis appeared responsive to fluconazole therapy despite past outpatient exposures.

Universal Lifelong Fungal Prophylaxis and Risk of Coccidioidomycosis in Lung Transplant Recipients Living in an Endemic Area.

BACKGROUND: Lung transplant recipients residing in the endemic region are vulnerable to severe morbidity and mortality from Coccidioides. As infection risk persists beyond the first posttransplant year, investigations evaluating extended prophylaxis durations are needed. The purpose of this study is to assess the incidence of coccidioidomycosis among lung transplant recipients receiving universal lifelong azole antifungal prophylaxis. METHODS: Patients receiving transplants from 2013-2018 and initiated on azole antifungal prophylaxis at a lung transplant center in Arizona were included and followed through 2019 or until death, second transplant, or loss to follow-up. Recipients who died or received treatment for coccidioidomycosis during the transplant admission, or who had received a previous transplant, were excluded. The primary outcome was proven or probable coccidioidomycosis with new asymptomatic seropositivity assessed secondarily. RESULTS: A total of 493 lung transplant recipients were included, with 82% initiated on itraconazole prophylaxis, 9.3% on voriconazole, and 8.5% on posaconazole. Mean age at transplant was 62 years, 77% were diabetic, and 8% were seropositive for Coccidioides pretransplant. After a median follow-up of 31 months, 1 proven infection and 1 case of new asymptomatic seropositivity (1/493 each, 0.2% incidence) occurred during the study period. The single coccidioidomycosis case occurred 5 years posttransplant in a patient who had azole prophylaxis stopped several months prior. Although within-class switches were common throughout the study period, permanent discontinuation of azole prophylaxis was rare (1.4% at end of follow-up). CONCLUSIONS: Universal lifelong azole prophylaxis was associated with a low rate of coccidioidomycosis among lung transplant recipients residing in endemic regions.

Nocardia prophylaxis, treatment, and outcomes of infection in lung transplant recipients: A matched case-control study.

BACKGROUND: Lung transplant recipients are at heightened risk for nocardiosis compared to other solid organ transplant recipients, with incidence rates as high as 9% and up to 30% associated mortality. No controlled studies assessing risk factors for nocardiosis in this high-risk population have been reported. METHODS: Patients undergoing lung transplantation at a single center between 2012 and 2018 and diagnosed with nocardiosis post-transplant were matched 1:2 to uninfected control subjects on the basis of age, transplant date, and sex. RESULTS: The incidence of nocardiosis in this lung transplant population was 3.4% (20/586), occurring a median of 9.4 months (range 4.4-55.2) post-transplant. In multivariable analysis, consistent use of trimethoprim/sulfamethoxazole (TMP/SMX) in the 12 weeks prior to diagnosis was independently associated with protection against nocardiosis (OR 0.038; 95% CI 0.01-0.29; P = .002). Augmented immunosuppression in the 6 months prior to diagnosis was independently associated with the development of nocardiosis (OR 9.94; 95% CI 1.62- 61.00; P = .013). Six case patients (30%) had disseminated disease; all-cause 6-month mortality was 25%. The most common species was Nocardia farcinica (7/17 isolates), which was associated with dissemination and mortality. The most active antibiotics were TMP/SMX (100%), linezolid (100%), and amikacin (76%). Imipenem was only active against 4/17 isolates (24% susceptibility), with two isolates becoming non-susceptible later in therapy. CONCLUSIONS: Trimethoprim/sulfamethoxazole prophylaxis was shown to be protective against nocardiosis in lung transplant recipients, while augmented immunosuppression conferred increased risk. Institutional epidemiologic data are needed to best guide empiric therapy for Nocardia, as historical in vitro data may not predict local susceptibilities.

COVID-19 in a lung transplant recipient: Exploring the diagnostic role of circulating exosomes and the clinical impact of advanced immunosuppression.

