Brincidofovir for disease progression due to suspected tecovirimat resistance in association with advanced HIV.

A man with advanced HIV presented with verrucous plaques 2-3 months after initial mpox infection. He received two courses of tecovirimat without resolution of initial mpox lesions and development of new lesions raising concern for resistance. He was treated with two doses of brincidofovir and demonstrated improvement 6 months later.

Association of piperacillin and vancomycin exposure on acute kidney injury during combination therapy.

Objectives: Acute kidney injury (AKI) is a well-documented adverse effect observed with piperacillin/tazobactam in combination with vancomycin. The pharmacokinetics of these antibiotics when given in combination have not been previously evaluated. The purpose of this study was to compare the exposure of vancomycin + piperacillin/tazobactam in patients with and without AKI. Methods: Ninety adult patients, who received at least 72 h of vancomycin + piperacillin/tazobactam combination therapy and had available serum concentrations of vancomycin and piperacillin were included in the study. Nephrotoxicity was defined as a 1.5-fold increase in serum creatinine within 7 days from baseline. Median daily AUCs were calculated in those with nephrotoxicity (vancomycin + piperacillin/tazobactam 'N') versus those without nephrotoxicity (vancomycin + piperacillin/tazobactam 'WN') during the first 7 days of combination therapy. Results: The overall incidence of AKI in those receiving vancomycin + piperacillin/tazobactam was 20% (18/90). The median daily vancomycin AUCs did not differ between the vancomycin + piperacillin/tazobactam 'WN' and vancomycin + piperacillin/tazobactam 'N' groups. Although not statistically significant, the median daily vancomycin AUCs in the vancomycin + piperacillin/tazobactam 'N' group were numerically greater on Day 5 and trended downwards thereafter. For the piperacillin group, the median daily AUCs did not vary between groups, except on Day 7 where the vancomycin + piperacillin/tazobactam 'WN' group had statistically greater median piperacillin AUC than the vancomycin + piperacillin/tazobactam 'N' group (P = 0.046). Conclusions: Utilizing serum creatinine-defined AKI, our study did not find any significant differences in vancomycin and piperacillin/tazobactam exposure between the groups with and without nephrotoxicity. These data indicate that vancomycin + piperacillin/tazobactam should not be avoided due to the risk of overexposure; instead, clinicians should continue to use these therapies cautiously.

A 40-Year-Old Female With Mycobacterium abscessus Successfully Treated With a Dual Beta-Lactam Combination.

Nontuberculous mycobacteria (NTM) infections are difficult to treat conditions, specially Mycobacterium abscessus (Mab) lung disease. The most recent ATS/ERS/ESCMID/IDSA clinical practice guidelines (2020) recommend regimens of multiple intravenous (IV) and oral antibiotics. Recent in vitro studies on M. abscessus show that the combination of two beta-lactam antibiotics, as well as select beta-lactamase inhibitors, provides significant synergy in its treatment. We present the first in vivo case of the successful treatment of Mycobacterium abscessus with imipenem and amoxicillin in addition to macrolides, clofazimine, and inhaled liposomal amikacin.

Re-evaluation of cefepime or piperacillin/tazobactam to decrease use of carbapenems in ESBL-producing Enterobacterales urinary tract infections (REDUCE-UTI).

Objectives: To re-examine the use of non-carbapenems (NCBPs), specifically piperacillin/tazobactam and cefepime, for ESBL-producing Enterobacterales (ESBL-E) urinary tract infections (UTIs). Patients: Retrospective cohort study of adults hospitalized between January 2016 and June 2020 with pyuria on urinalysis, a urine culture positive for ESBL-E treated with a study antibiotic (meropenem, ertapenem, cefepime or piperacillin/tazobactam) and did not meet criteria for study exclusion. Methods: To compare carbapenems (CBPs) with cefepime or piperacillin/tazobactam for the treatment of ESBL-E UTI. The primary outcome was clinical cure, defined as complete resolution of signs and symptoms of infection. Secondary outcomes included in-hospital mortality, recurrence within 30 days and resistance emergence within 30 days. Results: One-hundred and thirty-three patients were included, based on definitive therapy received; 69 (51.9%) received CBP and 64 (48.1%) received NCBP therapy. Of the total patient population, 17 (12.8%) were admitted to the ICU, 84 (63.1%) had a complicated UTI and 64 (48.1%) had pyelonephritis. There was no difference in clinical cure between the CBP and NCBP groups (95.7% versus 96.9%, P = 0.999). Additionally, no differences in secondary outcomes were observed. Conclusions: When compared with CBPs, cefepime and piperacillin/tazobactam resulted in similar clinical cure, in-hospital mortality, recurrence and resistance emergence in the treatment of ESBL-E UTI.

