piperacillin--tazobactam-drug-combination and Bacterial-Infections

Piperacillin/tazobactam or meropenem are often used to treat patients with severe bacterial infections. We aimed to compare the desirable and undesirable effects of empirical and/or definitive piperacillin/tazobactam versus carbapenems in patients with severe bacterial infections.. We searched PubMed, Embase, CENTRAL, Epistemonikos, and trial registers for randomised clinical trials of empirical and/or definitive piperacillin/tazobactam versus carbapenems in adult patients with severe bacterial infection (i.e., any bacterial infection requiring hospitalisation). The primary outcome was all-cause short-term mortality within 90 days. Secondary outcomes were all-cause long-term mortality, adverse events, quality of life, days alive without or duration of life support, secondary infections, selection of fungi or resistant bacteria, and days alive and out of hospital or hospital length of stay. We calculated relative risks (RRs) using random effects and fixed effect meta-analyses along with trial sequential analyses.. We included 31 trials (n = 8790 patients) with overall high risk of bias. The RR for all-cause short-term mortality was 1.16 (95% confidence interval [CI]: 0.94-1.43, low certainty evidence), for adverse events 1.00 (98% CI: 0.96-1.04, moderate certainty evidence), for secondary infections 1.13 (98% CI: 0.76-1.68, very low certainty evidence), and for selection of fungi or resistant bacteria 1.61 (98% CI: 0.89-2.89, very low certainty evidence). There were no or limited data for the remaining outcomes.. Based on very low or low certainty evidence, piperacillin/tazobactam may be associated with less favourable outcomes in patients with severe bacterial infections as compared with carbapenems, but the information size for a robust conclusion has not been reached.

Topics: Adult; Bacteria; Bacterial Infections; Carbapenems; Coinfection; Humans; Piperacillin, Tazobactam Drug Combination; Quality of Life

Beta-lactam dose optimization in critical care is a current priority. We aimed to review the pharmacokinetics (PK) of three commonly used beta-lactams (amoxicillin ± clavulanate, piperacillin-tazobactam and meropenem) to compare PK parameters reported in critically and noncritically ill neonates, children and adults, and to investigate whether allometric and maturation scaling principles could be applied to describe changes in PK parameters through life.. A systematic review of PK studies of the three drugs was undertaken using MEDLINE and EMBASE. PK parameters and summary statistics were extracted and scaled using allometric principles to 70 kg individual for comparison. Pooled data were used to model clearance maturation and decline using a sigmoidal (Hill) function.. A total of 130 papers were identified. Age ranged from 29 weeks to 82 years and weight from 0.9-200 kg. PK parameters from critically ill populations were reported with wider confidence intervals than those in healthy volunteers, indicating greater PK variability in critical illness. The standard allometric size and sigmoidal maturation model adequately described increasing clearance in neonates, and a sigmoidal model was also used to describe decline in older age. Adult weight-adjusted clearance was achieved at approximately 2 years postmenstrual age. Changes in volume of distribution were well described by the standard allometric model, although amoxicillin data suggested a relatively higher volume of distribution in neonates.. Critical illness is associated with greater PK variability than in healthy volunteers. The maturation models presented will be useful for optimizing beta-lactam dosing, although a prospective, age-inclusive study is warranted for external validation.

Topics: Adult; Age Factors; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacterial Infections; beta-Lactamase Inhibitors; Biological Variation, Population; Child; Critical Illness; Dose-Response Relationship, Drug; Healthy Volunteers; Humans; Infant, Newborn; Meropenem; Microbial Sensitivity Tests; Piperacillin, Tazobactam Drug Combination

Bacterial peritonitis, an infection of the ascitic fluid, can be classified etiologically as spontaneous or secondary bacterial peritonitis. The former is mainly caused by portal hypertension and its subsequent effects, whereas the latter is caused by the direct dissemination of bacteria into the peritoneal cavity. Previous reports have described some distinguishing features of these two entities. Here, we report the first known case of bacterial peritonitis with Aeromonas hydrophilia and Escherichia coli in a patient with malignant ascites associated with pancreatic carcinoma who exhibited features of both spontaneous and secondary peritonitis. Our report suggests that clinicians should also consider bacterial peritonitis in patients with malignant ascites who present with ostensibly cancer-related symptoms.

Topics: Aeromonas hydrophila; Anti-Bacterial Agents; Ascites; Ascitic Fluid; Bacterial Infections; Drainage; Escherichia coli; Humans; Male; Middle Aged; Pancreatic Neoplasms; Peritonitis; Piperacillin, Tazobactam Drug Combination; Tomography, X-Ray Computed

Early empirical broad-spectrum antimicrobial therapy is recommended for patients with severe infections, including sepsis. β-lactam/β-lactamase inhibitor combinations or carbapenems are often used to ensure coverage of likely pathogens. Piperacillin/tazobactam is proposed as a carbapenem-sparing agent to reduce the incidence of multidrug-resistant bacteria and superinfections. In the recently published MERINO trial, increased mortality from piperacillin/tazobactam was suggested in patients with bacteraemia with resistant Escherichia coli or Klebsiella species. Whether these findings also apply to empirical piperacillin/tazobactam in patients with other severe infections, including sepsis, is unknown. We aim to assess the benefits and harms of empirical and definitive piperacillin/tazobactam vs carbapenems for patients with severe bacterial infections.. This protocol has been prepared according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols statement, the Cochrane Handbook and the Grading of Recommendations, Assessment, Development, and Evaluation approach. We will include randomised clinical trials assessing piperacillin/tazobactam vs carbapenems in patients with severe bacterial infections of any origin. The primary outcome will be all-cause short-term mortality ≤ 90 days. Secondary outcomes will include all-cause long-term mortality > 90 days, adverse events, quality of life, use of life support, secondary infections, antibiotic resistance, and length of stay. We will conduct meta-analyses, including pre-planned subgroup and sensitivity analyses for all assessed outcomes. The risk of random errors in the meta-analyses will be assessed by trial sequential analysis.

Topics: Anti-Bacterial Agents; Bacterial Infections; Carbapenems; Drug Resistance, Multiple, Bacterial; Humans; Piperacillin, Tazobactam Drug Combination

Piperacillin-tazobactam is a commonly used antibiotic in critically ill patients; however, controversy exists as to whether mortality in serious infections can be decreased through administration by prolonged infusion compared with intermittent infusion. The purpose of this systematic review and meta-analysis was to describe the impact of prolonged infusion piperacillin-tazobactam schemes on clinical endpoints in severely ill patients.. We conducted a systematic literature review and meta-analysis searching MEDLINE, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library from inception to April 1, 2017, for studies.. Mortality rates were compared between severely ill patients receiving piperacillin-tazobactam via prolonged infusion or intermittent infusion. Included studies must have reported severity of illness scores, which were transformed into average study-level mortality probabilities.. Two investigators independently screened titles, abstracts, and full texts of studies meeting inclusion criteria for this systematic review and meta-analysis. Variables included author name, publication year, study design, demographics, total daily dose(s), average estimated creatinine clearance, type of prolonged infusion, prevalence of combination therapy, severity of illness scores, infectious sources, all-cause mortality, clinical cure, microbiological cure, and hospital and ICU length of stay. The review identified 18 studies including 3,401 patients who received piperacillin-tazobactam, 56.7% via prolonged infusion. Across all studies, the majority of patients had an identified primary infectious source. Receipt of prolonged infusion was associated with a 1.46-fold lower odds of mortality (95% CI, 1.20-1.77) in the pooled analysis. Patients receiving prolonged infusion had a 1.77-fold higher odds of clinical cure (95% CI, 1.24-2.54) and a 1.22-fold higher odds of microbiological cure (95% CI, 0.84-1.77). Subanalyses were conducted according to high (≥ 20%) and low (< 20%) average study-level mortality probabilities. In studies reporting higher mortality probabilities, effect sizes were variable but similar to the pooled results.. Receipt of prolonged infusion of piperacillin-tazobactam was associated with reduced mortality and improved clinical cure rates across diverse cohorts of severely ill patients.

Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Administration Schedule; Humans; Infusions, Intravenous; Piperacillin, Tazobactam Drug Combination; Severity of Illness Index; Time Factors; Treatment Outcome

To prevent the devastating consequences of infection, most infants admitted to the neonatal intensive care unit are exposed to antibiotics. However, dosing regimens are often extrapolated from data in adults and older children, increasing the risk for drug toxicity and lack of clinical efficacy because they fail to account for developmental changes in infant physiology. However, newer technologies are emerging with minimal-risk study designs, including ultra-low-volume assays, pharmacokinetic modeling and simulation, and opportunistic drug protocols. With minimal-risk study designs, pharmacokinetic data and dosing regimens for infants are now available for ampicillin, clindamycin, meropenem, metronidazole, and piperacillin/tazobactam.