Exosomes isolated from plasma of lung transplant recipients with allograft injury contain donor-derived lung self-antigens (collagen V and Kα1 tubulin) and human leukocyte antigen (HLA) molecules. We present a case of a 76-year-old, female lung transplant recipient treated for acute cellular rejection with methylprednisolone and anti-thymocyte globulin, who subsequently contracted SARS-CoV-2 and developed a sharp increase in the mean fluorescent intensity of anti-HLA antibodies. Analysis of circulating exosomes during rejection, but before SARS-CoV-2 infection, revealed the presence of lung self-antigens and HLA class II molecules. After the patient contracted SARS-CoV-2, exosomes with the SARS-CoV-2 spike protein were also found. After resolution of infectious symptoms, exosomes with SARS-CoV-2 spike protein were no longer detected; however, exosomes with lung self-antigens and HLA class II molecules persisted, which coincided with a progressive decline in spirometric flows, suggesting chronic lung allograft dysfunction. We propose that the analysis of circulating exosomes may be used to detect allograft injury mediated by both rejection and infection. Furthermore, the detection of exosomes containing viral proteins may be helpful in identifying allograft injury driven by viral pathogens.

A Systematic Review of Single-Dose Aminoglycoside Therapy for Urinary Tract Infection: Is It Time To Resurrect an Old Strategy?

Increasing bacterial resistance and poor patient adherence rates limit the effectiveness of conventional antibiotic therapies for urinary tract infection (UTI). The objective of this study was to investigate whether a single aminoglycoside dose adequately treated UTI. A systematic search of PubMed/MEDLINE and Google Scholar databases was performed through September 2018 for English language original research articles assessing the efficacy of one-time parenteral aminoglycoside as UTI monotherapy. Of 252 potentially relevant studies, 13 studies met the inclusion criteria, representing 13,804 patients. Patient ages ranged from 2 weeks to >70 years; both inpatient and outpatient settings were represented. Cystitis was more common than pyelonephritis, and more females were represented than males. Escherichia coli was the most commonly isolated uropathogen. The pooled microbiologic cure rate with single-dose aminoglycoside therapy was 94.5% ± 4.3%. Cure was sustained (no recurrence) for 73.4% ± 9.6% of patients at day 30. Lower cure rates were observed among patients with radiographic urinary tract abnormality (chi-square P < 0.01). Across all studies, 63/13,804 (0.5%) cases of nephrotoxicity, vestibular toxicity, or injection site reaction were reported; no hearing loss was observed. Single-dose aminoglycoside therapy appears to be an effective treatment option for lower UTI in nonseptic patients, with minimal toxicity. Additional studies would be beneficial to confirm efficacy for pyelonephritis. When resistance to first-line UTI agents is endemic, aminoglycosides may serve as ß-lactam- and fluoroquinolone-sparing options.

Pharmacotherapy-Induced Hepatitis B Reactivation Among Patients With Prior Functional Cure: A Systematic Review.

OBJECTIVE: To describe and quantify the incidence and morbidity of hepatitis B reactivation (HBVr) secondary to pharmaceutical agents (eg, rituximab, tumor necrosis factor inhibitors, direct-acting antivirals [DAAs] for hepatitis C) among patients with previously resolved hepatitis B infection. DATA SOURCES: The MEDLINE database was searched from inception through July 2018 using the terms hepatitis B + ( reactivation OR [drug or drug class linked to HBVr]). STUDY SELECTION AND DATA EXTRACTION: Relevant English-language cohort studies or randomized trials quantifying the incidence of HBVr secondary to pharmacotherapy among patients negative for hepatitis B surface antigen and DNA and positive for hepatitis B core antibody were included. DATA SYNTHESIS: Among 2045 articles, 102 met inclusion criteria. Receipt of rituximab was associated with the highest risk of HBVr (for oncological indication: 6.2% rate [225/3601 patients]) and subsequent hepatitis (up to 52.4% of all HBVr cases). Biologic agents for autoimmune disease were uncommonly associated with HBVr (2.4%, 56/2338), with only 4 cases of hepatitis, all attributable to rituximab. Reactivation caused by DAAs was rare (0.3%, 28/8398), with no cases of hepatitis. Relevance to Patient Care/Clinical Practice: This review compares and contrasts the incidence and clinical relevance of HBVr for various pharmacotherapies among patients with functionally cured hepatitis B, with discussion of appropriate risk mitigation strategies. CONCLUSIONS: Among patients with prior functional cure of hepatitis B, prophylactic antiviral therapy is recommended with rituximab administration irrespective of indication because of a high risk for HBVr-associated morbidity. Enhanced monitoring alone is reasonable for patients receiving nonrituximab biologics or DAAs.

