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

Complicated skin and soft tissue infections (cSSTIs) are skin and soft tissue infections (SSTIs) that involve deep soft tissue. cSSTIs often require surgical intervention and/or hospitalization. cSSTIs are associated with significant mortality and morbidity, and carry a significant burden on health care systems. Piperacillin/tazobactam has been regarded as a standard treatment for cSSTIs because of its antibiotic spectrum, safety and clinical efficacy. Several antibiotics, as compared to piperacillin/tazobactam, have been evaluated in the treatment of cSSTIs. Areas covered: This review summarizes randomized controlled trials (RCTs) evaluating the clinical efficacy of piperacillin/tazobactam for the treatment of cSSTIs. Expert opinion: Piperacillin/tazobactam, which covers most causative organisms in cSSTIs, is the drug of choice for the treatment of cSSTIs. Other options such as ertapenem and moxifloxacin may be reasonable where multiple daily dosing or intravenous administration is inappropriate. But in general, they should be avoided as an empirical treatment because of their highly association with resistant bacteria, which are becoming a global threat. Therefore, piperacilin/tazobactam is appropriate as an empirical therapy for the treatment of SSTIs and should be de-escalated as soon as causative organisms are identified, their drug-sensitivity results are available, and clinical condition becomes stable.

Topics: Anti-Bacterial Agents; Drug Therapy, Combination; Fluoroquinolones; Humans; Moxifloxacin; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Randomized Controlled Trials as Topic; Skin Diseases, Bacterial; Soft Tissue Infections; Treatment Outcome

The primary aim of the RELIEF study was to evaluate the efficacy and safety of two sequential intravenous (iv)/oral regimens: moxifloxacin iv/oral versus piperacillin/tazobactam (TZP) iv followed by oral amoxicillin/clavulanate (AMC).. The study had a prospective, randomized, double-dummy, double-blind, multicentre design. Patients ≥18 years were prospectively stratified according to complicated skin and skin structure infection (cSSSI) subtype/diagnosis (major abscess, diabetic foot infection, wound infection or infected ischaemic ulcer), surgical intervention and severity of illness. Diagnoses and disease severity were based on predetermined criteria, documented by repeated photographs, and confirmed by an independent data review committee. Patients were randomized to receive either 400 mg of moxifloxacin iv once daily followed by 400 mg of moxifloxacin orally once daily or 4.0/0.5 g of TZP iv thrice daily followed by 875/125 mg of AMC orally twice daily for 7-21 days. The primary efficacy variable was clinical response at test of cure (TOC) for the per-protocol (PP) population. Clinical efficacy was assessed by the data review committee based on repeated photographs and case descriptions. Clinical trials registry number: NCT 00402727.. A total of 813 patients were randomized. Clinical success rates at TOC were similar for moxifloxacin and TZP-AMC in the PP [320/361 (88.6%) versus 275/307 (89.6%), respectively; P = 0.758] and intent-to-treat (ITT) [350/426 (82.2%) versus 305/377 (80.9%), respectively; P = 0.632] populations. Thus, moxifloxacin was non-inferior to TZP-AMC. Bacteriological success rates were high in both treatment arms [moxifloxacin: 432/497 (86.9%) versus TZP-AMC: 370/429 (86.2%), microbiologically valid (MBV) population]. Moxifloxacin was non-inferior to TZP-AMC at TOC in both the MBV and the ITT populations. Both treatments were well tolerated.. Once-daily iv/oral moxifloxacin monotherapy was clinically and bacteriologically non-inferior to iv TZP thrice daily followed by oral AMC twice daily in patients with cSSSIs.

Topics: Adult; Aged; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Aza Compounds; Double-Blind Method; Drug Therapy, Combination; Female; Fluoroquinolones; Humans; Male; Middle Aged; Moxifloxacin; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Quinolines; Skin; Skin Diseases, Bacterial

