piperacillin--tazobactam-drug-combination and Skin-Diseases--Infectious

Severe skin and soft-tissue infections (SSTIs), particularly diabetic foot infections, are a source of considerable morbidity and mortality. Inappropriate antimicrobial therapy may contribute to the increasing emergence of bacterial resistance, as well as to increased health care costs. Thus, there is a continuing search for reasonably safe, well-tolerated, and effective antimicrobial agents that are less susceptible to the development of resistance than older agents.. The Department of Veterans Affairs (VA) Medical Center in Nashville, Tennessee, was I site in a multicenter, Phase III, randomized, investigator-blinded clinical trial comparing the safety and efficacy of clinafloxacin with those of piperacillin/tazobactam in the treatment of adult patients with SSTI.. Over an 18-month period, patients aged > or = 18 years with physical findings of acute bacterial SSTI requiring hospitalization and intravenous antimicrobial therapy were randomized in a 1:1 ratio to receive either clinafloxacin 200 mg IV every 12 hours or piperacillin/tazobactam 3.375 g IV every 6 hours. After a minimum of 3 days of intravenous therapy, a switch to oral therapy with clinafloxacin 200 mg PO every 12 hours or amoxicillin/clavulanate 500 mg PO every 8 hours could be made in the respective treatment groups.. The center enrolled 84 patients (42 in each group), all but I of whom were male, reflecting the typical VA medical center population. The mean age was 60 years (range, 36-80 years) in the clinafloxacin group and 65 years (range, 35-87) in the piperacillin/tazobactam group; the latter group was significantly older (P = 0.0482), which could have affected recovery rates. Sixty-six patients were white and 18 were black. The mean ( +/- SD) duration of treatment was 10.69 +/- 5.34 days in the clinafloxacin group and 12.07 +/- 5.06 days in the piperacillin/tazobactam group; the mean length of stay was 10.83 +/- 10.28 days and 14.95 +/- 19.20 days, respectively. Fifty-three (63%) patients were switched to oral therapy (21 in the clinafloxacin group, 32 in the piperacillin/tazobactam group). The most commonly isolated pathogens were Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, and Enterobacter cloacae. Clinical cure rates and microbiologic eradication rates were similar between the 2 treatments. The piperacillin/ tazobactam arm experienced more all-cause adverse events than the clinafloxacin arm, although the difference was not statistically significant. The clinafloxacin arm experienced significantly more adverse events (eg, photosensitivity) that were judged by the investigator to be drug related (P = 0.034).. In this study population of hospitalized adults, clinafloxacin was as effective as piperacillin/tazobactam in the treatment of complicated SSTIs. Appropriate precautions must be taken against exposure to sunlight and ultraviolet light in patients receiving clinafloxacin, and adequate monitoring is necessary. Further investigation is necessary into how the phototoxic effects of the flu oroquinolones can be limited.

Topics: Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Dermatitis, Phototoxic; Double-Blind Method; Drug Therapy, Combination; Female; Fluoroquinolones; Hospitals, Veterans; Humans; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Skin Diseases, Infectious; Soft Tissue Infections; United States

Patients with skin and skin structure infections (SSTIs) and lower respiratory tract infections (LRTIs) are frequently prescribed piperacillin-tazobactam (TZP) on hospital admission. Inappropriate broad-spectrum coverage may be associated with patient harm, excess expenditure, and escalating rates of antimicrobial resistance.. Patients who received empirical TZP for a diagnosis of LRTI or SSTI from January 1-June 30, 2012, were identified retrospectively. Clinical and antimicrobial data were systematically collected from electronic hospital information systems. Using published guidelines, microbiologic results, and individual clinical responses, the appropriateness of TZP use was assessed. Drug utilization after potential standard audit of therapy on day 3 was also evaluated.. We reviewed 60 patients with SSTI and 169 patients with LRTI. Inappropriate empirical TZP therapy was found in 41.7% in those with SSTI, and a further 15% had inappropriate continuation of therapy. In LRTI patients, 38.3% received inappropriate empirical TZP, and 10.3% of the treatment courses were continued inappropriately. Community-acquired pneumonia was the most frequent diagnosis where TZP was used inappropriately (96%). A day 3 audit of therapy may have saved 256 days of TZP.. In our institution, inappropriate empirical TZP is common for community-onset infections of mild to moderate severity. A prospective audit and feedback program may be a strategy to reduce inappropriate use of TZP as empirical therapy.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Antimicrobial Stewardship; Cohort Studies; Community-Acquired Infections; Cross Infection; Drug Utilization; Female; Humans; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia; Retrospective Studies; Skin Diseases, Infectious; Soft Tissue Infections

The FDA recently issued guidance for the types of infections that should be included in trials to support an indication for antibacterial treatment. The latest FDA guidance recommends assessing response to drug therapy at 48 to 72 hours as the primary endpoint in clinical trials. This study evaluated clinical and economic outcomes among acute bacterial skin and skin structure infections (ABSSSI) patients hospitalized at a 3000-bed healthcare system in New Jersey.. In this retrospective cohort analysis, adult ABSSSI patients hospitalized between July 2010 and December 2011 were stratified based on infection type: cellulitis/erysipelas and major cutaneous abscess, wound infection, and all ABSSSI. Initial antibiotic therapy was assessed by individual agent, regimen, and MRSA coverage. Day 3 response to initial antibiotic therapy was evaluated based on temperature and lesion cessation outcomes; clinical response rates were assessed by initial therapy and pathogen for each cohort. The impact of response on length of stay (LOS), cost of care, and antibiotic treatment duration were also evaluated.. Commonly used antibiotics included vancomycin, cefazolin, piperacillin-tazobactam, and ampicillin-sulbactam; over 40% of patients received empiric therapy with activity against MRSA. Clinical non-response to initial antimicrobial therapy at Day 3 was 39.9%, 30.3%, and 60.7%, for all ABSSSI, cellulitis/abscess, and wound infection patients, respectively. The cost of care among non-responders was over 1.5 times that of responders (p < 0.0001). Non-response to initial therapy was associated with a 3.7 day increase in duration of antibiotic treatment (p < 0.0001).. Results of this study demonstrate that a significant percentage of ABSSSI patients, particularly those with wound infection, were not achieving clinical response at Day 3 of therapy. Failure to respond to drug therapy is associated with substantial increases in LOS, antibiotic treatment duration, and cost of care.. This had the inherent limitations associated with a retrospective chart review; because data was initially collected for clinical rather than research purposes, certain information may have been absent, incomplete, or missed by data abstractors.

Topics: Aged; Ampicillin; Anti-Bacterial Agents; Cefazolin; Female; Hospitalization; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Skin Diseases, Bacterial; Skin Diseases, Infectious; Sulbactam; Treatment Outcome; Vancomycin

We investigated knowledge, attitudes, and behaviors of prescribers concerning piperacillin-tazobactam use at 4 Emory University-affiliated hospitals. Discussions during focus groups indicated that the participants' perceived knowledge of clinical criteria for appropriate piperacillin-tazobactam use was inadequate. Retrospective review of medical records identified inappropriate practices. These findings have influenced ongoing interventions aimed at optimizing piperacillin-tazobactam use.

Topics: Anti-Bacterial Agents; Drug Utilization; Focus Groups; Health Knowledge, Attitudes, Practice; Hospitals, University; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Practice Guidelines as Topic; Practice Patterns, Physicians'; Skin Diseases, Infectious; Soft Tissue Infections