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Intra-abdominal infections (IAIs) are an important cause of morbidity and mortality in hospital settings worldwide. The cornerstones of IAI management include rapid, accurate diagnostics; timely, adequate source control; appropriate, short-duration antimicrobial therapy administered according to the principles of pharmacokinetics/pharmacodynamics and antimicrobial stewardship; and hemodynamic and organ functional support with intravenous fluid and adjunctive vasopressor agents for critical illness (sepsis/organ dysfunction or septic shock after correction of hypovolemia). In patients with IAIs, a personalized approach is crucial to optimize outcomes and should be based on multiple aspects that require careful clinical assessment. The anatomic extent of infection, the presumed pathogens involved and risk factors for antimicrobial resistance, the origin and extent of the infection, the patient's clinical condition, and the host's immune status should be assessed continuously to optimize the management of patients with complicated IAIs.
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Infecciones Intraabdominales , Humanos , Infecciones Intraabdominales/tratamiento farmacológico , Factores de Riesgo , Antibacterianos/uso terapéuticoRESUMEN
Antimicrobial resistance in gram-negative pathogens, such as Acinetobacter baumannii, is a serious threat to human health. Sulbactam-durlobactam, a unique ß-lactam and a ß-lactamase inhibitor combination, is a novel agent targeted against carbapenem-resistant A. baumannii. This supplement provides a summary of the development of SUL-DUR, discussing its unique features and role in treating infections caused by CRAB pathogens.
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Infecciones por Acinetobacter , Acinetobacter baumannii , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Infecciones por Acinetobacter/tratamiento farmacológico , Sulbactam/farmacología , Sulbactam/uso terapéutico , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Pruebas de Sensibilidad MicrobianaRESUMEN
There is a crucial need for novel antibiotics to stem the tide of antimicrobial resistance, particularly against difficult to treat gram-negative pathogens like Acinetobacter baumannii-calcoaceticus complex (ABC). An innovative approach to addressing antimicrobial resistance may be pathogen-targeted development programs. Sulbactam-durlobactam (SUL-DUR) is a ß-lactam/ß-lactamase inhibitor combination antibiotic that is being developed to specifically target drug-resistant ABC. The development of SUL-DUR culminated with the Acinetobacter Treatment Trial Against Colistin (ATTACK) trial, a global, randomized, active-controlled phase 3 clinical trial that compared SUL-DUR with colistin for treating serious infections due to carbapenem-resistant ABC. SUL-DUR met the primary noninferiority endpoint of 28-day all-cause mortality. Furthermore, SUL-DUR had a favorable safety profile with a statistically significant lower incidence of nephrotoxicity compared with colistin. If approved, SUL-DUR could be an important treatment option for infections caused by ABC, including carbapenem-resistant and multidrug-resistant strains. The development program and the ATTACK trial highlight the potential for pathogen-targeted development programs to address the challenge of antimicrobial resistance.
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Infecciones por Acinetobacter , Acinetobacter baumannii , Humanos , Colistina/efectos adversos , Infecciones por Acinetobacter/tratamiento farmacológico , Antibacterianos/efectos adversos , Sulbactam/farmacología , Sulbactam/uso terapéutico , Carbapenémicos/farmacología , Inhibidores de beta-Lactamasas/uso terapéutico , Pruebas de Sensibilidad Microbiana , Farmacorresistencia Bacteriana MúltipleRESUMEN
The ongoing spread of antimicrobial resistance has made the treatment of uncomplicated urinary tract infections (UTIs) and urogenital gonorrhoea increasingly difficult. New oral treatment options are urgently needed. Gepotidacin (previously GSK2140944) is a novel, bactericidal, oral, 'first-in-class' triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by blocking two essential topoisomerase enzymes. Mutations in both enzymes would likely be necessary for resistance to occur, thus raising hopes that the drug will be able to maintain long-term effectiveness. Data from Phase II clinical trials of gepotidacin in UTIs and urogenital gonorrhoea appear promising, and Phase III trials are underway. In this review we summarize the development of gepotidacin and discuss its potential role in clinical practice. If approved, gepotidacin will be the first new oral antibiotic for UTIs in more than 20 years.