Topics: Ampicillin; Anti-Bacterial Agents; Bacterial Infections; Clindamycin; Humans; Infant; Infant, Newborn; Infant, Premature; Intensive Care Units, Neonatal; Meropenem; Metronidazole; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Practice Guidelines as Topic; Thienamycins

Piperacillin/Tazobactam is a time-dependent antimicrobial combination (beta-lactam/beta-lactamase inhibitor) commonly used in the treatment of severe Gram-negative infections. The optimisation of its time-dependent bactericidal activity via continuous infusion could improve clinical outcomes. Several studies have been realized on the relevance of a continuous infusion, but, to date, no definitive position can be adopted on the matter and a well-designed randomized controlled trial is warranted. In other articles, continuous infusion regimens are also more cost efficient. This article is an update, including the most recent trials about this subject.

Topics: Anti-Bacterial Agents; Bacterial Infections; beta-Lactamase Inhibitors; Drug Costs; Drug Stability; Humans; Infusions, Intravenous; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

Piperacillin-tazobactam is a frequently prescribed intravenous antibiotic for moderate to severe infections used in hospital settings because of its broad activity against many pathogenic bacteria including Pseudomonas aeruginosa. However, its pharmacokinetics (PK) can be significantly altered in a variety of states.. This article provides a comprehensive and critical review of the PK of piperacillin-tazobactam in different patient populations. The pharmacodynamics (PD) of piperacillin-tazobactam is also discussed.. The importance of appropriate antibiotic dosing in the context of the global tendency for reduced susceptibility of bacteria, including P. aeruginosa is emphasized. The interrelationship between PK and PD is discussed to provide an understanding of methods for procuring dosing regimens that increase the likelihood of clinical success for individual patients. Alternative dosing regimens, which may include administration by extended or continuous infusion of piperacillin-tazobactam as a mechanism to increase the likelihood of pharmacodynamic target attainment, are described.. Where piperacillin-tazobactam is required for treatment, applying knowledge of PK and PD characteristics can facilitate optimal outcomes.

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Administration Schedule; Humans; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Treatment Outcome

Topics: Adult; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Child; Clinical Trials as Topic; Drug Resistance, Bacterial; Humans; Injections, Intravenous; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

The authors had for aim to assess the effectiveness and toxicity of a piperacillin-tazobactam-netilmicin combination, and the possibility of avoiding using glycopeptide, in children with febrile neutropenic episodes induced by chemotherapy.. A retrospective study was made, including children treated for a febrile neutropenic episode (absolute neutrophile count < 0.5 x 10(9)/l) by a piperacillin-tazobactam-netilmicin combination. If fever persisted 48 hours after the beginning of antibiotic therapy, a glycopeptide could be added. The responses to the treatment were defined as follows: 1) total success (no fever or documented infection) at 48 hours and at 72 hours following the beginning of treatment; 2) partial success (apyrexia beyond 72 hours without any therapeutic change); 3) failure (persistent infectious signs 48 hours after the introduction of glycopeptide).. Sixty-nine episodes were assessable, corresponding to 41 patients, treated for a solid tumour (29), an acute leukaemia in remission (11), or a metabolic disease (1). The febrile episodes were divided into fever of unknown origin (71%), microbiologically documented fever (12%), and clinically documented fever (17%). No death occurred, no toxicity was reported. With this antibiotic therapy, total success at 72 hours was observed in 72% in case of fever of unknown origin and 45% in case of documented infections. The success rate reached 84% when a glycopeptide was added (30% of the cases).. The piperacillin-tazobactam-netilmicin combination is very effective and well tolerated in probabilistic treatment of febrile neutropenia induced by chemotherapy, but does not allow to decreasing the frequency of glycopeptide administration.

Topics: Adolescent; Anti-Bacterial Agents; Antineoplastic Agents; Bacterial Infections; Child; Child, Preschool; Clinical Trials as Topic; Drug Combinations; Drug Evaluation; Escherichia coli Infections; Female; Fever; Fever of Unknown Origin; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Infant; Male; Neoplasms; Netilmicin; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Postoperative Complications; Retrospective Studies; Treatment Outcome; Urinary Tract Infections

Ertapenem is a Group 1 carbapenem that was licensed in the USA in November 2001 and in Europe in April 2002. Its safety profile has been assessed in 240 healthy volunteers participating in 12 clinical pharmacology studies and in 2046 patients enrolled in five Phase IIa and eight Phase IIb/III clinical trials. The most common drug-related adverse events (AEs) reported in trials comparing ertapenem and piperacillin-tazobactam and in trials comparing ertapenem and ceftriaxone were: diarrhoea (ertapenem versus piperacillin-tazobactam 5.0% versus 7.0%; ertapenem versus ceftriaxone 5.6% versus 5.9%); infused vein complications (ertapenem versus piperacillin-tazobactam 4.5% versus 7.9%; ertapenem versus ceftriaxone 3.2% versus 4.6%); nausea (ertapenem versus piperacillin-tazobactam 2.5% versus 3.4%; ertapenem versus ceftriaxone 3.4% versus 3.3%); and elevations in alanine aminotransferase levels (ertapenem versus piperacillin-tazobactam 8.8% versus 7.3%; ertapenem versus ceftriaxone 8.3% versus 6.9%). Most ertapenem-related AEs were reported as mild-to-moderate in intensity. Ertapenem was not associated with prolongation of the QTc interval. Local reactions of moderate-to-severe intensity at the infusion site were infrequent and occurred with similar frequency in the ertapenem and comparator treatment groups. No overall differences in safety were observed between elderly (aged > or = 65 years and > or = 75 years) and younger patients. Ertapenem, 1 g once a day given by intravenous infusion or intramuscular injection, was generally well tolerated and had overall safety and tolerability profiles similar to those of piperacillin-tazobactam and ceftriaxone.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteria, Aerobic; Bacteria, Anaerobic; Bacterial Infections; beta-Lactams; Ceftriaxone; Clinical Trials as Topic; Community-Acquired Infections; Ertapenem; Female; Humans; Lactams; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Randomized Controlled Trials as Topic

Piperacillin/tazobactam is a beta-lactam/beta-lactamase inhibitor combination with a broad spectrum of antibacterial activity against most Gram-positive and Gram-negative aerobic bacteria and anaerobic bacteria. Piperacillin/tazobactam is effective and well-tolerated in patients with lower respiratory tract infections (LRTI), intra-abdominal infections, skin and soft tissue infections, and febrile neutropenia. In comparative clinical trials against various other antibacterial regimens, piperacillin/tazobactam has shown higher clinical success rates, particularly in the treatment of patients with intra-abdominal infections and febrile neutropenia. Cost analyses of piperacillin/tazobactam have been variable, in part, because of differences in specific costs included. Three US cost analyses found that piperacillin/tazobactam had lower total medical costs than clindamycin plus gentamicin or imipenem/cilastatin in intra-abdominal infections, and ticarcillin/ clavulanic acid in community-acquired pneumonia. Piperacillin/tazobactam plus amikacin had lower total costs than ceftazidime plus amikacin in another cost analysis of patients with febrile neutropenic episodes modelled in nine European countries. However, piperacillin/tazobactam plus tobramycin was more costly than ceftazidime plus tobramycin in hospital-acquired pneumonia in a US cost analysis. In cost-effectiveness analyses, all studies of intra-abdominal infections, pneumonia and febrile neutropenic episodes consistently reported lower costs per unit of effectiveness versus comparators. Piperacillin/tazobactam was dominant (greater efficacy and lower costs) versus imipenem/cilastatin in intra-abdominal infections and ceftriaxone, ciprofloxacin or meropenem in pneumonia. Piperacillin/tazobactam plus amikacin was dominant over ceftazidime plus amikacin in the treatment of febrile neutropenic episodes. In a cost-effectiveness analysis of skin and soft tissue infection, piperacillin/tazobactam had lower costs per successfully treated patient than ceftriaxone or cefotaxime, but a slightly higher cost-effectiveness ratio than amoxicillin/clavulanic acid. All cost-effectiveness analyses were based on decision-analytical models.. Piperacillin/tazobactam is likely to reduce overall treatment costs of moderate to severe bacterial infections by increasing initial treatment success, thereby reducing the length of hospital stay and the use of additional antibacterials. Piperacillin/tazobactam has shown clinical and economic advantages over standard antibacterial regimens in the treatment of intra-abdominal infections, LRTIs, febrile episodes in patients with neutropenia, and skin and soft tissue infections, although more complete published data are needed to confirm these results. Present data regarding clinical efficacy, bacterial resistance and costs would support the use of piperacillin/tazobactam as an empirical first-line option in moderate to severe bacterial infections.

