2024 Clinical Practice Guideline by the Infectious Diseases Society of America on Complicated Intra-abdominal Infections: Utility of Intra-abdominal Fluid Cultures in Adults, Children, and Pregnant People.

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for obtaining cultures of intra-abdominal fluid in patients with known or suspected intra-abdominal infection. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.

2024 Clinical Practice Guideline Update by the Infectious Diseases Society of America on Complicated Intra-abdominal Infections: Diagnostic Imaging of Suspected Acute Intra-abdominal Abscess in Adults, Children, and Pregnant People.

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for diagnostic imaging of suspected acute intra-abdominal abscess. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.

2024 Clinical Practice Guideline Update by the Infectious Diseases Society of America on Complicated Intra-abdominal Infections: Diagnostic Imaging of Suspected Acute Appendicitis in Adults, Children, and Pregnant People.

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for diagnostic imaging of suspected acute appendicitis. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.

2024 Clinical Practice Guideline Update by the Infectious Diseases Society of America on Complicated Intra-abdominal Infections: Diagnostic Imaging of Suspected Acute Cholecystitis and Acute Cholangitis in Adults, Children, and Pregnant People.

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for diagnostic imaging of suspected acute cholecystitis or acute cholangitis. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.

2024 Clinical Practice Guideline Update by the Infectious Diseases Society of America on Complicated Intra-abdominal Infections: Utility of Blood Cultures in Adults, Children, and Pregnant People.

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for obtaining blood cultures in patients with known or suspected intra-abdominal infection. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.

2024 Clinical Practice Guideline Update by the Infectious Diseases Society of America on Complicated Intra-abdominal Infections: Risk Assessment, Diagnostic Imaging, and Microbiological Evaluation in Adults, Children, and Pregnant People.

As the first part of an update to the clinical practice guideline on the diagnosis and management of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America, the panel presents twenty-one updated recommendations. These recommendations span risk assessment, diagnostic imaging, and microbiological evaluation. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach.

2024 Clinical Practice Guideline Update by the Infectious Diseases Society of America on Complicated Intra-abdominal Infections: Diagnostic Imaging of Suspected Acute Diverticulitis in Adults and Pregnant People.

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for diagnostic imaging of suspected acute diverticulitis. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.

2024 Clinical Practice Guideline Update by the Infectious Diseases Society of America on Complicated Intra-abdominal Infections: Risk Assessment in Adults and Children.

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides a recommendation for risk stratification according to severity of illness score. The panel's recommendation is based upon evidence derived from systematic literature reviews and adheres to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach.

Stewardship-Guided T2Candida Testing Shortens Time to Antifungal Treatment and Reduces Antifungal Usage Among Medical Intensive Care Unit Patients With Septic Shock.

Background: Diagnosis of invasive candidiasis (IC) is limited by insensitivity and slow turnaround of cultures. Our objectives were to define the performance of T2Candida, a nonculture test, under guidance of a diagnostic stewardship program, and evaluate impact on time to antifungal initiation and antifungal utilization. Methods: This was a retrospective study of adult medical intensive care unit (MICU) patients with septic shock for whom T2Candida testing was performed from March 2017 to March 2020. Patients with positive T2Candida results during this period were compared to MICU patients who did not undergo T2Candida testing but had septic shock and blood cultures positive for Candida from January 2016 through March 2020. Results: Overall, 155 T2Candida tests from 143 patients were included. Nine percent of T2Candida tests were positive compared to 4.5% of blood cultures. Sensitivity, specificity, positive predictive value, and negative predictive value of T2Candida for proven and probable IC were 78%, 95%, 50%, and 99%, respectively. Patients who tested positive for T2Candida (n = 14) were diagnosed earlier and initiated on antifungal therapy sooner than patients with IC (n = 14) diagnosed by blood culture alone (median, 5.6 vs 60 hours; P < .0001). Median antifungal days of therapy/1000 patient-days were 23.3/month preimplementation and 15/month postimplementation (P  = .007). Following a negative T2Candida result, empiric antifungals were either not administered in 58% or discontinued within 72 hours in 96% of patients. Conclusions: Diagnostic stewardship guided T2Candida testing resulted in reduced time to IC diagnosis, faster initiation of antifungal therapy, and lower antifungal usage among MICU patients with septic shock.