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Gonorrea , Infecciones Urinarias , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Gonorrea/tratamiento farmacológico , Gonorrea/microbiología , Acenaftenos/uso terapéutico , Acenaftenos/farmacología , Infecciones Urinarias/tratamiento farmacológicoRESUMEN
Candida auris is an emerging, multidrug resistant fungal pathogen that causes considerable morbidity and mortality. First identified in Japan in 2009, it has since been reported in more than 40 countries. C. auris can persist for long periods on different environmental surfaces as well as the skin. Clinical isolates are typically resistant to commonly prescribed antifungal drugs. Increasingly recognized as a cause of infections and outbreaks in nosocomial settings, C. auris is difficult to identify using traditional microbiological methods. One of the main reasons for the ongoing spread of C. auris is the multitude of virulence factors it possesses and uses against its human host that enables fungal persistence on the skin surface. Yet, many of the virulence mechanismsare unknown or remain incompletely understood. In this review, we summarize the evolution of virulence of C. auris, offer recommendations for combating this important human pathogen, and suggest directions for further research.
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Antimicrobial resistance is a global threat. As "proof-of-concept," we employed a system-based approach to identify patient, bacterial, and drug variables contributing to mortality in patients with carbapenem-resistant Klebsiella pneumoniae (CRKp) bloodstream infections exposed to colistin (COL) and ceftazidime-avibactam (CAZ/AVI) as mono- or combination therapies. Patients (n = 49) and CRKp isolates (n = 22) were part of the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE-1), a multicenter, observational, prospective study of patients with carbapenem-resistant Enterobacterales (CRE) conducted between 2011 and 2016. Pharmacodynamic activity of mono- and combination drug concentrations was evaluated over 24 h using in vitro static time-kill assays. Bacterial growth and killing dynamics were estimated with a mechanism-based model. Random Forest was used to rank variables important for predicting 30-day mortality. Isolates exposed to COL+CAZ/AVI had enhanced early bacterial killing compared to CAZ/AVI alone and fewer incidences of regrowth compared to COL and CAZ/AVI. The mean coefficient of determination (R2) for the observed versus predicted bacterial counts was 0.86 (range: 0.75 - 0.95). Bacterial subpopulation susceptibilities and drug mechanistic synergy were essential to describe bacterial killing and growth dynamics. The combination of clinical (hypotension), bacterial (IncR plasmid, aadA2, and sul3) and drug (KC50) variables were most predictive of 30-day mortality. This proof-of-concept study combined clinical, bacterial, and drug variables in a unified model to evaluate clinical outcomes.
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Enterobacteriaceae Resistentes a los Carbapenémicos , Infecciones por Klebsiella , Sepsis , Humanos , Klebsiella pneumoniae/genética , Colistina/farmacología , Colistina/uso terapéutico , Estudios Prospectivos , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Ceftazidima/farmacología , Ceftazidima/uso terapéutico , Compuestos de Azabiciclo/farmacología , Compuestos de Azabiciclo/uso terapéutico , Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Combinación de Medicamentos , Sepsis/tratamiento farmacológico , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/microbiologíaRESUMEN
Antimicrobial resistance (AMR) continues to spread at an alarming rate worldwide. Novel approaches are needed to mitigate its deleterious impact on antibiotic efficacy. Antibiotic stewardship aims to promote the appropriate use of antibiotics through evidence-based interventions. One paradigm is precision medicine, a medical model in which decisions, practices, interventions, and therapies are adapted to the individual patient based on their predicted response or risk of disease. Precision medicine approaches hold promise as a way to improve outcomes for patients with myriad illnesses, including infections such as bacteraemia and pneumonia. This review describes the latest advances in precision medicine as they pertain to antibiotic stewardship, with an emphasis on hospital-based antibiotic stewardship programmes. The impact of the COVID-19 pandemic on AMR and antibiotic stewardship, gaps in the scientific evidence, and areas for further research are also discussed.
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The COVID-19 pandemic has drawn considerable attention to viral pneumonia from clinicians, public health authorities, and the general public. With dozens of viruses able to cause pneumonia in humans, differentiating viral from bacterial pneumonia can be very challenging in clinical practice using traditional diagnostic methods. Precision medicine is a medical model in which decisions, practices, interventions, and therapies are adapted to the individual patient on the basis of their predicted response or risk of disease. Precision medicine approaches hold promise as a way to improve outcomes for patients with viral pneumonia. This review describes the latest advances in the use of precision medicine for diagnosing and treating viral pneumonia in adults and discusses areas where further research is warranted.