Implementation of a ß-lactam therapeutic drug monitoring program: Experience from a large academic medical center.

PURPOSE: To describe the implementation and operationalization of a ß-lactam (BL) therapeutic drug monitoring (TDM) program at a large academic center. SUMMARY: BLs are the most used class of antibiotics. Suboptimal antibiotic exposure is a significant concern in hospitalized patients, particularly in those with altered pharmacokinetics. BL-TDM provides clinicians the opportunity to optimize drug concentrations to ensure maximal therapeutic efficacy while minimizing toxicity. However, BL-TDM has not been widely adopted due to the lack of access to assays. The University of Florida Shands Hospital developed a BL-TDM program in 2015. This is a consultative service primarily run by pharmacists and is conducted in all patient care areas. An analysis was performed on the first BL-TDM encounter for 1,438 patients. BL-TDM was most frequently performed for cefepime (61%, n = 882), piperacillin (15%, n = 218), and meropenem (11%, n = 151). BL-TDM was performed a median of 3 days (interquartile range, 1-5 days) from BL initiation. Among patients with available minimum inhibitory concentration (MIC) values and trough concentrations, the pharmacokinetic/pharmacodynamic (PK/PD) target of 100% fT>MIC was attained in 308 patients (88%). BL-TDM resulted in a dosage adjustment in 25% (n = 361) of patients. CONCLUSION: Implementation of a BL-TDM program requires the concerted efforts of physicians, pharmacists, nursing staff, phlebotomists, and personnel in the analytical laboratory. Standard antibiotic dosing failed to achieve optimal PK/PD targets in all patients; utilizing BL-TDM, dose adjustments were made in 1 of every 4 patients.

Resource Over-Utilization in Hospitalized Patients With Uncomplicated Skin and Soft Tissue Infections.

BACKGROUND: Inpatient management of SSTIs utilizes considerable healthcare resources. The CREST+SEWS score categorizes patients with SSTIs into 4 severity classes. Hospitalizations can be avoided in Class I as they are treated as outpatients with oral antibiotics, whereas Class IV require hospitalization for intravenous antibiotics. OBJECTIVE: The purpose of this study was to perform a budget impact analysis on CREST+SEWS Class 1 patients, to compare the medical costs of current treatment, in the inpatient setting with intravenous antibiotics, with a proposed alternative of using oral antibiotics in the outpatient setting. Further, resource utilization in Class I was evaluated. METHODS: This was a retrospective study of adult patients hospitalized in 2015 for SSTIs who received >24 hours of antimicrobials. The CREST+SEWS scoring system was used to stratify patients into Class I to IV. Pharmacy and medical costs and resources associated with inpatient management of Class I SSTIs were derived from the itemized discharge records. RESULTS: Of the 252 patients who met the inclusion criteria, 61 (24%) were classified as Class I. The total cost of treating Class I SSTI patients in the inpatient setting was $281,816 (cost per patient: $4,619) in 2015 USD. In the hypothetical situation of treatment with oral antibiotics in the outpatient setting, the cost savings were estimated to be $4,398 per patient. Fifty-three percent of patients had blood cultures, and on average, each patient received 2 radiographic tests. CONCLUSIONS: Identifying outpatient candidates, and avoiding tests with low diagnostic can reduce the economic burden of SSTIs.

Re-evaluation of cefepime or piperacillin-tazobactam to decrease use of carbapenems in extended-spectrum beta-lactamase-producing Enterobacterales bloodstream infections (REDUCE-BSI).