Impact of Rapid Identification and Stewardship Intervention on Coagulase-Negative Staphylococcus Bloodstream Infection.

We investigated the impact of rapid diagnostic testing with and without algorithm-based stewardship recommendations on antibiotic use for bloodstream infection with coagulase-negative staphylococci. A significant reduction in antibiotic days of therapy was achieved in the stewardship intervention group that was not seen with rapid diagnostic testing alone.

Open-source institutional guideline recommendations during the COVID-19 pandemic.

PURPOSE: The global coronavirus disease 2019 (COVID-19) pandemic and the search for ways in which to provide the best available care have created unprecedented times in terms of rapidly evolving reports of available treatment options. The primary objective of our analysis was to categorize online, open-source guidance to determine how US institutions approached their recommendations for management of patients with COVID-19 in the early weeks of the pandemic. METHODS: A search for open-source, online institutional guidelines for the treatment of COVID-19 was conducted using predefined criteria. The search was limited to the United States and conducted from April 12 through 14, 2020, and again on April 22, 2020. Searches were conducted at 2 points in time in order to identify changes in treatment recommendations due to evolving literature or institutional experience. Treatment recommendations, including guidance on antiviral therapy, corticosteroid and interleukin-6 inhibitor use, and nutritional supplementation were compared. RESULTS: Of the 105 institutions that met initial screening criteria, 14 institutions (13.3%) had online COVID-19 guidance available. Supportive care and clinical trial enrollment were the primary recommendations in all evaluated guidance. Recommendations to consider antimicrobial and adjunctive therapy varied. Eighty-six percent of guidelines contained recommendations for use, or consideration of use, of hydroxychloroquine. Guidance from 2 institutions mentioned use of hydroxychloroquine and azithromycin in combination. Of the 13 institutions listing hydroxychloroquine dosing recommendations, 62% recommended maintenance dosing of 200 mg twice daily. Infectious diseases or other specialty consultation was required by 89% of institutions using interleukin-6 inhibitors for COVID-19 management. CONCLUSION: Overall, the analysis revealed variability in treatment or supplemental pharmacologic therapy for the management of COVID-19.

Estimating the Treatment of Carbapenem-Resistant Enterobacteriaceae Infections in the United States Using Antibiotic Prescription Data.

BACKGROUND: Polymyxins (colistin, polymyxin B) have been first-line antibiotics against carbapenem-resistant Enterobacteriaceae (CRE) infections. New anti-CRE antibiotics (ceftazidime-avibactam, meropenem-vaborbactam, plazomicin) improve outcomes in CRE-infected patients and reduce toxicity compared with polymyxins. It is unclear how widely polymyxins and newer agents are used to treat CRE infections. METHODS: We conducted an online survey of US hospital-based pharmacists to determine antibiotic positioning against CRE infections. Numbers of all infections and CRE infections treated with different antibiotics in the United States were determined using IQVIA prescription data and Driving Re-investment in Research and Development and Responsible Antibiotic Use (DRIVE-AB) estimates of CRE infections. RESULTS: Ceftazidime-avibactam, meropenem-vaborbactam, or plazomicin were positioned as first-line agents against CRE pneumonia, bacteremia, intra-abdominal infections, and urinary tract infections at 87%, 90%, 83%, and 56% of surveyed US hospitals, respectively. From February 2018 to January 2019, an estimated 9437 and 7941 CRE infections were treated with an intravenous polymyxin or new agent, respectively; these figures represented ~28% (range, 19%-50%) and ~23% (range, 16%-42%) of CRE infections in the United States. Use of ceftazidime-avibactam, meropenem-vaborbactam, or plazomicin exceeded that of intravenous polymyxins against CRE infections as of December 2018. Currently, the new drugs are estimated to treat 35% (23% to 62%) of CRE infections in which they were expected to be first-line agents. CONCLUSIONS: New anti-CRE agents recently surpassed intravenous polymyxins as treatment for CRE infections, but use is less than expected from their positioning at US hospitals. Research on behavioral and economic factors that impact use of new antibiotics is needed, as are financial "pull" incentives that promote an economically viable marketplace.