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COVID-19 , Neumonía Bacteriana , Neumonía Viral , Humanos , Pandemias , Neumonía Bacteriana/diagnóstico , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/terapia , Medicina de Precisión/métodosRESUMEN
Multidrug-resistant (MDR) Pseudomonas aeruginosa infections are a major clinical challenge. Many isolates are carbapenem resistant, which severely limits treatment options; thus, novel therapeutic combinations, such as imipenem-relebactam (IMI/REL), ceftazidime-avibactam (CAZ/AVI), ceftolozane-tazobactam (TOL/TAZO), and meropenem-vaborbactam (MEM/VAB) were developed. Here, we studied two extensively drug-resistant (XDR) P. aeruginosa isolates, collected in the United States and Mexico, that demonstrated resistance to IMI/REL. Whole-genome sequencing (WGS) showed that both isolates contained acquired GES ß-lactamases, intrinsic PDC and OXA ß-lactamases, and disruptions in the genes encoding the OprD porin, thereby inhibiting uptake of carbapenems. In one isolate (ST17), the entire C terminus of OprD deviated from the expected amino acid sequence after amino acid G388. In the other (ST309), the entire oprD gene was interrupted by an ISPa1328 insertion element after amino acid D43, rendering this porin nonfunctional. The poor inhibition by REL of the GES ß-lactamases (GES-2, -19, and -20; apparent Ki of 19 ± 2 µM, 23 ± 2 µM, and 21 ± 2 µM, respectively) within the isolates also contributed to the observed IMI/REL-resistant phenotype. Modeling of REL binding to the active site of GES-20 suggested that the acylated REL is positioned in an unstable conformation as a result of a constrained Ω-loop.
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Infecciones por Pseudomonas , Pseudomonas aeruginosa , Aminoácidos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Compuestos de Azabiciclo/farmacología , Compuestos de Azabiciclo/uso terapéutico , Combinación de Medicamentos , Humanos , Imipenem/farmacología , Imipenem/uso terapéutico , Pruebas de Sensibilidad Microbiana , Porinas/genética , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo , Estados Unidos , beta-Lactamasas/metabolismoRESUMEN
INTRODUCTION: Precision medicine is a medical model in which decisions, practices, interventions and therapies are tailored to the individual patient based on their predicted response or risk of disease. Sepsis is a life-threatening condition characterized by immune system dysregulation whose pathophysiology remains incompletely understood. There is much hope that precision medicine can lead to better outcomes in patients with sepsis. AREAS COVERED: In this review from a comprehensive literature search in PubMed for English-language studies in adults, we highlight recent advances in the diagnosis and treatment of sepsis of bacterial origin using precision medicine approaches including rapid diagnostic tests, predictive biomarkers, genomic methods, rapid antimicrobial susceptibility testing, and monitoring cell mediated immunity. Challenges and directions for future research are also discussed. EXPERT OPINION: Current diagnostic testing in sepsis relies primarily on conventional cultures (e.g. blood cultures), which are time-consuming and may delay critical therapeutic decisions. Nonculture-based techniques including nucleic acid amplification technologies (NAAT), other molecular methods (biomarkers), and genomic sequencing offer promise to overcome some of the inherent limitations seen with culture-based techniques.
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Medicina de Precisión , Sepsis , Biomarcadores , Humanos , Técnicas de Amplificación de Ácido Nucleico , Medicina de Precisión/métodos , Sepsis/diagnóstico , Sepsis/tratamiento farmacológicoRESUMEN
The diagnosis of a skin and soft tissue infection (SSTI) requires careful attention to a patient's history, physical examination, and diagnostic test results. We review for many bacterial, viral, fungal, and parasitic pathogens that cause SSTIs the clues for reaching a diagnosis, including reported past medical history, hobbies and behaviors, travel, insect bites, exposure to other people and to animals, environmental exposures to water, soil, or sand, as well as the anatomic site of skin lesions, their morphology on examination, and their evolution over time. Laboratory and radiographic tests are discussed that may be used to confirm a specific diagnosis.