Topics: Bacterial Infections; Cost-Benefit Analysis; Cross Infection; Drug Therapy, Combination; Drug Tolerance; Economics, Pharmaceutical; Hospitalization; Humans; Microbial Sensitivity Tests; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

Broad-spectrum beta-lactam antibiotics have several advantages in the treatment of intra-abdominal infections. These agents are effective against gram-negative rods and anaerobes, reach therapeutic levels rapidly after parenteral administration, and, in the absence of penicillin allergy, generally exhibit low toxicity. The second-generation cephalosporins (e.g., cefoxitin, cefotetan) are used widely in surgical prophylaxis, trauma, and treatment of mild-to-moderate community-acquired infections, but limitations in their spectra and microbial resistance restrict their utility in more serious infections. Extended-spectrum penicillin/beta-lactamase-inhibitor combinations are effective in the treatment of intra-abdominal infections and include enterococci in their spectrum. Gram-negative aerobe resistance has developed to ampicillin/sulbactam. Piperacillin/tazobactam, a ureidopenicillin with increased gram-negative coverage and enhanced antipseudomonal activity, has proved to be effective in clinical trial therapy for intra-abdominal infections. The very broad spectrum carbapenems--imipenem/cilastatin and meropenem--are effective for serious infections or resistant organisms and are often used in the intensive care unit or for nosocomial intra-abdominal infection. These classes of beta-lactams comprise a range of antimicrobials that can be targeted effectively as single agents to both prevention and treatment of intra-abdominal infection.

Topics: Abdomen; Abdominal Abscess; Ampicillin; Anti-Bacterial Agents; Bacterial Infections; beta-Lactamase Inhibitors; Carbapenems; Cephalosporins; Clavulanic Acids; Drug Resistance, Bacterial; Drug Therapy, Combination; Enzyme Inhibitors; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sulbactam; Surgical Wound Infection; Ticarcillin

Topics: Bacterial Infections; Drug Therapy, Combination; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests; Molecular Structure; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

To discuss the antimicrobial activity, pharmacokinetics, clinical efficacy, and adverse effect profile of piperacillin/tazobactam, a new beta-lactan/beta-lactamase inhibitor combination.. Literature was identified by MEDLINE search of the medical literature, review of selected references, and data provided by the manufacturer.. In vitro susceptibility data were surveyed from studies following the methods of the National Committee for Clinical Laboratory Standards. Data evaluating clinical efficacy were selected from all published trials and abstracts. Additional information concerning safety, chemistry, and pharmacokinetics was reviewed.. The antimicrobial activity of piperacillin is enhanced by addition of tazobactam against gram-positive, gram-negative, and anaerobic bacteria. Tazobactam is active against a broad spectrum of plasmid and chromosomally mediated enzymes and has minimal ability to induce class I chromosomally mediated beta-lactamase enzymes. Piperacillin/tazobactam's expanded activity appears encouraging in the treatment of mixed aerobic and anaerobic infections. Direct comparisons of ticarcillin/clavulanate and piperacillin/tazobactam for the treatment of lower respiratory tract infections showed piperacillin/tazobactam to be clinically superior, and in the treatment of skin and soft tissue infections the 2 agents were comparable. For the treatment of intraabdominal infections, piperacillin/tazobactam was at least as effective as imipenem/cilastatin and clindamycin plus gentamicin.. The combination of tazobactam with piperacillin results in an antimicrobial agent with enhanced activity against most beta-lactamase-producing organisms. Preliminary data indicate that piperacillin/tazobactam has proven clinical efficacy in the treatment of a variety of infections, especially polymicrobic infections.

Topics: Bacterial Infections; beta-Lactamase Inhibitors; Child; Child, Preschool; Clinical Trials as Topic; Drug Therapy, Combination; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Infant; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Tazobactam

Bloodstream infections (BSIs) adversely affect clinical outcome in children with cancer. Over 1 decade, this retrospective cohort study describes pathogen distribution in BSIs and antimicrobial susceptibility against empirical antibiotics frequently prescribed in children with cancer. The antibiotic efficacy was evaluated through the determination of minimal inhibitory concentrations for piperacillin-tazobactam and meropenem and by disk diffusion for remaining antibiotics. From 2004 to 2013, 398 BSIs occurred in 196 children with cancer (median age: 5.4 y), resulting in 457 bacteria. Overall, 266 (58.2%) were Gram-positive, and 191 (41.8%) were Gram-negative with a significant Gram-positive increase over time (P=0.032). Coagulase-negative staphylococci (74, 16.2%), viridans group streptococci (67, 14.7%), Escherichia coli (52, 11.4%), and Staphylococcus aureus (39, 8.5%) were the most common pathogens. Susceptibility to piperacillin-tazobactam (95.9%, P=0.419) and meropenem (98.9%, P=0.752) was stable over time, and resistance was observed among viridans group streptococci against piperacillin-tazobactam (18%) and meropenem (7%) and among Enterobacterales against piperacillin-tazobactam (3%). Vancomycin showed 98% Gram-positive activity, gentamicin 82% Gram-negative activity and ampicillin, cefotaxime, and cefuroxime were active in 50%, 72%, and 69% of pathogens, respectively, and BSI-related mortality was 0%. In conclusion, over 1 decade, we report an increase in Gram-positive BSIs, and stable, low-resistance rates against currently recommended empirical antibiotics, piperacillin-tazobactam and meropenem.

Topics: Adolescent; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Meropenem; Microbial Sensitivity Tests; Neoplasms; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Sepsis

To evaluate clinically the efficacy and safety in northern India of cefepime monotherapy versus piperacillin-tazobactam in patients of paediatric age group with febrile neutropenia.. Children aged ≤18 years admitted febrile with chemotherapy-induced neutropenia were randomised into two groups comprising 20 cases in each group viz. CEF (receiving cefepime only) and PIP-TAZO (receiving piperacillin-tazobactam). Based on clinical and laboratory tests, patients were classified into: microbiologically documented infections (MDI); clinically documented infections (CDI); and unexplained fever (UF). They were assessed for clinical signs and symptoms as well as laboratory parameters at the time of enrolment and subsequently on days 3 and 7.. Incidence of MDI, CDI and UF were 22.5%, 47.5% and 30%, respectively. The mean duration of neutropenia (in days) was 5.45 ± 2.1 in the PIP-TAZO group and 5.5 ± 1.5 in the CEF group (P = 0.305). The success rate defined as clearing infection effectively and improvement of neutropenia was comparable (P = 0.705). There was a mortality rate of 20% in the PIP-TAZO group as compared to 10% in the CEF group.. We conclude that cefepime monotherapy and piperacillin-tazobactam are equally efficacious and safe in treating patients with febrile neutropenia. Empirical monotherapy with cefepime would prevent an unnecessary extra economic burden as well as avoiding the serious adverse or toxic effects of multi-drug regimes, especially in low- and middle-income countries.