Antimicrobial treatment challenges in the era of carbapenem resistance.

Infections due to carbapenem-resistant Gram-negative bacteria are burdened by high mortality and represent an urgent threat to address. Clinicians are currently at a dawn of a new era in which antibiotic resistance in Gram-negative bacilli is being dealt with by the availability of the first new antibiotics in this field for many years. Although new antibiotics have shown promising results in clinical trials, there is still uncertainty over whether their use will improve clinical outcomes in real world practice. Some observational studies have reported a survival benefit in carbapenem-resistant Enterobacteriaceae bloodstream infections using combination therapy, often including "old" antibiotics such as colistin, aminoglycosides, tigecycline, and carbapenems. These regimens, however, are linked to increased risk of antimicrobial resistance, and their efficacy has yet to be compared to new antimicrobial options. While awaiting more definitive evidence, antibiotic stewards need clear direction on how to optimize the use of old and novel antibiotic options. Furthermore, carbapenem-sparing regimens should be carefully considered as a potential tool to reduce selective antimicrobial pressure.

Ceftolozane-Tazobactam for the Treatment of Multidrug-Resistant Pseudomonas aeruginosa Infections: Clinical Effectiveness and Evolution of Resistance.

Background: Data on the use of ceftolozane-tazobactam and emergence of ceftolozane-tazobactam resistance during multidrug resistant (MDR)-Pseudomonas aeruginosa infections are limited. Methods: We performed a retrospective study of 21 patients treated with ceftolozane-tazobactam for MDR-P. aeruginosa infections. Whole genome sequencing and quantitative real-time polymerase chain reaction were performed on longitudinal isolates. Results: Median age was 58 years; 9 patients (43%) were transplant recipients. Median simplified acute physiology score-II (SAPS-II) was 26. Eighteen (86%) patients were treated for respiratory tract infections; others were treated for bloodstream, complicated intraabdominal infections, or complicated urinary tract infections. Ceftolozane-tazobactam was discontinued in 1 patient (rash). Thirty-day all-cause and attributable mortality rates were 10% (2/21) and 5% (1/21), respectively; corresponding 90-day mortality rates were 48% (10/21) and 19% (4/21). The ceftolozane-tazobactam failure rate was 29% (6/21). SAPS-II score was the sole predictor of failure. Ceftolozane-tazobactam resistance emerged in 3 (14%) patients. Resistance was associated with de novo mutations, rather than acquisition of resistant nosocomial isolates. ampC overexpression and mutations were identified as potential resistance determinants. Conclusions: In this small study, ceftolozane-tazobactam was successful in treating 71% of patients with MDR-P. aeruginosa infections, most of whom had pneumonia. The emergence of ceftolozane-tazobactam resistance in 3 patients is worrisome and may be mediated in part by AmpC-related mechanisms. More research on treatment responses and resistance during various types of MDR-P. aeruginosa infections is needed to define ceftolozane-tazobactam's place in the armamentarium.

Ceftazidime-Avibactam Is Superior to Other Treatment Regimens against Carbapenem-Resistant Klebsiella pneumoniae Bacteremia.