In this prospective, double-blind, multicentre trial, adult patients with complicated skin and skin structure infection (cSSSI) randomly received sequential intravenous (i.v.)/oral (p.o.) moxifloxacin (400 mg once a day) or a control regimen of i.v. piperacillin-tazobactam (3.0/0.375 g every 6 h) followed by p.o. amoxicillin-clavulanate (800 mg every 12 h), each for 7-14 days. Clinical cure rates at the test-of-cure visit (10-42 days post therapy) for the efficacy-valid population were 79% (143/180) for the moxifloxacin-treated group and 82% (153/187) for the control group (95% confidence interval, -12.04, 3.29). Bacteriological eradication rates for Staphylococcus aureus, the most prevalent organism, were 78% and 80%, respectively. The incidence of drug-related adverse events was similar for both groups (31% moxifloxacin, 30% control). Sequential i.v./p.o. moxifloxacin was as effective and well tolerated as i.v. piperacillin-tazobactam followed by p.o. amoxicillin-clavulanate in treating patients with cSSSI.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Aza Compounds; Double-Blind Method; Drug Administration Schedule; Drug Resistance, Bacterial; Drug Tolerance; Female; Fluoroquinolones; Humans; Injections, Intravenous; Male; Middle Aged; Moxifloxacin; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Quinolines; Safety; Skin Diseases, Bacterial

The efficacy of ertapenem 1 g once a day for the treatment of polymicrobial complicated intra-abdominal, complicated skin/skin-structure and acute pelvic infections was compared with piperacillin-tazobactam 3.375 g every 6 h in a post hoc analysis of data from three large randomized double-blind trials. Of the 1,558 treated patients in the three trials, no pathogen was identified in 345 (22.1%), 423 (27.2%) had a monomicrobial infection and 790 (50.7%) had a polymicrobial infection. At the test-of-cure assessment, there were no significant differences in outcome between the two treatment groups for any of the three infections. Cure rates (clinical and microbiological for intra-abdominal infection, clinical for skin/skin-structure and pelvic infections) in microbiologically evaluable patients for ertapenem and piperacillin-tazobactam, respectively, were 85.6% (154/180 evaluable patients) and 82.5% (127/154) for polymicrobial intra-abdominal infection, 80.3% (53/66) and 78.7% (48/61) for polymicrobial skin/skin-structure infection, and 95.7% (88/92) and 92.6% (88/95) for polymicrobial pelvic infection. Respective cure rates for all evaluable patients in the original trials were: 83.6% and 80.4% for intra-abdominal, 83.9% and 85.3% for skin/skin-structure, and 93.9% and 91.5% for pelvic infections. These data show that in the three trials, ertapenem 1 g once a day was highly effective for the treatment of polymicrobial infections and as effective as piperacillin-tazobactam 3.375 g every 6 h.

Topics: Abdomen; Adolescent; Adult; Anti-Bacterial Agents; Bacteria, Aerobic; Bacteria, Anaerobic; Bacterial Infections; beta-Lactams; Double-Blind Method; Ertapenem; Female; Humans; Lactams; Male; Pelvic Infection; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Skin Diseases, Bacterial; Treatment Outcome

Staphylococcus aureus is the predominant pathogen in complicated skin/skin structure infections. In this analysis of a subgroup of data from a randomised, double-blind trial, the efficacy of ertapenem 1 g daily was compared with piperacillin-tazobactam 3.375 g Q6H for treatment of complicated skin/skin structure infections caused by methicillin-susceptible S. aureus (MSSA). Of the 529 treated patients in this trial, 185 (35.0%) had MSSA as a baseline pathogen. At the test of cure assessment 10-21 days post-therapy, 54 of 67 (80.6%) protocol evaluable patients in the ertapenem group and 55 of 68 (80.9%) in the piperacillin-tazobactam group were cured (odds ratio: 1.0 (95% confidence interval (CI): 0.4-2.4), P = 0.99). In both treatment groups, cure rates were higher in patients with monomicrobial than polymicrobial infections, but the difference was not significant. In this subgroup analysis of patients with MSSA complicated skin/skin structure infections, therapy with ertapenem 1 g daily was as effective as piperacillin-tazobactam 13.5 g divided in four daily doses.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactams; Double-Blind Method; Ertapenem; Female; Humans; Lactams; Male; Methicillin Resistance; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Skin Diseases, Bacterial; Staphylococcal Infections; Staphylococcus aureus