Topics: Adolescent; Anti-Bacterial Agents; Bacterial Infections; Cefepime; Cephalosporins; Child; Child, Preschool; Drug Therapy, Combination; Febrile Neutropenia; Female; Fever; Humans; India; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Tertiary Care Centers; Treatment Outcome

Few randomized controlled studies have compared antibiotic regimens against diabetic foot infections (DFIs) in Chinese patients. We evaluated the efficacy and safety of ertapenem versus piperacillin/tazobactam for the treatment of DFIs in Chinese patients.. Patients with moderate to severe DFIs requiring parenteral antibiotics were randomized in a 1 : 1 ratio to receive ertapenem (1.0 g once daily) or piperacillin/tazobactam (4.5 g every 8 h) by 30 min intravenous (iv) infusions for ≥5 days. The primary outcome was favourable clinical response at discontinuation of iv therapy (DCIV). An evaluable-patient population was identified for primary analysis of non-inferiority at -15%. Safety was assessed. ClinicalTrials.gov: NCT01370616.. Of 565 patients randomized, 443 patients (ertapenem = 219 and piperacillin/tazobactam = 224) were clinically evaluable for primary analysis. In the clinically evaluable population, the proportions of patients with favourable clinical response at DCIV were 93.6% (205/219) and 97.3% (218/224) in the ertapenem and piperacillin/tazobactam groups, respectively (difference: -3.8%, 95% CI: -8.3%, 0.0%). Ertapenem had a significantly lower favourable clinical response rate (91.5% versus 97.2%, 95% CI for difference: -12.1%, -0.3%) at DCIV in severe DFI patients. In the modified ITT population, 88.8% (237/267) and 90.6% (241/266) of patients in the ertapenem and piperacillin/tazobactam groups, respectively, had favourable clinical responses at DCIV (difference: -1.9%, 95% CI: -7.3%, 3.3%). Microbiological eradications of causative pathogens and adverse events were similar between treatment groups.. Treatment with ertapenem was non-inferior to piperacillin/tazobactam in Chinese patients with DFIs. Ertapenem treatment resulted in a markedly lower rate of clinical resolution in severe DFIs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; beta-Lactamase Inhibitors; beta-Lactams; China; Diabetic Foot; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Ertapenem; Female; Humans; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Treatment Outcome; Young Adult

To evaluate the efficacy and safety of piperacillin/tazobactam (PIPC/TAZ) or cefepime (CFPM) monotherapy for febrile neutropenia (FN) in children, a total of 53 patients with 213 febrile episodes were randomly treated with either PIPC/TAZ 337.5 mg/kg/day, or CFPM 100 mg/kg/day. No significant differences were observed in the success rates of the PIPC/TAZ and CFPM treatments (62.1% vs. 59.1%, P = 0.650). Furthermore, no differences were noted in the rates of new infection and mortality, and no serious adverse effects occurred in either of groups. Both PIPC/TAZ and CFPM were effective and safe as an empirical therapy for FN in children. Pediatr Blood Cancer 2015;62:356-358. © 2014 Wiley Periodicals, Inc.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Bacterial Infections; Cefepime; Cephalosporins; Child; Child, Preschool; Febrile Neutropenia; Female; Hematologic Neoplasms; Humans; Infant; Infant, Newborn; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Young Adult

Determination of risk of severe bacterial infection complication in children with cancer is important to diminish the cost of hospitalization and therapy. In this study, children with cancer (leukemia excluded) were evaluated for risk of severe infection complication, success of therapy and the relation between clinical and inflammatory parameters during neutropenic fever attacks. Children who fulfilled the criteria of neutropenic fever with cancer were enrolled in the study. During admission, together with clinical and laboratory parameters; interleukin-6, interleukin-8, soluble tumor necrosis factor receptor II, and soluble interleukin 2 reseptor ve procalcitonin levels were detected. Empirical therapy was started with piperacillin/tazobactam and relation between the inflammatory cytokine levels and therapy response parameters were evaluated. The study population included 31 children and 50 neutropenic attacks were studied. In 48% of the attacks, absolute neutrophile count was >100/mm(3) and infectious agents were shown microbiologically in 12% of the attacks. In the study group with piperacillin/tazobactam monotherapy, the success rate without modification was 58%. In the therapy modified group mean duration of fever, antibiotherapy and hospitalization were significantly longer than the group without modification. Inflammatory cytokines' levels during admission (interleukin-6, interleukin-8, soluble tumor necrosis factor reseptor II) were higher in patients with fever >3 days and in multiple regression analysis, it has been shown that they have a determinative role on fever control time. Other cytokines did not show any significant relationship with risk of severe bacterial infection complication and success of therapy.

Topics: Adolescent; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Cytokines; Female; Fever; Humans; Infant; Inflammation Mediators; Male; Neoplasms; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Predictive Value of Tests; Risk Factors

Neonates at risk for early-onset sepsis are started on antibiotics empirically. Antibiotic resistance to conventionally used antibiotics is increasingly being reported. Antenatal maternal antibiotic exposure in this setting contributes to low yield on blood culture drawn at birth, limiting the planning of antibiotics based on culture reports. A head-to-head comparison for selecting the appropriate antibiotic is one strategy.. To compare monotherapy with amikacin against piperacillin-tazobactum as an empirical therapy in neonates at risk for early-onset sepsis.. Randomized open-label controlled trial with stratification and block randomization.. Tertiary care neonatal unit in India. All consecutive inborn neonates delivered between 01 May 2009 and 30 April 2011 who were ≥28 week gestation and/or ≥1000 g birth weight with risk factors for early-onset sepsis.. Randomized to receive either amikacin or piperacillin-tazobactum, after stratifying as asymptomatic or symptomatic within 1 h of birth.. Incidence of treatment failure to the allocated antibiotic defined as blood culture isolate reported resistant to the allocated antibiotic or progression of the illness, necessitating a change of antibiotic.. Of 204 eligible cases, 187 were enrolled. Seventeen babies were excluded. A total of 128 neonates were stratified as asymptomatic and 59 as symptomatic. In all, 64 of the asymptomatic cases received amikacin and 64 received piperacillin-tazobactum, while 29 symptomatic babies received amikacin and 30 received piperacillin-tazobactum. Five babies had blood culture-positive sepsis, and 28 babies had strong suspicion of sepsis. There was no difference in the treatment failure in the amikacin group (3 of 93; 3.2%) compared with piperacillin-tazobactum group (2 of 94; 2.1%) (p > 0.01) and no difference in the incidence of second infection, fungal sepsis and all-cause mortality at day 7 and 28 between the two study groups (p > 0.01).. Monotherapy with amikacin as an empirical antibiotic did not result in a higher incidence of treatment failure in neonates at risk for early-onset sepsis as compared with piperacillin-tazobactum. Both antibiotics were effective in management of babies with early-onset sepsis.

Topics: Amikacin; Anti-Bacterial Agents; Bacterial Infections; Drug Therapy, Combination; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; India; Infant, Newborn; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Risk Factors; Sepsis; Treatment Outcome

The aim of this study was to evaluate the efficacy and safety of piperacillin/tazobactam (PIP/TAZO) and cefozopran (CZOP) monotherapy in pediatric cancer patients with febrile neutropenia (FN).. A total of 119 febrile episodes in 49 neutropenic pediatric cancer patients (20 females and 29 males) with a median age of 6.8 years (range, 0.3-18.4 years) received randomized treatment either with PIP/TAZO 125 mg/kg every 8 hr or CZOP 25 mg/kg every 6 hr. Clinical response was determined at completion of therapy. Durations of fever and neutropenia, the need for modification of the therapy, and mortality rates were compared between the two groups.. The frequency of success without modification of treatment was not significantly different between PIP/TAZO (59.6%) and CZOP (53.2%). Durations of fever and antibiotic therapy did not differ between the treatment groups, and no major side effects were observed in either group.. PIP/TAZO and CZOP monotherapy were both effective and safe for the initial empirical treatment of pediatric cancer patients with FN.

Topics: Adolescent; Anti-Bacterial Agents; Bacterial Infections; Cefozopran; Cephalosporins; Child; Child, Preschool; Female; Fever; Humans; Male; Neoplasms; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

In view of the recent trend toward monotherapy in the treatment of febrile neutropenia, we evaluated the clinical efficacy and safety of imipenem-cilastatin versus piperacillin-tazobactam as an empiric therapy for febrile neutropenia in children with malignant diseases.. Febrile neutropenic patients received either imipenem-cilastatin or piperacillin-tazobactam randomly. Improvement without any changes in the initial antibiotic treatment was defined as "success" and improvement with modification of the initial treatment and death was defined as "failure".. Over 12 months, 99 febrile neutropenic episodes were treated with monotherapy in 63 patients with a median age of 5 years. At admission, median absolute neutrophil count was 50/mm(3) and in 67% of episodes, neutrophil count was under 100/mm(3). Median duration of neutropenia was 5 days. In 22% of episodes, neutropenia persisted for more than 10 days. Piperacillin-tazobactam was used in 52 episodes and imipenem-cilastatin was used in 47 episodes. There was no difference between groups in terms of age, sex, primary diseases, neutrophil count or duration of neutropenia. In the whole group, the success rate was 67% and the failure rate was 33%, whereas in the piperacillin-tazobactam group, the rates were 71% and 29%; and in the imipenem-cilastatin group they were 62% and 38%, respectively (P > 0.05). There were no deaths. No major adverse effects were seen in either group.. Although failure was slightly higher in the imipenem-cilastatin group, this was statistically insignificant. Both of these antibiotics can be used safely for initial empirical monotherapy of febrile neutropenia.

