Citations

Abstract Background These recommendations provide guidance on the optimal timing for transitioning from intravenous to oral antibiotics in patients with complicated urinary tract infection (cUTI), especially in presence of associated Gram-negative bacteremia. Methods The panel's recommendations are based upon evidence derived from systematic literature reviews which focused on comparative benefits and harms of transitioning to oral therapy versus continuing parenteral therapy of the total duration of treatment, including publications since 2000. These recommendations 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. Results The guidelines panel suggests transitioning to oral antibiotics in patients with cUTI who are clinically improving, able to take medication, and for whom an effective oral option is available, rather than continuing parenteral therapy for the remaining treatment duration, regardless of the presence of associated Gram-negative bacteremia. An effective oral option needs to be active against the causative pathogen and achieve therapeutic levels in the urine and relevant tissue. Conclusions Parenteral and oral antibiotics used to complete treatment courses for cUTI provide similar efficacy and adverse events, especially in the context of shorter duration of therapy. This recommendation places a high value on reducing avoidable intravenous catheter-related adverse events, costs, and resources, as well as taking into account practical aspects of antibiotic administration.

Abstract Background These recommendations provide guidance on the optimal duration of antibiotics in patients with complicated urinary tract infection (cUTI), especially in presence of associated Gram-negative bacteremia. Methods The panel's recommendations are based upon evidence derived from systematic literature reviews which focused on comparative benefits and harms of shorter (5–7 days) vs prolonged (10–14 days) duration of antibiotics, including publications since 2000. These recommendations 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. Results The guidelines panel suggests that patients with cUTI who are improving on effective therapy can be treated with shorter duration of antimicrobials (either 5–7 days of a fluoroquinolone or 7 days of a non-fluoroquinolone) rather than longer courses of antibiotics, regardless of the presence of associated Gram-negative bacteremia. An effective antimicrobial agent achieves therapeutic levels in the urine and relevant tissue and is active against the causative pathogen. However, men with febrile UTI in whom acute bacterial prostatitis is suspected may benefit from a longer treatment duration (10–14 days), and a short courses of oral beta lactams may require higher doses for efficacy. Conclusions Shorter durations of antibiotics for cUTI provide similar efficacy as longer courses, except in men with febrile UTI in whom acute bacterial prostatitis is suspected. This recommendation places a high value on antibiotic stewardship considerations as well as reducing the burden of antimicrobial administration from a healthcare perspective and reducing the burden of taking antibiotics from a patient perspective.

Abstract Background These recommendations address the empiric choice of antibiotics in suspected complicated urinary tract infection (cUTI). Issues to balance include the need for appropriate initial empiric antimicrobial therapy, the patient's severity of illness, and antimicrobial stewardship concerns. Methods The panel's recommendations are based upon evidence derived from systematic literature reviews that focused on comparative benefits and harms of classes of antibiotics approved for cUTI, starting with publications from 2008 onwards, and our review of predictors of resistance in uropathogens included references identified since 2000. These recommendations 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. Results The guidelines panel suggests initially selecting among preferred empiric antibiotic choices rather than alternative options, stratified for the patient's severity of illness and antimicrobial stewardship considerations. When choosing among these antibiotics for a specific patient, the guideline panel suggests a 4-step process to account for changing resistance patterns and individualized patient needs. The steps are: (1) assess the severity of illness (for initial prioritization of antibiotics), (2) consider patient-specific risk factors for resistant uropathogens (for optimization of coverage), (3) evaluate other patient-specific considerations (to reduce the risk of adverse events), and (4) for patients with sepsis, consult a relevant local antibiogram if available (to further improve the likelihood of giving appropriate empiric therapy). Lastly, the guideline panel suggests selecting definitive effective therapy with a targeted spectrum based on the result of the urine culture. Conclusions Many of the classes of antibiotics approved to treat cUTI demonstrate similar efficacy as other classes of antibiotics in randomized controlled trials. Bacterial resistance prevalence is always changing, and new antibiotics will be developed. In this context, the guidelines panel provides recommendations for choosing empiric antibiotic therapy for cUTI that will help clinicians decide among available antibiotic options at the point of care.

Abstract Background Antimicrobial resistance (AMR) is undermining modern medicine, a problem compounded by bacterial adaptation to antibiotic pressures. Phages are viruses that infect bacteria. Their diversity and evolvability offer the prospect of their use as a therapeutic solution. Reported are outcomes of customized phage therapy for patients with difficult-to-treat antimicrobial resistant infections. Methods We retrospectively assessed 12 cases of customized phage therapy from a phage production center. Phages were screened, purified, sequenced, characterized, and Food and Drug Administration–approved via the IND (investigational new drug) compassionate-care route. Outcomes were assessed as favorable or unfavorable by microbiologic and clinical standards. Infections were device-related or systemic. Other experiences such as time to treatment, antibiotic synergy, and immune responses were recorded. Results Fifty requests for phage therapy were received. Customized phages were generated for 12 patients. After treatment, 42% (5/12) of cases showed bacterial eradication and 58% (7/12) showed clinical improvement, with two-thirds of all cases (66%) showing favorable responses. No major adverse reactions were observed. Antibiotic-phage synergy in vitro was observed in most cases. Immunological neutralization of phages was reported in 5 cases. Several cases were complicated by secondary infections. Complete characterization of the phages (morphology, genomics, and activity) and their production (methods, sterility, and endotoxin tests) are reported. Conclusions Customized phage production and therapy was safe and yielded favorable clinical or microbiological outcomes in two-thirds of cases. A center or pipeline dedicated to tailoring the phages against a patient's specific AMR bacterial infection may be a viable option where standard treatment has failed.

Abstract Urinary tract infections (UTIs) are among the most common bacterial infections in the United States and are a major driver of antibiotic use, both appropriate and inappropriate, across healthcare settings. Novel UTI diagnostics are a strategy that might enable better UTI treatment. Members of the Antibacterial Resistance Leadership Group Laboratory Center and the Infectious Diseases Society of America Diagnostics Committee convened to envision ideal future UTI diagnostics, with a view towards improving delivery of healthcare, patient outcomes and experiences, and antibiotic use, addressing which types of UTI diagnostics are needed and how companies might approach development of novel UTI diagnostics.