Objective: To re-examine the use of noncarbapenems (NCBPs), specifically piperacillin-tazobactam (PTZ) and cefepime (FEP), for extended-spectrum beta-lactamase-producing Enterobacterales bloodstream infections (ESBL-E BSIs). Design: Retrospective cohort study. Setting: Tertiary-care, academic medical center. Patients: The study included patients hospitalized between May 2016 and May 2019 with a positive blood culture for ESBL-E. Patients were excluded if they received treatment with antibiotics other than meropenem, ertapenem, PTZ, or FEP. Patients were also excluded if they were aged <18 years, received antibiotics for <24 hours, were treated for polymicrobial BSI, or received concomitant antibiotic therapy for a separate gram-negative infection. Methods: We compared CBPs with FEP or PTZ for the treatment of ESBL-E BSI. The primary outcome was in-hospital mortality. Secondary outcomes included clinical cure, microbiologic cure, infection recurrence, and resistance development. Results: Data from 114 patients were collected and analyzed; 74 (65%) patients received carbapenem (CBP) therapy and 40 (35%) patients received a NCBP (30 received FEP and 10 received PTZ). The overall in-hospital mortality was 6% (N = 7), with a higher death rate in the CBP arm than in the N-CBP arm, (8% vs 3%; P = .42). No difference in mortality was detected between subgroups with Pitt bacteremia score ≥4, those requiring ICU admission, those whose infections were cause by a nongenitourinary source or causative organism (ie, 76 had Escherichia coli and 38 had Klebsiella spp). We detected no differences in secondary outcomes between the groups. Conclusion: Compared to CBPs, FEP and PTZ did not result in greater mortality or decreased clinical efficacy for the treatment of ESBL-E BSI caused by susceptible organisms.

Draft Genome Sequence of a Burkholderia cepacia Complex Strain Isolated from a Human Intra-abdominal Abscess.

Burkholderia cepacia complex (Bcc) bacteria are opportunistic pathogens with high transmissibility and mortality. Here, we report the draft genome sequence of a Bcc strain isolated from a deep abscess culture in an immunocompetent patient with no relevant prior medical history.

Decreased antibiotic exposure using a procalcitonin protocol for respiratory infections and sepsis in US community hospitals (ProCommunity).

OBJECTIVE: Antibiotic overuse leading to antimicrobial resistance is a global public health concern. Clinical trials have demonstrated that procalcitonin-based decision-making for antibiotic therapy can safely decrease inappropriate antibiotic use in patients with respiratory infections and sepsis, but real-world data are scarce. This study sought to assess the impact of a procalcitonin-based antibiotic stewardship program (protocol plus education) on antibiotic use in community hospitals. METHODS: An observational, retrospective, matched cohort study was conducted. Eligible patients treated in hospitals with a procalcitonin-based protocol plus education (Procalcitonin cohort hospitals) were matched to patients admitted to facilities without procalcitonin testing (Control cohort hospitals) using a 1:2 ratio. The Control hospitals were facilities where procalcitonin testing was not available on site. Patient matching was based on: (1) age, (2) gender, (3) admission diagnosis code using groupings of the International Classification of Diseases, 10th Revision, (4) whether patients were admitted to the intensive care unit, and (5) whether a blood culture test was performed. Procalcitonin cohort hospitals implemented a quality improvement initiative, where procalcitonin was available, used regularly, and clinicians (physicians and pharmacists) were educated on its use. RESULTS: After adjustment, patients in the Procalcitonin cohort had 1.47 fewer antibiotic days (9.1 vs. 8.5 days, 95%CI: -2.72; -0.22, p = .021). There was no difference in length of stay or adverse clinical outcomes except for increase in acute kidney injury (odds ratio = 1.26, 95%CI: 1.01; 1.58, p = .038). CONCLUSIONS: Patients with respiratory infections and sepsis in hospitals utilizing a procalcitonin-based protocol coupled with education received fewer days of antibiotic therapy.

Dissemination mechanisms of NDM genes in hospitalized patients.

