piperacillin--tazobactam-drug-combination and Soft-Tissue-Infections

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

Piperacillin-tazobactam is a beta-lactam/beta-lactamase inhibitor combination with a broad spectrum of antibacterial activity that includes Gram-positive and -negative aerobic and anaerobic bacteria. Piperacillin-tazobactam retains its in vitro activity against broad-spectrum beta-lactamase-producing and some extended-spectrum beta-lactamase-producing Enterobacteriaceae, but not against isolates of Gram-negative bacilli harboring AmpC beta-lactamases. Piperacillin-tazobactam has recently been reformulated to include ethylenediaminetetraacetic acid and sodium citrate; this new formulation has been shown to be compatible in vitro with the two aminoglycosides, gentamicin and amikacin, allowing for simultaneous Y-site infusion, but not with tobramycin. Multicenter, randomized, double-blinded clinical trials have demonstrated piperacillin-tazobactam to be as clinically effective as relevant comparator antibiotics. Clinical trials have demonstrated piperacillin-tazobactam to be effective for the treatment of patients with intra-abdominal infections, skin and soft tissue infections, lower respiratory tract infections, complicated urinary tract infections, gynecological infections and more recently, febrile neutropenia. Piperacillin-tazobactam has an excellent safety and tolerability profile and continues to be a reliable option for the empiric treatment of moderate-to-severe infections in hospitalized patients.

Topics: Anti-Bacterial Agents; beta-Lactamase Inhibitors; Clinical Trials as Topic; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Randomized Controlled Trials as Topic; Soft Tissue Infections

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

Piperacillin/tazobactam (P/T) or tazocin was used in the treatment of 40 patients with soft tissue purulent necrotic wounds of various genesis and localization. In the majority of the patients the affection was of recurring nature. P/T was administered in a dose of 4.5 g 3 times a day for 1 to 14 days (mainly for 8 to 10 days) as 30-minute intravenous infusions. The clinical effect of the treatment was stated in 36 patients (90 per cent). In 3 out of 8 patients with diabetes mellitus the treatment failed. In 1 patient the treatment was discontinued after the first dose because of asphyxia and a short-term decrease of the arterial pressure. Among 105 microbial strains isolated from 75 patients 64 were highly susceptible to P/T, 33 were moderately susceptible and 8 were resistant. 76.3 per cent of the isolates produced beta-lactamase, 66.3 per cent of them were susceptible to P/T. 54 gram-positive and gram-negative strains were isolated from 40 patients. 16 out of the 54 strains were isolated as monocultures and the others as associations. After the treatments the pathogen eradication and the pathogen eradication followed by superinfection were stated in 26 patients (66.7 per cent). In 11 patients (28.2 per cent) the pathogen persistence was observed at the background of the clinical improvement in the majority of the patients. The relapses were recorded in 2 patients (5.1 per cent).

Topics: Adolescent; Adult; Aged; beta-Lactamase Inhibitors; Drug Therapy, Combination; Female; Humans; Laboratories; Male; Microbial Sensitivity Tests; Middle Aged; Necrosis; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Recurrence; Soft Tissue Infections; Wound Infection

The SEP-1 measures have tied financial reimbursement to the treatment of patients with severe sepsis and septic shock. The purpose of this study was to assess the impact of a SEP-1 initiative on the utilization of broad-spectrum combination therapy (BSCT) in the emergency department (ED).. This was an IRB-approved, retrospective evaluation of adult patients who received vancomycin plus an antipseudomonal beta-lactam for a urinary tract infection (UTI) or skin or soft tissue infection (SSTI) in the ED. The primary outcome was the proportion of patients in which use of BSCT was considered appropriate based on clinical criteria. Secondary outcomes included door to antibiotic order time, door to administration time, proportion of patients continued on BSCT upon admission, duration of BSCT, and in-hospital mortality.. A total of 400 patients were included in the analysis. Following SEP-1 implementation, appropriate use of BSCT decreased by 12%, with 54% of patients in the pre-SEP-1 group meeting clinical criteria compared to 42% in the post-SEP-1 group (p = 0.028). In the subgroup of patients with a suspected UTI the appropriate use of BSCT declined by 25% (40% vs 15%, p = 0.005). The median door to first antibiotic administration time was not significantly different between groups (63 min vs 61 min, p = 0.091).. The implementation of the SEP-1 mandated measures was associated with an increase in the unnecessary use of BSCT. Additionally, no difference was seen in time to antibiotic administration. The results of this study demonstrate the negative impact that the SEP-1 mandate may have on antimicrobial utilization within the ED.