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Enfermedades Cutáneas Infecciosas/diagnóstico , Infecciones de los Tejidos Blandos/diagnóstico , Absceso/diagnóstico , Animales , Celulitis (Flemón)/diagnóstico , Diagnóstico Diferencial , Exposición a Riesgos Ambientales/efectos adversos , Jardinería , Humanos , Uso Recreativo de Drogas , Factores de Riesgo , Conducta Sexual , Enfermedades Cutáneas Infecciosas/microbiología , Enfermedades Cutáneas Infecciosas/virología , Infecciones de los Tejidos Blandos/microbiología , Infecciones de los Tejidos Blandos/virología , Natación , Tatuaje/efectos adversos , ViajeAsunto(s)
Bacterias/genética , Farmacorresistencia Bacteriana Múltiple , Farmacorresistencia Fúngica Múltiple , Hongos/genética , Animales , Antiinfecciosos/farmacología , Antiinfecciosos/uso terapéutico , Bacterias/efectos de los fármacos , Centers for Disease Control and Prevention, U.S. , Hongos/efectos de los fármacos , Humanos , Estados UnidosRESUMEN
BACKGROUND: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome-coronavirus-2. Consensus suggestions can standardise care, thereby improving outcomes and facilitating future research. METHODS: An International Task Force was composed and agreement regarding courses of action was measured using the Convergence of Opinion on Recommendations and Evidence (CORE) process. 70% agreement was necessary to make a consensus suggestion. RESULTS: The Task Force made consensus suggestions to treat patients with acute COVID-19 pneumonia with remdesivir and dexamethasone but suggested against hydroxychloroquine except in the context of a clinical trial; these are revisions of prior suggestions resulting from the interim publication of several randomised trials. It also suggested that COVID-19 patients with a venous thromboembolic event be treated with therapeutic anticoagulant therapy for 3â months. The Task Force was unable to reach sufficient agreement to yield consensus suggestions for the post-hospital care of COVID-19 survivors. The Task Force fell one vote shy of suggesting routine screening for depression, anxiety and post-traumatic stress disorder. CONCLUSIONS: The Task Force addressed questions related to pharmacotherapy in patients with COVID-19 and the post-hospital care of survivors, yielding several consensus suggestions. Management options for which there is insufficient agreement to formulate a suggestion represent research priorities.
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Comités Consultivos/organización & administración , Betacoronavirus , Consenso , Infecciones por Coronavirus/epidemiología , Cooperación Internacional , Neumonía Viral/epidemiología , Neumología/normas , Sociedades Médicas , COVID-19 , Europa (Continente) , Humanos , Pandemias , SARS-CoV-2 , Estados UnidosRESUMEN
The effectiveness of antibiotics continues to erode because of the relentless spread of antimicrobial resistance (AMR). Public and private foundations, professional organizations, and international health agencies recognize the threat posed by AMR and have issued calls for action. One of the main drivers of AMR is overprescription of antibiotics, both in human and in veterinary medicine. The One Health concept is a response from a broad group of stakeholders to counter the global health threat posed by AMR. In this article, we discuss current trends in AMR and suggest strategies to mitigate its ongoing dissemination.
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Antiinfecciosos/economía , Farmacorresistencia Microbiana , Salud Única , Animales , Programas de Optimización del Uso de los Antimicrobianos , Centers for Disease Control and Prevention, U.S. , Prescripciones de Medicamentos , Salud Global , Producto Interno Bruto , Humanos , Estados UnidosRESUMEN
Community-acquired bacterial pneumonia (CABP) remains a significant cause of morbidity and mortality worldwide. Antimicrobial resistance, including in pathogens that cause CABP, continues to spread at an alarming rate. Because of these factors, the development of new antibiotic classes is urgently needed. Lefamulin, previously known as BC-3781, is a semisynthetic pleuromutilin antibiotic that was approved by the Food and Drug Administration for the treatment of CABP in adults. Available in both oral and intravenous formulations, lefamulin has potent in vitro activity against both typical and atypical CABP pathogens. The first pleuromutilin to be used systemically in humans, lefamulin has a unique mechanism of action that inhibits protein synthesis by preventing the binding of tRNA for peptide transfer. This review summarizes the available data on lefamulin, including recent evidence from 2 phase III clinical trials (LEAP 1 and LEAP 2), and discusses its potential role in the treatment of CABP.