Topics: Adolescent; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Fever; Humans; Imipenem; Male; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies

In this prospective, randomized, open-label clinical trial, we compared the efficacy and safety of two antibiotic regimens for severe diabetic foot infections (DFI). Sixty-two in-patients with DFI received either piperacillin/tazobactam (Pip-Tazo, n = 30) (4.5 g intravenously every 8h) or imipenem/cilastatin (IMP, n = 32) (0.5 g intravenously every 6h). The mean duration of treatment was 21 days for Pip-Tazo and 24 days for IMP. Twenty-two (73.3%) patients in the Pip-Tazo group and 26 (81.2%) patients in the IMP group had DFI associated with osteomyelitis. Successful clinical response was seen in 14 (46.7%) patients in the Pip-Tazo group and in nine (28.1%) patients in the IMP group [relative risk (RR) 1.6 (95% CI 0.84-3.25), p 0.130]. Two patients in the IMP group and none in the PIP-Tazo group relapsed [RR 2 (0.94-4.24), p 0.058]. Eighty-nine microorganisms were isolated: 38 (43%) Gram-positive and 51(57%) Gram-negative. Among patients with positive culture, 47 (96%) had complete and two (4%) had partial microbiological response. Microbiological response rates were similar in both groups (p 1.000). Amputation was performed in 18 (60%) and 22 (69%) patients in the Pip-Tazo and IMP groups (p 0.739) respectively. Side effects were more common in the Pip-Tazo group (30% vs. 9.4%), but they were generally mild and reversible. In conclusion, although the sample size was small and the results did not reach statistical significance, Pip-Tazo produced a better clinical response rate than IMP in the treatment of severe DFI. There was no significant difference between the treatment groups with respect to microbiological response, relapse and amputation rates.

Topics: Adult; Aged; Aged, 80 and over; Amputation, Surgical; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Diabetic Foot; Drug Combinations; Female; Hospitals, University; Humans; Imipenem; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Recurrence; Time Factors; Treatment Outcome

Empirical beta-lactam monotherapy has become the standard therapy in febrile neutropenia. The aim of this study was to compare the efficacy and safety of piperacillin-tazobactam versus carbapenem therapy with or without amikacin in adult patients with febrile neutropenia.. In this prospective, open, single-center study, 127 episodes were randomized to receive either piperacillin-tazobactam (4 x 4.5 g IV/day) or carbapenem [meropenem (3 x 1 g IV/day) or imipenem (4 x 500 mg IV/day)] with or without amikacin (1 g IV/day). Doses were adjusted according to renal function. Clinical response was determined during and at completion of therapy.. One hundred and twenty episodes were assessable for efficacy (59 piperacillin-tazobactam, 61 carbapenem). Mean duration of treatment was 14.8 +/- 9.6 days in the piperacillin-tazobactam group and 14.7 +/- 8.8 days in the carbapenem group (P > 0.05). Mean days of fever resolution were 5.97 and 4.48 days for piperacillin-tazobactam and carbapenem groups, respectively (P > 0.05). Similar rates of success without modification were found in the piperacillin-tazobactam (87.9%) and in the carbapenem groups (75.4%; P > 0.05). Fungal infection occurrence rates were 30.5 and 18% in piperacillin-tazobactam and carbapenem groups, respectively (P = 0.05). Antibiotic modification rates were 30.5 and 13.1% (P = 0.02) and the addition of glycopeptides to empirical antibiotic regimens rates were 15.3 and 44.3% for piperacillin-tazobactam and carbapenem groups, respectively (P = 0.001). The rude mortality rates were 14% (6/43) and 29.3% (12/41) in piperacillin-tazobactam and carbapenem groups, respectively (P = 0.08).. The effect of empirical regimen of piperacillin-tazobactam regimen is equivalent to carbapenem in adult febrile neutropenic patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amikacin; Anti-Bacterial Agents; Antineoplastic Agents; Bacterial Infections; Carbapenems; Drug Eruptions; Drug Therapy, Combination; Female; Fever; Humans; Male; Middle Aged; Multivariate Analysis; Neoplasms; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Survival Rate; Young Adult

We evaluated piperacillin-tazobactam in association with amikacin in the initial empirical therapy of febrile neutropenic children.. An open-labelled, non-randomised, prospective trial to assess the efficacy and safety of this association was conducted from June 1, 2001 to December 31, 2002. Children and adolescents were treated for a haematological malignancy or a primary, refractory or relapsed solid tumour, and presented with febrile neutropenia. Patients received intravenous piperacillin-tazobactam (90 mg/kg/dose every eight hours) plus a single daily dose of amikacin at 15 mg/kg/day, maximum 250 mg. If fever persisted, second-line therapy with carbapenem was administered. Teicoplanin was added for gram-positive isolates or for unremitting fever after 48 hours, if clinically indicated. Amphotericin B was added at 96 hours, if fever and neutropenia persisted.. 155 episodes of fever and neutropenia in 76 patients were evaluable. 40 (25.8 percent) episodes were a microbiologically-documented infection, 30 (19.4 percent) were clinically-documented, and 85 (54.8 percent) were unexplained fever. 77 (49.7 percent) episodes responded to piperacillin-tazobactam plus amikacin without a need for treatment modification. A higher success rate (63.5 percent) was observed in episodes with unexplained fever. The predominant pathogens isolated in our study were gram-negative organisms (70.7 percent). A mild gastrointestinal intolerance occurred in 35 out of 155 (22.6 percent) episodes.. This study suggests that piperacillin-tazobactam plus amikacin presents a satisfactory efficacy and a good tolerance as initial empirical therapy for febrile neutropenic children.

Topics: Adolescent; Adult; Amikacin; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Drug Therapy, Combination; Female; Humans; Infant; Male; Neoplasms; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

A prospective, randomized clinical trial was conducted to compare the efficacy of piperacillin/tazobactam and amikacin combination with carbapenem monotherapy for the empirical treatment of febrile neutropenic episodes of children with acute lymphoblastic leukemia or acute myeloblastic leukemia. Patients aged 2-16 years with hematological malignancies who had febrile neutropenia were randomly assigned to receive piperacillin/tazobactam (80 mg/kg piperacillin/10 mg/kg tazobactam, q6h) combined with amikacin (PTA) (7.5 mg/kg, q12h) or meropenem or imipenem (20 mg/kg, q8h) (C). Response to antimicrobial therapy, evaluated for etiological agents, was measured. Duration of fever, neutropenia, and hospitalization, mortality, and the need for additional antibiotics or antifungal drugs were compared for the treatment success between the two groups. Out of 87 febrile neutropenic episodes that were evaluable for comparison, 46 patients received PTA and 41 patients were treated with carbapenems (imipenem or meropenem). Overall, the microbiologically documented infection rate was 21.9%, with Staphylococcus epidermidis as the most common cause of bacteremia. The rate of treatment modification was 56.5% in the PTA group and 53.6% in the carbapenem group with no statistical difference (p > .05). There was no infection-related mortality during the study period. There was no difference between the two regimens for durations of fever, neutropenia, and hospitalization (p > .05 for all categories). PTA was as effective as carbapenem monotherapy as an initial empirical regimen in febrile neutropenic episodes of pediatric hematological malignancies.

Topics: Adolescent; Amikacin; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Carbapenems; Child; Child, Preschool; Drug Therapy, Combination; Enzyme Inhibitors; Female; Humans; Leukemia, Myeloid, Acute; Male; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Complicated intra-abdominal infections are a common problem in surgical practice. This study compared the effectiveness of ertapenem (1 g qd) and piperacillin/tazobactam (3.375 g q6h) in the treatment of these infections.. This was a multicenter, double-blinded, randomized study conducted in patients with complicated intra-abdominal infections. Of the 535 patients screened, 500 were stratified on the basis of disease severity (Acute Physiology and Chronic Health Evaluation [APACHE] II score < or =10 or >10), then randomized (1:1) to 4-14 days of treatment with one of the regimens and six weeks of followup. Nearly all patients (N = 494) were treated. The primary endpoint was the proportion of microbiologically evaluable patients with a favorable clinical response (cure) at two weeks. Non-inferiority of ertapenem was based on a difference in response rate of <15 percentage points compared with piperacillin/tazobactam (lower bound of the 95% CI > -15).. Of the 494 treated patients, 231 were microbiologically evaluable, with 123 and 108 patients in the ertapenem and piperacillin/tazobactam groups, respectively. Statistically similar cure rates were observed in the ertapenem (82.1%) and piperacillin/tazobactam (81.7%) groups (difference 0.3 [95% CI: -9.6, 10.5]). The pathogens isolated most frequently were Escherichia coli, Bacteroides fragilis, and Bacteroides thetaiotamicron, typical isolates associated with intra-abdominal infections. There were no statistical differences between the groups in serious drug-related clinical adverse events, drug-related clinical adverse experiences leading to study discontinuation, or mortality.. Ertapenem was non-inferior to piperacillin/tazobactam in the cure of intra-abdominal infections caused by susceptible pathogens. Both study drugs generally were well tolerated.