Emergence of letermovir resistance in a lung transplant recipient with ganciclovir-resistant cytomegalovirus infection.

Following a year of valganciclovir prophylaxis, a lung transplant recipient developed cytomegalovirus (CMV) infection that became resistant to ganciclovir, as confirmed by detection of UL97 kinase mutation M460V and a previously uncharacterized UL54 DNA polymerase mutation L516P. The latter mutation is now shown to confer ganciclovir and cidofovir resistance. As predicted from the viral genotype, foscarnet therapy was effective, but resumption of valganciclovir as secondary prophylaxis resulted in a plasma viral load rebound to 3.6 log10 copies/mL several weeks later. Valganciclovir was then replaced by letermovir, resulting in gradual viral load reduction in the first 5 weeks to below the quantitation limit (2.7 log10 copies/mL) for 1 week, followed by 10 weeks of rising viral loads reaching 4.3 log10 copies/mL while on letermovir. At this point, CMV genotypic testing revealed UL56 mutation C325Y, which confers absolute resistance to letermovir. Retreatment with foscarnet was successful. This case adds to the considerable list of proven ganciclovir resistance mutations, and provides an early experience with letermovir resistance after off-label therapeutic use. This experience is consistent with in vitro observations of rapid emergence of letermovir-resistant CMV after drug exposure.

Patient preferences for treatment of acute bacterial skin and skin structure infections in the emergency department.

BACKGROUND: Limited research has assessed patient preferences for treatment disposition and antibiotic therapy of acute bacterial skin and skin structure infection (ABSSSI) in the emergency department (ED). Understanding patient preference for the treatment of ABSSSI may influence treatment selection and improve satisfaction. METHODS: A survey was conducted across 6 US hospital EDs. Patients with ABSSSI completed a baseline survey assessing preferences for antibiotic therapy (intravenous versus oral) and treatment location. A follow-up survey was conducted within 30-40 days after ED discharge to reassess preferences and determine satisfaction with care. RESULTS: A total of 94 patients completed both baseline and follow-up surveys. Sixty (63.8%) participants had a history of ABSSSI, and 69 (73.4%) were admitted to the hospital. Treatment at home was the most common preference reported on baseline and follow-up surveys. Patients with higher education were 82.2% less likely to prefer treatment in the hospital. Single dose intravenous therapy was the most commonly preferred antibiotic regimen on baseline and follow-up surveys (39.8 and 19.1%, respectively). Median satisfaction scores for care in the ED, hospital, home, and with overall antibiotic therapy were all 8 out of a maximum of 10. CONCLUSIONS: In these patients, the most common preference was for outpatient care and single dose intravenous antibiotics. Patient characteristics including higher education, younger age, and current employment were associated with these preferences. Opportunities exist for improving ABSSSI care and satisfaction rates by engaging patients and offering multiple treatment choices.

In Vitro Comparison of Ceftolozane-Tazobactam to Traditional Beta-Lactams and Ceftolozane-Tazobactam as an Alternative to Combination Antimicrobial Therapy for Pseudomonas aeruginosa.