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Infecciones Comunitarias Adquiridas , Neumonía Bacteriana , Compuestos Policíclicos , Adulto , Antibacterianos/uso terapéutico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Diterpenos , Humanos , Neumonía Bacteriana/tratamiento farmacológico , Tioglicolatos , PleuromutilinasRESUMEN
BACKGROUND: Predicting mortality risk in patients is important in research settings. The Pitt bacteremia score (PBS) is commonly used as a predictor of early mortality risk in patients with bloodstream infections (BSIs). We determined whether the PBS predicts 14-day inpatient mortality in nonbacteremia carbapenem-resistant Enterobacteriaceae (CRE) infections. METHODS: Patients were selected from the Consortium on Resistance Against Carbapenems in Klebsiella and Other Enterobacteriaceae, a prospective, multicenter, observational study. We estimated risk ratios to analyze the predictive ability of the PBS overall and each of its components individually. We analyzed each component of the PBS in the prediction of mortality, assessed the appropriate cutoff value for the dichotomized score, and compared the predictive ability of the qPitt score to that of the PBS. RESULTS: In a cohort of 475 patients with CRE infections, a PBS ≥4 was associated with mortality in patients with nonbacteremia infections (risk ratio [RR], 21.9; 95% confidence interval [CI], 7.0, 68.8) and with BSIs (RR, 6.0; 95% CI, 2.5, 14.4). In multivariable analysis, the hypotension, mechanical ventilation, mental status, and cardiac arrest parameters of the PBS were independent risk factors for 14-day all-cause inpatient mortality. The temperature parameter as originally calculated for the PBS was not independently associated with mortality. However, a temperature <36.0°C vs ≥36°C was independently associated with mortality. A qPitt score ≥2 had similar discrimination as a PBS ≥4 in nonbacteremia infections. CONCLUSIONS: Here, we validated that the PBS and qPitt score can be used as reliable predictors of mortality in nonbacteremia CRE infections.
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Bacteriemia , Infecciones por Enterobacteriaceae , Infecciones por Klebsiella , Antibacterianos/uso terapéutico , Bacteriemia/diagnóstico , Bacteriemia/tratamiento farmacológico , Carbapenémicos , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Humanos , Infecciones por Klebsiella/tratamiento farmacológico , Klebsiella pneumoniae , Estudios Prospectivos , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: We aimed to assess the knowledge, attitudes, and perceptions of resident physicians regarding sepsis in general and the Surviving Sepsis Campaign Guidelines in particular. METHODS: After institutional review board approval, we surveyed internal medicine (IM) and emergency medicine (EM) house staff from 3 separate institutions. House staff were notified of the survey via e-mail from their residency director or chief resident. The survey was Internet-based (using http://www.surveymonkey.com ), voluntary, and anonymous. The Surviving Sepsis Campaign Guidelines were used to develop the survey. The survey was open between December 2015 and April 2016. No incentives for participation were given. Reminder e-mails were sent approximately every 3 to 4 weeks to all eligible participants. Comparisons of responses were evaluated using the N-1 2-proportion test. RESULTS: A total of 133 responses were received. These included 84 from IM house staff, 27 from EM house staff, and 22 who selected "other." Eighty (101/126) percent reported managing at least 1 patient with sepsis in the preceding 30 days, 85% (97/114) rated their knowledge of the Surviving Sepsis Guidelines as "very familiar" or at least "somewhat familiar," and 84% (91/108) believed their training in the diagnosis and management of sepsis was "excellent" or at least "good." However, 43% (47/108) reported not receiving any feedback on their treatment of patients with sepsis in the last 30 days, while 24% (26/108) received feedback once. Both IM and EM house staff received comparable rates of feedback (62% vs 48%, respectively; P = .21). For the 3 questions that directly tested knowledge of the guidelines, the scores of the IM and EM house staff were similar. Notably, <20% of both groups correctly identified diagnostic criteria for sepsis. CONCLUSION: Additional education of IM and EM house staff on the Surviving Sepsis Campaign Guidelines is warranted, along with more consistent feedback regarding their diagnosis and management of sepsis.