Topics: Abdominal Abscess; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; APACHE; Bacterial Infections; Bacteroides; beta-Lactams; Double-Blind Method; Ertapenem; Escherichia coli; Female; Humans; Male; Middle Aged; Penicillanic Acid; Peritonitis; Piperacillin; Piperacillin, Tazobactam Drug Combination

Complicated intra-abdominal infections usually mandate prompt surgical intervention supplemented by appropriate antimicrobial therapy. The aim of this study was to demonstrate that ertapenem was not inferior to piperacillin-tazobactam for the treatment of community-acquired intra-abdominal infections. A randomized open-label active-comparator clinical trial was conducted at 48 medical centers on four continents from December 2001 to February 2003. Adult patients with intra-abdominal infections requiring surgery were randomized to receive either ertapenem 1 g daily or piperacillin/tazobactam 13.5 g daily in 3-4 divided doses. The primary analysis of efficacy was the clinical response rate in clinically and microbiologically evaluable patients at the test-of-cure assessment 2 weeks after completion of therapy. All treated patients were included in the safety analysis. Patient demographics, disease characteristics, and treatment duration in both treatment groups were generally similar. The most commonly isolated pathogens at baseline were E coli (greater than 50% of cases in each group) and B fragilis ( approximately 9%). Favorable clinical response rates were 107/119 (90%) for ertapenem recipients and 107/114 (94%) for piperacillin/tazobactam recipients. The frequencies of drug-related adverse events, most commonly diarrhea and elevated serum alanine aminotransferase levels, were similar in both treatment groups. Six of 180 ertapenem recipients (3%) and two of 190 piperacillin/tazobactam recipients (1%) had serious drug-related adverse experiences. In this study, ertapenem and piperacillin/tazobactam were comparably safe and effective treatments for adult patients with complicated intra-abdominal infections.

Topics: Abdomen; Abscess; Adolescent; Adult; Aged; Aged, 80 and over; Alanine Transaminase; Anti-Bacterial Agents; Bacterial Infections; Bacteroides fragilis; Bacteroides Infections; beta-Lactams; Diarrhea; Ertapenem; Escherichia coli Infections; Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Penicillanic Acid; Peritonitis; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Treatment Outcome

To compare the safety and efficacy of sequential intravenous (IV) to oral (PO) moxifloxacin treatment against a standard antimicrobial regimen of IV piperacillin-tazobactam followed by PO amoxicillin-clavulanate for the treatment of adults with complicated intra-abdominal infection (cIAI).. cIAIs are commonly due to mixed aerobic and anaerobic bacteria and require both source control and broad-spectrum antibiotic therapy.. A prospective, double-blind, randomized, phase III comparative trial. Patients with cIAI were stratified by disease severity (APACHE II score) and randomized to either IV/PO moxifloxacin (400 mg q24 hours) or comparator (IV piperacillin-tazobactam [3.0/0.375 g q6 hours] +/- PO amoxicillin-clavulanate [800 mg/114 mg q12 hours]), each for 5 to 14 days. The primary efficacy variable was clinical cure rate at the test-of-cure visit (days 25-50). Bacteriologic outcomes were also determined.. : Of 656 intent-to-treat patients, 379 (58%) were valid to assess efficacy (183 moxifloxacin, 196 comparator). Demographic and baseline medical characteristics were similar between the 2 groups. Clinical cure rates at test-of-cure were 80% (146 of 183) for moxifloxacin versus 78% (153 of 196) for comparator (95% confidence interval, -7.4%, 9.3%). The clinical cure rate at test-of-cure for hospital-acquired cIAI was higher with moxifloxacin (82%, 22 of 27) versus comparator (55%, 17 of 31; P = 0.05); rates were similar for community-acquired infections (80% [124 of 156] versus 82% [136 of 165], respectively). Bacterial eradication rates were 78% (117 of 150) with moxifloxacin versus 77% (126 of 163) in the comparator group (95% confidence interval, -9.9%, 8.7%).. Once daily IV/PO moxifloxacin monotherapy was as least as effective as standard IV piperacillin-tazobactam/PO amoxicillin-clavulanate dosed multiple times daily for the treatment of cIAIs.

Topics: Abdominal Abscess; Administration, Oral; Adult; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Appendicitis; Aza Compounds; Bacterial Infections; Cross Infection; Double-Blind Method; Female; Fluoroquinolones; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Injections, Intravenous; Intestinal Perforation; Male; Middle Aged; Moxifloxacin; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Quinolines; Safety; Stomach Rupture; Treatment Outcome

Soft tissue and bone infections of the lower limb continue to be a frequent and serious complication in patients with diabetes mellitus. The best choice of antimicrobial for the empiric treatment of moderate to severe diabetic foot infections has not been established clearly.. We conducted a prospective, randomized, open-label, multicenter trial comparing piperacillin/tazobactam (P/T) (4 g/0.5 g q8h) and ampicillin/sulbactam (A/S) (2 g/1 g q6h) as a parenteral treatment for 314 adult patients with moderate-to-severe infected diabetic foot ulcers. Patients with polymicrobial infections involving methicillin-resistant Staphylococcus aureus also received vancomycin 1 g q12h.. Clinical efficacy rates (cure or improvement) were statistically equivalent overall (81% for P/T vs. 83.1% for A/S), and median duration of treatment was similar in the clinically evaluable populations (nine days for P/T, 10 days for A/S). Drug-related adverse events for both study drugs were comparable in frequency and type.. Although both study drugs provide safe and effective empiric treatment for moderate-to-severe infected diabetic foot ulcers, piperacillin/tazobactam has the advantage of covering Pseudomonas aeruginosa (bacteriologic success rate of 85.7%), the most commonly isolated gram-negative pathogen in this study.

Topics: Ampicillin; Anti-Bacterial Agents; Bacterial Infections; Diabetic Foot; Female; Humans; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Sulbactam; Time Factors; Vancomycin; Wound Infection

The safety and efficacy of early bacterial prophylaxis with piperacillin-tazobactam were prospectively evaluated in 51 autologous peripheral blood stem cell transplantation (PBSCT) recipients. The results were compared with those obtained in 51 control patients receiving oral fluoroquinolones in a retrospective matched-pair control study. Overall, 76% of the study group and 98% of the control group developed at least one febrile episode during neutropenia (P=0.002). Time from neutropenia to the first febrile episode (FFE) was significantly longer in the study group than in the control group (P=0.04). Once a febrile episode appeared, the duration of fever was significantly longer in cases than in controls (median of 5 and 2 days respectively, P<0.001), and led to a more frequent use of empirical amphotericin B (AmB), not statistically significant (P=0.13). However, the total time of antibiotic administration was significantly greater in the control than in the study group (P=0.05). The duration of AmB treatment shows a trend toward a longer duration in the control than in study group (P=0.2). Overall, 86% of the Gram-positive bacteremia and 85% of the Gram-negative bacteria were susceptible to the tested antibiotics. Our study suggests that a subgroup of patients could benefit from prophylaxis with piperacillin-tazobactam without increasing toxicity or bacterial resistance.