Guidelines for the treatment of sepsis, febrile neutropenia, and hospital-acquired pneumonia caused by Pseudomonas aeruginosa include empirical regimens incorporating two antibiotics from different classes with activity against P. aeruginosa for select at-risk patients to increase the likelihood that the organism will be susceptible to at least one agent. The activity against P. aeruginosa and the rates of cross-resistance of ceftolozane-tazobactam were compared to those of the ß-lactam comparators cefepime, ceftazidime, piperacillin-tazobactam, and meropenem alone and cumulatively with ciprofloxacin or tobramycin. Nonurine P. aeruginosa isolates were collected from adult inpatients at 44 geographically diverse U.S. hospitals. MICs were determined using reference broth microdilution methods. Of the 1,257 isolates collected, 29% were from patients in intensive care units and 39% were from respiratory sites. The overall rate of susceptibility to ceftolozane-tazobactam was high at 97%, whereas it was 72 to 76% for cefepime, ceftazidime, piperacillin-tazobactam, and meropenem. The rate of nonsusceptibility to all four comparator ß-lactams was 11%; of the isolates nonsusceptible to the four comparator ß-lactams, 80% remained susceptible to ceftolozane-tazobactam. Among the isolates nonsusceptible to the tested ß-lactam comparators, less than half were susceptible to ciprofloxacin. By comparison, approximately 80% of the ß-lactam-nonsusceptible isolates were susceptible to tobramycin, for overall cumulative susceptibility rates of 94 to 95%, nearly 10% higher than that of the ciprofloxacin-ß-lactam combinations and approaching that of ceftolozane-tazobactam as a single agent. The rates of susceptibility to ceftolozane-tazobactam were consistently high, with little observable cross-resistance. Ceftolozane-tazobactam monotherapy performed at or above the level of commonly utilized combination therapies on the basis of in vitro susceptibilities. Ceftolozane-tazobactam should be considered for use in patients at high risk for resistant P. aeruginosa infection and as an alternative to empirical combination therapy, especially for patients unable to tolerate aminoglycosides.

New Gram Positive Agents to Treat Acute Bacterial Skin and Skin Structure Infections.

The FDA guidance published in 2013 provided requirements for conducting ABSSSI trials. In 2014, dalbavancin, oritavancin, and tedizolid were introduced into the market after phase III noninferiority clinical trials against vancomycin (for the lipoglycopeptides) and linezolid (for tedizolid), demonstrating clinical efficacy for the treatment of ABSSSI. Great interest exists for these agents because of the postulated financial impact. Due to favorable pharmacokinetics which allow for less frequent medication administration and shorter treatment durations, these agents may prove to reduce hospital admissions and length of stay.

Tolerability of low-dose sulfamethoxazole/trimethoprim for Pneumocystis jirovecii pneumonia prophylaxis in kidney transplant recipients.

Background- Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection seen in immunosuppressed patients, including solid-organ transplant recipients. Sulfamethoxazole/trimethoprim (SMX/TMP) has long been considered first-line therapy for PCP prophylaxis. Optimal dosing regimens in solid-organ transplant recipients have not been fully defined. Objective-To examine the tolerability of a 1-year, 3-times weekly, prophylactic regimen of a single-strength SMX/TMP tablet. Study Design-Single-center, retrospective cohort study. Setting-A tertiary-care medical center, including inpatient hospitalizations and outpatient transplant clinic visits. Patients-Adult patients who received a kidney transplant between December 1, 2010, and November 30, 2012, at Hartford Hospital. Patients receiving a concurrent extrarenal transplant were excluded. Patients' charts were reviewed for up to 1 year after transplant. Results-A total of 88 patients were included in the analysis. Sixty-seven patients finished a full year of SMX/TMP after transplant, 10 patients discontinued SMX/TMP less than 1 year after transplant, and 11 patients started taking atovaquone instead of SMX/TMP after transplant. Documented reasons for discontinuation included hyperkalemia, leukopenia, diarrhea, and simplification of medication regimen. Patients without a documented reason for discontinuation did not have any obvious anomalies in laboratory values that would account for the discontinuation. Patients who received atovaquone for PCP prophylaxis had higher rates of recurrent urinary tract infections than did patients who received SMX/TMP for prophylaxis (33% vs 7%, P = .02). A longer postoperative stay (median [interquartile range, IQR] 13 [8.25-26] days vs 7 [6-9.5] days, P = .02), higher rates of delayed graft function (50% vs 10%, P = .004), as well as higher serum creatinine levels on postoperative day 7 (6.25 [2.4-10.1] mg/dL vs 1.8 [1.2-4.2] mg/dL, P= .01), postoperative month 1 (1.9 [0.8] mg/dL vs 1.4 [0.5] mg/dL, P = .002), and postoperative month 12 (1.6 [0.5] mg/dL vs 1.3 [0.3] mg/dL, P = .04) were associated with early SMX/TMP discontinuation. Conclusion-A low-dose prophylactic SMX/TMP regimen of 1 single-strength tablet 3 times weekly is well tolerated. Discontinuation rates were lower than other rates reported for higher-dose regimens.