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Cuidados Críticos/psicología , Conocimientos, Actitudes y Práctica en Salud , Médicos/psicología , Sepsis/psicología , Choque Séptico/psicología , Adulto , Cuidados Críticos/métodos , Medicina de Emergencia/métodos , Medicina de Emergencia/normas , Femenino , Promoción de la Salud , Humanos , Medicina Interna/métodos , Medicina Interna/normas , Internado y Residencia , Masculino , Guías de Práctica Clínica como Asunto , Sepsis/terapia , Choque Séptico/terapia , Encuestas y CuestionariosRESUMEN
Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) result in significant morbidity and mortality for patients in both community and health care settings. This is primarily due to the difficulty in treating MRSA, which is often resistant to multiple classes of antibiotics. Understanding the mechanisms of antimicrobial resistance (AMR) in MRSA provides insight into the optimal use of antimicrobial agents in clinical practice and also underpins critical aspects of antimicrobial stewardship programs. In this review we delineate the mechanisms, prevalence, and clinical importance of resistance to antibiotics licensed in the past 20 years that target MRSA, as well as new drugs in the pipeline which are likely to be licensed soon. Current gaps in scientific knowledge about MRSA resistance mechanisms are discussed, and topics in the epidemiology of AMR in S. aureus that require further investigation are highlighted.
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Omadacycline, an aminomethylcycline, is a novel member of the tetracycline class of antibiotics. It has received approval by the US Food and Drug Administration for the treatment of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections, and is available in both oral and intravenous formulations. It is also being evaluated in clinical trials for the treatment of cystitis and pyelonephritis. The omadacycline molecule was designed to overcome tetracycline resistance and has broad-spectrum activity that includes gram-positive bacteria, gram-negative bacteria, anaerobes, atypicals, and other drug-resistant strains, like methicillin-resistant Staphylococcus aureus, as well as Yersinia pestis and Bacillus anthracis, organisms of biodefense interest. Omadacycline has minimal drug-drug pharmacokinetic interactions and a favorable safety profile, with the most common adverse events being gastrointestinal symptoms.
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Bacterias/efectos de los fármacos , Infecciones Bacterianas/tratamiento farmacológico , Composición de Medicamentos , Tetraciclinas/química , Administración Intravenosa , Administración Oral , Ensayos Clínicos como Asunto , Farmacorresistencia Bacteriana , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Neumonía Bacteriana/tratamiento farmacológico , Tetraciclinas/efectos adversos , Tetraciclinas/farmacología , Tetraciclinas/uso terapéuticoRESUMEN
BACKGROUND: Fluoroquinolones are often prescribed unnecessarily and are an important risk factor for infection with fluoroquinolone-resistant gram-negative bacilli and Clostridioides difficile. METHODS: We conducted a quasi-experimental study to determine the impact of sequential syndrome-specific stewardship interventions on use of and resistance to fluoroquinolones in a tertiary care hospital. An initial 2-year intervention focused on reducing treatment of asymptomatic bacteriuria and ensuring concordance of urinary tract infection treatment with guidelines. A second 5-year intervention focused on limiting overuse of fluoroquinolones for health care-associated pneumonia in conjunction with a formal stewardship program. The primary outcomes were fluoroquinolone use and changes in use over time analyzed by segmented regression analysis. RESULTS: The asymptomatic bacteriuria and urinary tract infection intervention resulted in a significant reduction in fluoroquinolone use, with a significant change from an increasing to a decreasing rate of use (change in slope of quarterly defined daily doses/1,000 patient days -15.3, P < .01). The health care-associated pneumonia intervention resulted in a continued significant reduction in fluoroquinolone use (rate ratioâ¯=â¯0.68, P < .01). During the interventions, fluoroquinolone susceptibility increased significantly in Pseudomonas aeruginosa, but not in Escherichia coli, Klebsiella spp., or C difficile. CONCLUSIONS: Antimicrobial stewardship interventions focused on specific syndromes may be effective in reducing fluoroquinolone use. In our hospital, reduction in fluoroquinolone use resulted in increased fluoroquinolone susceptibility in P aeruginosa, but not other Enterobacteriaceae or C difficile.