Topics: Adolescent; Adult; Aged; Amphotericin B; Bacteremia; Bacterial Infections; Female; Fever; Fluoroquinolones; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Male; Matched-Pair Analysis; Middle Aged; Neutropenia; Penicillanic Acid; Peripheral Blood Stem Cell Transplantation; Piperacillin; Piperacillin, Tazobactam Drug Combination; Premedication; Transplantation, Autologous

A post-hoc analysis of data from a trial of complicated intra-abdominal infection was performed to compare the demographic and disease characteristics of patients with complicated appendicitis to those whose primary infection involved other intra-abdominal sites, assess the impact of site of primary infection on outcome, and compare the efficacy and safety of ertapenem 1 g daily with piperacillin-tazobactam 3.375 g every 6 h for treatment of complicated appendicitis. Compared with patients who had primary infection of the colon or another site in the abdomen, patients with complicated appendicitis were younger, had less severe disease (based on lower APACHE II score and lower proportion with generalized peritonitis), and were less likely to be managed by percutaneous drainage of an abscess or to have a postoperative infection. Patients with complicated appendicitis were more likely to have a favorable outcome than were patients with infection of the colon (OR, 3.02; 95% CI, [1.54-5.901; P = .001). At the test-of-cure assessment, 109/123 (88.6%) microbiologically evaluable patients with complicated appendicitis who received ertapenem and 102/113 (90.3%) who received piperacillin-tazobactam had a favorable combined clinical and microbiologic outcome. The frequency and severity of drug-related adverse events were similar in the two treatment groups.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anti-Bacterial Agents; Appendicitis; Bacterial Infections; beta-Lactams; Colonic Diseases; Demography; Double-Blind Method; Ertapenem; Female; Humans; Lactams; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Risk Factors; Severity of Illness Index

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

An optimum antimicrobial regimen for bacterial infection after orthotopic liver transplantation has not been identified. In this prospective 4 year study of patients undergoing liver transplantation, patients were randomized to receive either piperacillin-tazobactam (112 patient episodes) or ciprofloxacin plus amoxicillin (105 patient episodes) for empirical treatment of infective episodes in the first 3 months after transplant. Metronidazole was added to the ciprofloxacin-amoxicillin regimen where anaerobic infection was suspected. Patient groups were comparable with respect to clinical, biochemical and haematological parameters. At the 72 h primary efficacy end-point, the overall response rate for the intention-to-treat group was 74/112 (66.1%) for piperacillin-tazobactam and 63/105 (60.0%) for ciprofloxacin plus amoxicillin (P=0.399); the corresponding figures for the per-protocol (PP) group were 73/82 (89.0%) (piperacillin-tazobactam) and 61/80 (76.3%) (ciprofloxacin plus amoxicillin) (P=0.038). At the end-of-study assessment, 58.9% of episodes in the piperacillin-tazobactam group had a successful clinical outcome, compared with 50.5% in the ciprofloxacin plus amoxicillin group (P=0.222); the corresponding figures for the PP group were 83.5% (piperacillin-tazobactam) and 68.8% (ciprofloxacin plus amoxicillin) (P=0.038). Staphylococci and aerobic Gram-negative bacilli were the predominant pathogens in both groups. Bacteria resistant to the study drugs were encountered, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium and multiply-resistant Klebsiella spp. Empirical monotherapy with piperacillin-tazobactam is an effective treatment for infective episodes in liver transplant patients.

Topics: Adolescent; Adult; Aged; Amoxicillin; Anti-Bacterial Agents; Bacterial Infections; Ciprofloxacin; Double-Blind Method; Drug Therapy, Combination; Enterobacteriaceae; Female; Fever; Humans; Liver Transplantation; Male; Metronidazole; Middle Aged; Penicillanic Acid; Penicillins; Piperacillin; Piperacillin, Tazobactam Drug Combination; Postoperative Complications; Prospective Studies; 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

To compare continuous versus intermittent administration of piperacillin-tazobactam with regard to clinical, microbiologic, and economic outcomes.. Prospective, open-label controlled study. Community teaching hospital.. Ninety-eight hospitalized patients prescribed piperacillin-tazobactam.. Substitutions were implemented so that 47 patients initially prescribed intermittent infusion of piperacillin-tazobactam were switched to continuous infusion of this drug combination. Dosages varied in accordance with the type of infection and each patient's renal function. Fifty-one other patients with similar demographics and types of infection received intermittent infusion with piperacillin-tazobactam.. Clinical success rates were 94% for the continuous-infusion group and 82% for the intermittent-infusion group (p=0.081). Microbiologic success rates were 89% for the continuous-infusion group and 73% for the intermittent-infusion group (p=0.092). Days to normalization of fever were significantly lower (p=0.012) in the continuous-infusion group (1.2 +/- 0.8 days) than in the intermittent-infusion group (2.4 +/- 1.5 days). Level 1 and level 2 costs/patient were both reduced by continuous infusion, although the difference was statistically significant only for level 2 costs ($399.38 +/- 407.22 for continuous infusion vs $523.49 +/- 526.85 for intermittent infusion, p=0.028).. Continuous infusion of piperacillin-tazobactam provided clinical and microbiologic outcomes equivalent to those for intermittent infusion. Compared with intermittent infusion, continuous infusion significantly shortened the time to temperature normalization, while also offering a significant reduction in level 2 expenditures.

Topics: Aged; Aged, 80 and over; Bacterial Infections; Chi-Square Distribution; Drug Therapy, Combination; Female; Hospitals, Community; Hospitals, Teaching; Humans; Infusions, Intravenous; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Statistics, Nonparametric

In a prospective, multicenter, double-blind, randomized clinical trial, we compared the efficacy of piperacillin-tazobactam (4.5 g 3 times daily intravenously) plus placebo versus piperacillin-tazobactam plus amikacin (7.5 mg/kg twice daily intravenously) for the treatment of 760 febrile, adult patients with cancer with chemotherapy-induced profound (<500 neutrophils/mm3) and prolonged (>10 days) neutropenia. A total of 733 patients were assessable for efficacy of the drug regimens, and an overall successful outcome was reported in 49% (179 of 364) of the patients who received monotherapy, compared with 53% (196 of 369) of patients who received combination therapy (P=.2). Response rates were similar with both regimens, as were incidences of bacteremia and clinically documented and possible infections. In our epidemiological setting, the initial empiric combination therapy was not associated with improved outcomes when compared with initial monotherapy.

Topics: Adolescent; Adult; Aged; Amikacin; Anti-Bacterial Agents; Bacterial Infections; Double-Blind Method; Drug Therapy, Combination; Female; Fever; Humans; Male; Middle Aged; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Treatment Outcome

A predictive parameter of beta-lactam therapeutic efficacy is the time (T > MIC) while antibiotic serum concentrations are above the MIC of suspected bacteriological agents. This led us to carry out a randomised open study to compare the usually used intermittent administration of Tazocin (three injections of 4 g/0.5 g a day) and continuous perfusion of 12 g/1.5 g a day by calculating these T > MIC. Patients from digestive reanimation department were randomised within two arms: continuous or intermittent administration. Sixteen takings of blood were executed over a forty-hour period. After liquid/liquid extraction, piperacillin and tazobactam serum concentrations were determined by HPLC with a reversed phase column (C18) and a UV spectrophotometry detection. Then, from the time-concentration curves we have evaluated the T > MIC for an enterobacteria (MIC = 8 micrograms/mL) and for Pseudomonas (MIC = 16 micrograms/mL). Concerning intermittent administration T > MIC were 74% (c > MICenterobacteria) and 62% (c > MICPseudomonas). These percentages in the continuous arm were 100% (c > MICenterobacteria) and 99% (c > MICPseudomonas). Tazobactam concentrations were low and even undetectable between each injection in the intermittent administration arm. This was not found within the continuous administration arm. In conclusion, for the intermittent administration, we observed some long periods occurring before each injection while antibiotic concentrations were under the MIC of most bacteria. During these same periods tazobactam concentrations were under the efficacy threshold. These periods were not observed within the continuous administration arm.

Topics: Adolescent; Adult; Aged; Area Under Curve; Bacteria, Anaerobic; Bacterial Infections; Drug Administration Schedule; Drug Therapy, Combination; Enterobacteriaceae Infections; Female; Gram-Positive Bacterial Infections; Humans; Infusions, Intravenous; Male; Microbial Sensitivity Tests; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

To compare the safety and efficacy of intravenous (IV) ciprofloxacin plus IV metronidazole (CIP+MET) with that of IV piperacillin/tazobactam (PIP/TAZO) in adults with complicated intraabdominal infections, and to compare the efficacy of sequential IV-to-oral CIP+MET therapy with that of the IV CIP-only regimen.. Treatment of intraabdominal infections remains a challenge, mainly because of their polymicrobial etiology and attendant death and complications. Antimicrobial regimens using sequential IV-to-oral therapy may reduce the length of hospital stay.. In this multicenter, randomized, double-blind trial involving 459 patients, clinically improved IV-treated patients were switched to oral therapy after 48 hours. Overall clinical response was the primary efficacy measurement.. A total of 282 patients (151 CIP+MET, 131 PIP/TAZO) were valid for efficacy. Of these patients, 64% CIP+MET and 57% PIP/TAZO patients were considered candidates for oral therapy. Patients had a mean APACHE II score of 9.6. The most common diagnoses were appendicitis (33%), other intraabdominal infection (29%), and abscess (25%). Overall clinical resolution rates were statistically superior for CIP+MET (74%) compared with PIP/TAZO (63%). Corresponding rates in the subgroup suitable for oral therapy were 85% for CIP+MET and 70% for PIP/TAZO. Postsurgical wound infection rates were significantly lower in CIP+MET (11%) versus PIP/TAZO patients (19%). Mean length of stay was 14 days for CIP+MET and 17 days for PIP/TAZO patients.. CIP+MET, initially administered IV and followed by CIP+MET oral therapy, was clinically more effective than IV PIP/TAZO for the treatment of patients with complicated intraabdominal infections.