Topics: Adult; Aged; Anti-Bacterial Agents; Aztreonam; beta-Lactams; Cefepime; Centers for Medicare and Medicaid Services, U.S.; Early Diagnosis; Early Medical Intervention; Emergency Service, Hospital; Female; Guideline Adherence; Hospital Mortality; Hospitalization; Humans; Male; Medical Overuse; Meropenem; Middle Aged; Patient Care Bundles; Piperacillin, Tazobactam Drug Combination; Reimbursement Mechanisms; Retrospective Studies; Sepsis; Shock, Septic; Soft Tissue Infections; Time-to-Treatment; United States; Urinary Tract Infections; Vancomycin

Diabetic foot infections are a common and serious problem for all health systems worldwide. The aim of this study was to examine the resistance to antibiotics of microorganisms isolated from infected soft tissues of diabetic foot ulcers, using tissue cultures. We included 113 consecutive patients (70 men, 43 women) with a mean age of 66.4 ± 11.2 years and a mean diabetes duration of 14.4 ± 7.6 years presenting with diabetic foot soft tissue infections. Generally, no high antibiotic resistance was observed. Piperacillin-tazobactam exhibited the lowest resistance in Pseudomonas, as well as in the other Gram-negative pathogens. In methicillin-resistant Staphylococcus aureus isolates, there was no resistance to anti-Staphylococcus agents. Of note, clindamycin, erythromycin, and amoxycillin/clavulanic acid exhibited high resistance in Gram-positive cocci. These results suggest that antibiotic resistance in infected diabetic foot ulcers in our area is not high and they are anticipated to prove potentially useful in the initial choice of antibiotic regimen.

Topics: Aged; Anti-Bacterial Agents; Biological Availability; Diabetic Foot; Drug Resistance, Microbial; Female; Greece; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Patient Selection; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas; Soft Tissue Infections

We report a case of a rare complication of acute appendicitis with perforation through the abdominal wall. The case points out that an intraabdominal origin should be considered in patients presenting with rapidly spreading soft tissue infections of the trunk.. A 58-year-old European woman presented to our hospital with a 1-week history of severe abdominal pain accompanied by rapidly spreading erythema and emphysema of the lower abdomen. On admission, the patient was in septic shock with leukocytosis and elevation of C-reactive protein. Among other diagnoses, necrotizing fasciitis was suspected. Computed tomography showed a large soft tissue infection with air-fluid levels spreading through the lower abdominal wall. During the operation, we found a perforated appendicitis breaking through the fascia and causing a rapidly progressive soft tissue infection of the abdominal wall. Appendicitis was the origin of the soft tissue infection. The abdominal wall was only secondarily involved.. Even though perforated appendicitis as an etiology of a rapidly progressive soft tissue infection of the abdominal wall is very rare, it should be considered in the differential diagnosis of abdominal wall cellulitis. The distinction between rapidly spreading subcutaneous infection with abscess formation and early onset of necrotizing fasciitis is often difficult and can be confirmed only by surgical intervention.

Topics: Abdominal Pain; Abdominal Wall; Anti-Bacterial Agents; Appendectomy; Appendicitis; Emphysema; Escherichia coli Infections; Female; Humans; Middle Aged; Penicillanic Acid; Peritonitis; Piperacillin; Piperacillin, Tazobactam Drug Combination; Reoperation; Soft Tissue Infections; Tomography, X-Ray Computed; 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

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

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

The bactericidal exposures necessary for positive clinical outcomes among skin and soft tissue infections are largely dependent on interpatient pharmacokinetic variability and pathogen drug susceptibility. By simulating the probability of achieving target bactericidal exposures, the pharmacodynamics of three beta-lactam agents were compared against a range of pathogens implicated commonly in complicated skin and soft tissue infections.. Using Monte Carlo simulation, pharmacodynamic target attainment expressed as the percentage of the time interval during which the antibiotic concentration exceeded the minimal inhibitory concentration (%T > MIC) in serum and blister fluid was calculated for 5,000 simulated patients receiving imipenem-cilastatin 0.5 g q8h, meropenem 0.5 g q8h, piperacillin-tazobactam 3.375 g q6h, and piperacillin-tazobactam 4.5 g q8h. The pharmacokinetics for each antibiotic were derived from previously published healthy volunteer studies. The MICs for Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Enterobacter sp., Klebsiella sp., coagulase-negative staphylococci, Proteus sp., beta-hemolytic streptococci, and Serratia sp. were taken from the MYSTIC 2003 surveillance study and weighted by the prevalence of each pathogen among 1,404 isolates collected from skin and soft tissue infections during the 2000 SENTRY study. The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) was added into the model at increasing resistance rates.. Imipenem-cilastatin, meropenem, and piperacillin-tazobactam 3.375 g q6h achieved greater than 90% likelihood of achieving bactericidal exposure in serum and blister fluid until the prevalence of MRSA increased beyond 10%. Piperacillin-tazobactam 4.5 g q8h achieved a lower probability of achieving bactericidal exposure than the other regimens (88.7%, p < 0.001).. When the incidence of MRSA is low, imipenem-cilastatin, meropenem and piperacillin-tazobactam 3.375 g q6h would be optimal choices for the empiric treatment of complicated skin and soft tissue infections among the regimens studied. When MRSA is suspected, a drug that retains activity against this pathogen should be considered.

Topics: Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Dose-Response Relationship, Drug; Drug Combinations; Gram-Negative Bacteria; Gram-Positive Cocci; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Models, Biological; Monte Carlo Method; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Population Surveillance; Prevalence; Soft Tissue Infections; Thienamycins