Carbapenem-Resistant Enterobacteriaceae: A Case Series of Infections at Hartford Hospital.

Infections due to carbapenem-resistant Enterobacteriaceae (CRE) represent a growing problem nationally, are difficult to treat, and are associated with high mortality rates. Features of CRE infection within Connecticut, a nonendemic area, have not been described in the medical literature. We report a case series of five patients with CRE isolates who were treated at Hartford Hospital in Hartford, Connecticut from 2011-2013. CRE isolates included three Klebsiella pneumoniae, one Klebsiella oxytoca, and two E. coli. Three isolates were obtained from urine cultures, one from respiratory culture, and one from blood and wound cultures. Four patients survived the hospital course, including three patients who had a hospital stay of > 100 days. In this nonendemic hospital, CRE infections were identified mainly in patients with multiple comorbidities who underwent catheter placement and surgical procedures, had contact with the health care system in the preceding 90 days, and tended to have prolonged, complicated hospital courses.

Clinical comparison of ertapenem and cefepime for treatment of infections caused by AmpC beta-lactamase-producing Enterobacteriaceae.

There are no comparative data evaluating outcomes of ertapenem treatment for infections with AmpC-producing Enterobacteriaceae. This retrospective matched case-control study was conducted between 2009 and 2012. Sixteen cases treated with ertapenem were matched 1:2 with 32 control cases treated with cefepime based on age, culture source, and hospital service. There were more cefepime-resistant organisms in the ertapenem group (cefepime resistance present in 44% of patients treated with ertapenem compared with 0% of control patients, p < 0.001). Ertapenem was used empirically in 25% of patients compared with 88% who received cefepime empirically (p < 0.001). Consequently, 56% of patients on ertapenem received inappropriate initial therapy compared with 9% of patients on cefepime (p < 0.001). No differences in clinical success were identified (69% for ertapenem vs 88% for cefepime, p = 0.138). Although a trend favoring cefepime could be suspected, it should be noted that no statistically significant difference in clinical success was detected despite the presence of more resistant organisms and delays in initiation of appropriate therapy among patients receiving ertapenem.

Early Experiences with Intrathecal Administration of Amphotericin B Liposomal Formulation at a Neurosurgical Center.

BACKGROUND: Intrathecal administration of amphotericin B represents an important adjunctive therapy for management of severe fungal meningitis. Intrathecal preparations have traditionally used amphotericin B deoxycholate. Liposomal amphotericin B is an alternative formulation with good clinical outcomes as systemic therapy, but scant data exist investigating intrathecal use. OBJECTIVE: The aim of this exploratory study was to evaluate outcomes following intrathecal administration of liposomal amphotericin B for treatment of severe fungal meningitis. METHODS: A national shortage of amphotericin B deoxycholate necessitated revision of institutional protocols at a southwestern neurosurgical center in Spring 2023. A starting intrathecal daily dose of 0.125-0.5 mg liposomal amphotericin B was recommended (dependent on insertion device), with 0.125-0.25 mg slow titration every 48 h and up to a 2 mg maximum daily dose. RESULTS: Four cases of fungal meningitis treated with adjunctive intrathecal amphotericin B liposomal formulation were reviewed. This included three cases of coccidioidal meningitis and one case of presumed Fusarium solani meningitis following an outbreak. All patients had initial disease improvement following initiation of intrathecal amphotericin B and were able to tolerate long-term therapy. One coccidioidal meningitis patient expired of neurologic complications shortly after being moved from the intensive care unit (ICU) to a floor unit. All other patients were successfully discharged from the hospital. New headache was the only reported adverse effect, which was managed with dose reduction and did not require therapy discontinuation. CONCLUSIONS: Liposomal amphotericin B may be feasibly administered intrathecally for the adjunctive treatment of severe fungal meningitis.

Early antibiotic discontinuation in patients with clinically suspected ventilator-associated pneumonia and negative quantitative bronchoscopy cultures.