There are no data comparing outcomes of patients treated with ceftazidime-avibactam versus comparators for carbapenem-resistant Enterobacteriaceae infections. At our center, ceftazidime-avibactam treatment of carbapenem-resistant Klebsiella pneumoniae bacteremia was associated with higher rates of clinical success (P = 0.006) and survival (P = 0.01) than other regimens. Across treatment groups, there were no differences in underlying diseases, severity of illness, source of bacteremia, or strain characteristics (97% produced K. pneumoniae carbapenemase). Aminoglycoside- and colistin-containing regimens were associated with increased rates of nephrotoxicity (P = 0.002).

Carbapenem-Resistant Pseudomonas aeruginosa Bacteremia: Risk Factors for Mortality and Microbiologic Treatment Failure.

We reviewed 37 patients treated for bacteremia due to carbapenem-resistant (CR) Pseudomonas aeruginosa Although 65% of isolates were multiple-drug resistant, therapeutic options were available, as all were susceptible to ≥1 antibiotic. A total of 92% of patients received active antimicrobial therapy, but only 57% received early active therapy (within 48 h). Fourteen-day mortality was 19%. Microbiologic failure occurred in 29%. The Pitt bacteremia score (P = 0.046) and delayed active therapy (P = 0.027) were predictive of death and microbiologic failure, respectively.

Dosing Practices of Intravenous Acyclovir for Herpes Encephalitis in Obesity: Results of a Pharmacist Survey.

BACKGROUND: Dosing of intravenous acyclovir for herpes encephalitis in obese patients is recommended to be based on ideal body weight. However, limited data support this recommendation, and recent data suggest this may lead to underdosing. OBJECTIVE: To determine national dosing practices of intravenous acyclovir across a range of patient weights. METHODS: A survey was distributed to members of the American College of Clinical Pharmacy Critical Care and Infectious Diseases Practice & Research Networks listservs. Data collected included demographic information and dosing of acyclovir, given consistent patient cases with varying patient weight. RESULTS: A total of 264 pharmacists participated in the survey, with 240 (90.9%) participants completing the survey. Participants were predominately clinical pharmacists. As patient weight increased, respondents were more apt to dose based on an adjusted body weight, with dosing in the obese and morbidly obese showing a clear lack of consistency. CONCLUSIONS: Intravenous dosing of acyclovir for herpes encephalitis is variable, especially in obese patients, and does not reflect recommendations. Limited data provide conflicting recommendations for dosing in obese patients, and future studies are necessary to optimize patient outcomes and prevent toxicity.

Clinical Outcomes, Drug Toxicity, and Emergence of Ceftazidime-Avibactam Resistance Among Patients Treated for Carbapenem-Resistant Enterobacteriaceae Infections.

Thirty-seven carbapenem-resistant Enterobacteriaceae (CRE)-infected patients were treated with ceftazidime-avibactam. Clinical success and survival rates at 30 days were 59% (22/37) and 76% (28/37), respectively. In 23% (5/22) of clinical successes, CRE infections recurred within 90 days. Microbiologic failure rate was 27% (10/37). Ceftazidime-avibactam resistance was detected in 30% (3/10) of microbiologic failures.

Evaluation of the In Vitro Activity of Ceftazidime-Avibactam and Ceftolozane-Tazobactam against Meropenem-Resistant Pseudomonas aeruginosa Isolates.

We compared ceftazidime-avibactam, ceftolozane-tazobactam, ceftazidime, cefepime, and piperacillin-tazobactam MICs for 38 meropenem-resistant Pseudomonas aeruginosa isolates. No isolates harbored carbapenemases; 74% were oprD mutants. Ceftazidime-avibactam and ceftolozane-tazobactam were active against 92% of the isolates, including 80% that were resistant to all three ß-lactams. Forty-three percent of ceftazidime-avibactam-susceptible isolates and 6% of ceftolozane-tazobactam-susceptible isolates exhibited MICs at the respective breakpoints. Ceftolozane-tazobactam and ceftazidime-avibactam are therapeutic options for meropenem-resistant P. aeruginosa infections that should be used judiciously to preserve activity.