Anaerobes are an important component of many serious, deep tissue infections, especially complicated intra-abdominal (IAI), complicated skin and skin structure (SSSI), and acute pelvic (PI) infections. This study compares the efficacy of ertapenem, 1 g once a day, in the treatment of adults with anaerobic IAI, SSSI, and PI to piperacillin-tazobactam, 3.375 g every 6 hours.. Three randomized, double-blind trials comparing ertapenem to piperacillin-tazobactam for treatment of IAI, SSSI, and PI were conducted. This subgroup analysis included 623 patients, whose baseline culture grew one or more anaerobic pathogens, from these three studies.. Anaerobes most commonly isolated were Bacteroides fragilis group (IAI) and peptostreptococci (SSSI and PI). The median duration of ertapenem and piperacillin-tazobactam therapy, respectively, in these subgroups was 6 and 7 days for IAI, 7 and 8 days for SSSI, and 4 and 5 days for PI. Cure rates for all evaluable patients with anaerobic infection were 89.3% (242/271) for ertapenem and 85.9% (220/256) for piperacillin-tazobactam (95% CI for the difference, adjusting for infection, -2.6% to 9.3%), indicating that the two treatments were equivalent. Cure rates by infection, for ertapenem and piperacillin-tazobactam, respectively, were as follows: IAI, 86.4% (133/154) and 82.4% (117/142); SSSI, 84.4% (27/32) and 82.4% (28/34); PI, 96.5% (82/85) and 93.8% (75/80). The frequency and severity of drug-related adverse experiences were comparable in both treatment groups.. In this subgroup analysis, ertapenem was as effective as piperacillin-tazobactam for treatment of adults with moderate to severe anaerobic IAI, SSSI, and PI, was generally well tolerated, and had a similar safety profile.

Topics: Abdomen; Adult; Aged; Anti-Bacterial Agents; Bacteria, Anaerobic; Bacterial Infections; beta-Lactams; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Ertapenem; Female; Humans; Lactams; Male; Middle Aged; Pelvic Infection; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Skin Diseases, Bacterial; Surgical Wound Infection

The pathogenicity of Enterococcus in polymicrobial surgical infections is controversial. The objective of this analysis was two-fold. The impact of Enterococcus on clinical outcome was assessed in adults with complicated intra-abdominal (IAI), complicated skin and skin structure (CSSSI), or acute pelvic (PI) infection treated with ertapenem or piperacillin-tazobactam, which is more active in vitro against enterococci than ertapenem. Baseline characteristics were identified that were associated with Enterococcus infection and with treatment failure.. This analysis included 1,558 patients treated in three randomized, triple-blind studies. Of these patients, 223 had Enterococcus in initial cultures: 125 of 623 (20%) with IAI, 28 of 529 (5%) with CSSSI, and 70 of 406 (17%) with PI. Logistic regression models were fit to assess each objective.. The cure rates for the two treatment groups were similar in each of the three studies, regardless of the presence or absence of Enterococcus. Cure rates for both treatment groups combined were significantly lower in patients with Enterococcus than without Enterococcus for IAI (76% [69/91] versus 87% [264/305], OR 2.3 [95% CI, 1.2-4.1], P = 0.009) and CSSSI (58% [11/19] versus 84% [241/287], OR 3.8 [95% CI, 1.5-10.0], P = 0.010); but for PI, rates were similar (96% [50/52] versus 92% [188/205], OR 0.4 [95% CI, 0.1-1.9], P = 0.220). Characteristics predictive of the presence of Enterococcus were Pseudomonas aeruginosa as a baseline pathogen for IAI, older age, and the presence of a complicating underlying disease for CSSSI, and infection severity rated moderate rather than severe for PI. The strongest predictors of treatment failure were >2 days postoperative infection at study entry for patients with IAI and older age for patients with CSSSI.. Choice of antimicrobial therapy did not affect cure rates in patients with or without Enterococcus. The strongest predictors of failure were postoperative infection at study entry in patients with IAI and older age in patients with CSSSI.

Topics: Abdomen; Adolescent; Adult; Aged; Anti-Bacterial Agents; beta-Lactams; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Enterococcus; Ertapenem; Female; Gram-Positive Bacterial Infections; Humans; Lactams; Male; Middle Aged; Pelvic Infection; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Skin Diseases, Bacterial; Surgical Wound Infection; Treatment Outcome

A recent, frequently quoted study has suggested that for bloodstream infections (BSIs) due to extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL) Escherichia coli, treatment with β-lactam/β-lactamase inhibitors (BLBLIs) might be equivalent to treatment with carbapenems. However, the majority of BSIs originate from the urinary tract. A multicenter, multinational efficacy analysis was conducted from 2010 to 2012 to compare outcomes of patients with non-urinary ESBL BSIs who received a carbapenem (69 patients) vs those treated with piperacillin-tazobactam (10 patients). In multivariate analysis, therapy with piperacillin-tazobactam was associated with increased 90-day mortality (adjusted odds ratio, 7.9, P=.03). For ESBL BSIs of a non-urinary origin, carbapenems should be considered a superior treatment to BLBLIs.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Carbapenems; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Hospital Mortality; Humans; Intraabdominal Infections; Length of Stay; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Skin Diseases, Bacterial; 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