OBJECTIVES: Preliminary data suggest that antibiotic discontinuation in patients with negative quantitative bronchoscopy and symptom resolution will not increase mortality. Because our hospital algorithm for antibiotic discontinuation rules out ventilator-associated pneumonia in the setting of negative quantitative bronchoscopy cultures, we compared antibiotic utilization and mortality in empirically treated, culture-negative ventilator-associated pneumonia patients whose antibiotic discontinuation was early versus late. DESIGN: Retrospective, observational cohort study. SETTING: Eight hundred sixty-seven bed, tertiary care, teaching hospital in Hartford, CT. PATIENTS: Eighty-nine patients with clinically suspected ventilator-associated pneumonia and a negative (<10 colony forming units/mL) quantitative bronchoscopy culture between January 2009 and March 2012. Early discontinuation patients (n = 40) were defined as those who had all antibiotic therapy stopped within one day of final negative culture report, whereas late discontinuation patients (n = 49) had antibiotics stopped later than one day. MEASUREMENTS: Univariate analyses assessed mortality, antibiotic duration, and frequency of superinfections. Multivariate logistic regression was performed to assess the effect of early discontinuation on hospital mortality. RESULTS: Patients had a mean ± SD Acute Physiology and Chronic Health Evaluation II score of 26.0 ± 6.0. Mortality was not different between early discontinuation (25.0%) and late discontinuation (30.6%) patients (p = 0.642). Antibiotic duration (days) was also not different for patients who died vs. those who survived (Median [interquartile range]: 3 [1-7.5] vs. 3 [1.75-6.25], respectively, p = 0.87), and when controlling for baseline characteristics and symptom resolution, only Acute Physiology and Chronic Health Evaluation II score was associated with hospital mortality on multivariate analyses. There were fewer superinfections (22.5% vs. 42.9%, p = 0.008), respiratory superinfections (10.0% vs. 28.6%, p = 0.036), and multidrug resistant superinfections (7.5% vs. 35.7%, p = 0.003), in early discontinuation compared with late discontinuation patients. CONCLUSIONS: In this severely ill population with clinically suspected ventilator-associated pneumonia and negative quantitative bronchoalveolar lavage cultures, early discontinuation of antibiotics did not affect mortality and was associated with a lower frequency of MDR superinfections.

Adherence and outcomes of a surgical prophylaxis guideline promoting cephalosporin use among patients with penicillin allergy.

BACKGROUND: The study purpose was to assess adherence to a local surgical prophylaxis guideline in patients with reported penicillin allergies, which recommends cephalosporins as first-line prophylaxis. METHODS: Adult patients with penicillin allergies admitted for a surgical procedure from July 2020 to June 2021 were retrospectively screened, and the first surgery per admission was included. The primary outcome was the proportion of surgeries using ß-lactam prophylaxis. Additional outcomes included prophylaxis timing, hypersensitivity reactions, acute kidney injury, infectious complications, duration of stay, and 30-day mortality or readmission. RESULTS: Among 597 procedures, 504 patients (84.4%) received a ß-lactam for surgical prophylaxis, including 494 (82.3%) who received a cephalosporin. Patients in the non-ß-lactam group were more likely to have a type I IgE-mediated penicillin allergy (48.4% vs 31.7%, P = .002); however, the majority with type I reactions still received ß-lactams (78.0%), including in the setting of anaphylaxis or angioedema to penicillin (67.7%). Zero allergic reactions to prophylaxis antibiotics were reported in either group, and there were no significant differences in the proportion of patients receiving drugs associated with the management of allergic reactions. Receipt of non-ß-lactams was associated with inappropriate prophylaxis timing (9.7% vs 3.2%, P = .005) and postprocedural acute kidney injury (7.5% vs 0.6%, P < .001). All other outcomes were nonsignificant between the groups. CONCLUSION: Among surgical patients with a documented penicillin allergy, most received cephalosporin prophylaxis as recommended by institutional guidelines, with zero allergic reactions. Receipt of non-ß-lactam prophylaxis was associated with worsened outcomes. Cephalosporin prophylaxis should be preferred for surgical patients, including in the setting of true penicillin allergy.