BACKGROUND: NDM-producing Enterobacteriaceae are a major clinical concern worldwide. We characterized NDM-positive pathogens isolated from patients and assessed the dissemination patterns of the bla NDM genes in a hospital setting. METHODS: Eleven NDM-positive Enterobacteriaceae (three Enterobacter hormaechei, six Klebsiella pneumoniae and two Escherichia coli) were isolated from nine patients over a 1 year period. Antimicrobial susceptibility was assessed by MICs. A combination of short- and long-read WGS was used for genome analysis. Clinical treatment history of patients was linked with genetic features of individual isolates to investigate the dissemination patterns of the bla NDM genes and NDM-positive strains. RESULTS: bla NDM in clonal K. pneumoniae were transmitted between two patients. In other instances, an identical IncC plasmid encoding NDM-1 was transmitted between E. coli and K. pneumoniae isolated from the same patient, and an IncX3 plasmid, carrying bla NDM-1 or bla NDM-5, was harboured in non-clonal E. hormaechei. Varying patterns of IS elements were identified as a critical transmission mechanism in association with bla NDM genes. CONCLUSIONS: Multiple transmission patterns were identified in hospitalized patients, including dissemination of clonal bacterial strains carrying resistance genes and horizontal transfer of resistance genes among divergent bacterial strains. Controlling spread of NDM is complex: while attention to standard infection control practices is critically important, this needs to be matched by aggressive efforts to limit unnecessary antimicrobial use, to minimize the selection for and risk of transfer of 'high mobility' resistance genes among Enterobacteriaceae.

ProCommunity: procalcitonin use in real-world US community hospital settings.

OBJECTIVE: Procalcitonin (PCT) is a biomarker that may help providers optimize antibiotic (AB) therapy. Numerous clinical trials have demonstrated the utility of PCT-guided decision algorithms in treating lower respiratory tract infections and sepsis, but evidence from real-world studies is limited. This study sought to evaluate the effects of PCT on select clinical outcomes in community hospitals. METHODS: An observational, retrospective, case-control study was conducted. Hospitals from a large US hospital system were categorized into "treatment" and "control" hospitals. Treatment hospitals were those with in-house PCT testing, a pharmacy team tasked with PCT testing follow-up and results in the patient's electronic medical records alongside a recommendation on AB treatment. Control hospitals either did not have PCT testing available in house or sent out tests to a laboratory or neighboring facility. Patients from treatment hospitals were matched 1:1 to patients from control hospitals based on admission diagnosis code, sex, age and whether an intensive care unit admission was observed. Clinical outcomes included number of days of AB treatment, length of stay, 30 day readmissions, mortality and acute kidney injury. Comparisons were conducted using multivariable regressions accounting for clustering at the hospital level. RESULTS: Patients from treatment hospitals had significantly shorter hospital stays (-0.68 days, 95% CI: -1.26, -0.09; p = .02). A reduction in days of AB treatment (-1.50 days, 95% CI: -3.27, 0.27; p = .10) was observed, but did not reach statistical significance. CONCLUSION: These findings suggest that PCT, along with specific treatment recommendations, may lead to shortened hospital stays with no adverse outcome on patient safety.

A HAART-Breaking Review of Alternative Antiretroviral Administration: Practical Considerations with Crushing and Enteral Tube Scenarios.

Selection of an appropriate antiretroviral regimen for the patient infected with human immunodeficiency virus can be challenging, as various considerations must be taken into account including viral resistance mutations, patient comorbidities, drug interactions, and the potential for drug-related adverse effects and toxicities. Treatment is further complicated when a clinical scenario arises requiring an alteration in the dosage form. Factors ranging from dysphagia to administration through an enteral feeding tube can affect decisions regarding antiretroviral dosage forms. Limited pharmacokinetic data exist regarding the alteration of antiretroviral medications from their original form. Bioavailability may vary substantially between dosage forms, which can lead to unpredictable drug concentrations. Supratherapeutic or subtherapeutic antiretroviral drug concentrations can result in increased toxicity, virologic failure, or the emergence of drug resistance. We performed a systematic literature search to review the available antiretroviral literature on the modification of solid dosage forms as well as alternative routes of administration of oral antiretroviral agents and their application to clinical practice.