Topics: Abdomen; Abdominal Abscess; Administration, Oral; Anti-Infective Agents; Appendicitis; Bacterial Infections; Ciprofloxacin; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Injections, Intravenous; Male; Metronidazole; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies

Tazobactam/Piperacillin (TAZ/PIPC) is a newly developed intravenous antibiotics, in which TAZ, a new potent inhibitor of beta-lactamases, is combined with PIPC, a well-established beta-lactam antibiotics, at the ratio of 1:4. In this study, we clinically evaluated efficacy of the drug in 14 pediatric patients with various infections, and pharmacokinetic study was applied to 3 patients. Range of age was from 1-month to 15 1/4-year. Patients consisted of 9 cases of pneumonia, 3 urinary tract infection, 1 acute otitis media, and 1 left sacroiliitis with sepsis. Standard dose of TAZ/PIPC was 50 mg/kg/dose and administered 2-4 times per day with intravenous injection or drip infusion. Two cases of pneumonia were excluded because of non-bacterial infection. Nine causative pathogens including 3 Gram-positive cocci and 6 Gram-negative bacilli were detected in 7 patients, of which 5 Gram-negative strains produced bete-lactamase. All of cases showed 100% of efficacy rate and bacteriological eradication rate. It was noted that beta-lactamase-producing E. coli and B. catarrhalis were eradicated efficiently by TAZ/PIPC, which should be resistant to PIPC alone according to MIC data. Non-serious diarrhea and discomfort of back with nausea were observed in one each patients as side effects. Both of side effects were transient, and improved with anti-diarrheic agent or cessation of the drug, respectively. As abnormal laboratory test results, moderate increases of the eosinophils and platelets counts as well as moderate elevation of the transaminases were observed in 2 separate patients. Pharmacokinetics study showed that Cmax, T1/2, and AUC were similar to the data reported in adult patients. Urinary recovery rate in the first 6 hours also resemble the data from adult patients. Based on above results, TAZ/PIPC is a useful agents pediatric infections by beta-lactamase producing strains also.

Topics: Adolescent; Bacteria; Bacterial Infections; Child; Child, Preschool; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Humans; Infant; Infant, Newborn; Infusions, Intravenous; Injections, Intravenous; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

Pharmacokinetic and clinical evaluation was conducted on the combination drug, tazobactam/piperacillin (TAZ/PIPC, YP-14), of newly developed beta-lactamase inhibitor, tazobactam (TAZ), and antibiotic agent of penicillin group for injections, piperacillin (PIPC), and the following results were obtained. 1. Absorption and excretion Both serum levels of TAZ and PIPC after the intravenous drip infusion for 30 minutes at the dose of 25 mg/kg or 50 mg/kg of TAZ/PIPC showed peaks at the end of the intravenous drip infusion (in 30 minutes after the commencement of the administration) with the levels of 11.93 or 26.05 micrograms/ml for TAZ and 49.80 or 107.50 micrograms/ml for PIPC. The halflife times were 0.51 or 0.67 hours for TAZ and 0.51 or 0.54 hours for PIPC. The serum level of desethyl-piperacillin (DEt-PIPC), an active metabolite of PIPC, showed a peak one hour after the end of the intravenous drip infusion (in 90 minutes after the commencement of the administration) with the level of 0.79 or 1.47 micrograms/ml. On the other hand, cumulative recovery ratios into urine were 41.3% or 40.4% for TAZ and 38.7% or 37.8% for PIPC. The recovery ratio for DEt-PIPC, an active metabolite of PIPC, was 1.9% or 0.3%. 2. Clinical evaluation TAZ/PIPC was administered to 47 cases (pneumonia: 25 cases, bronchitis: 16 cases, cutaneous soft tissue infection: 3 cases, urinary tract infection: 2 cases and lymphadenitis: 1 case). Clinical efficacy evaluation was conducted in 45 cases, excluding one case with bronchitis complicated by measles and other one case with left cervical cellulitis complicated by mumps. Good or more efficacy was observed in the all cases (excellent efficacy: 28 cases and good efficacy: 17 cases). The eradication rate in 31 cases where the pathogenic bacteria were identified and bacteriological efficacy was revealed was 93.5% (29/31 cases). Out of them, bacterial replacement was observed in 5 cases. Decrease in bacteria (including partial eradication) was observed in the remaining 2 cases. Adverse reactions were not reported in any cases. Abnormal values of clinical laboratory examination were reported in 5 cases (increase in platelet count: 2 cases, decrease in leukocyte count: 2 cases and increase in eosinophil count: 1 case). However, there was no case requiring any treatment.

Topics: Bacteria; Bacterial Infections; Child; Child, Preschool; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Humans; Infant; Infusions, Intravenous; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

Pharmacokinetic, bacteriological and clinical studies were performed in pediatrics on tazobactam/piperacillin (TAZ/PIPC), a combined drug of a new beta-lactamase inhibitor tazobactam and piperacillin at a ratio of 1:4. 1. Serum levels and urinary excretions of TAZ, PIPC and desethyl piperacillin (DEt-PIPC), a metabolite of PIPC, after one shot intravenous administration of 50 mg/kg of TAZ/PIPC to two children (6-7 years old) were investigated. The serum TAZ level at 0.08 hour was 50.8-51.0 micrograms/ml after administration. Then TAZ concentrations gradually decreased with half-lives of 0.38-0.45 hour, and reached 1.0-1.4 micrograms/ml after 2 hours and was not detected after 3 hours and 6 hours. Serum PIPC levels at 0.08 hour was 167.0-231.0 micrograms/ml after administration. Then PIPC concentrations gradually decreased with half-lives of 0.41-0.55 hour, and reached 1.2-2.4 micrograms/ml after 3 hours and was not detected after 6 hours. DEt-PIPC was detected slightly in serum. A ratio of TAZ to PIPC was about 1 to 4 in serum at each time. Urinary recovery rates of TAZ in the first 6 hours after administration of TAZ/PIPC were 33.5-90.1% and those of PIPC were 41.9-77.8% and those of DEt-PIPC were 1.5-2.8%. 2. TAZ/PIPC was administered to 27 pediatric patients (their ages ranged between 2 months and 11 years old) with various infections, and clinical and bacteriological effects and adverse reactions were investigated. Single doses were 26.2-55.6 mg/kg, frequencies of administration were 3-4 times a day, and durations of administration were 3 1/3-7 1/3 days, and total dosages were 4.5-33.75 g. Clinical effects were evaluable in 26 cases. Responses were rated as "good" in acute purulent tonsillitis 1 case and acute purulent otitis media 1 case, as "excellent" in acute sinusitis 1 case, as "excellent" in 2 and "good" in 1 out of 3 cases of acute bronchitis, as "excellent" in 13 and "good" 2 out of 15 cases of acute pneumonia, as "excellent" in acute urinary tract infection 2 cases and as "excellent" in acute enteritis in 1 case, acute appendicitis in 1 case and lymphadentis in 1 case. In all cases, the results were rated as "good" or "excellent". Antimicrobial effects against a total of 10 strains identified or assumed to be pathogenic bacteria were evaluated. The 10 strains of bacteria included 4 strains of Streptococcus pneumoniae, 3 strains of Haemophilus influenzae (2 strains beta-lactamase producing), 2 strains of beta-lactamase producing Moraxella cat

Topics: Bacterial Infections; Child; Child, Preschool; Drug Therapy, Combination; Female; Humans; Infant; Infusions, Intravenous; Injections, Intravenous; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

Laboratory and clinical studies on tazobactam/piperacillin (TAZ/PIPC), a combination drug of piperacillin (PIPC) with the new beta-lactamase inhibitor tazobactam (TAZ), were carried out in the field of pediatrics. 1. After intravenous administration of TAZ/PIPC at a dose of 25 mg/kg to one child, the peak plasma levels of TAZ and PIPC were 24.4 micrograms/ml and 119 micrograms/ml respectively after 5 min. The half-lives of TAZ and PIPC were 0.48 and 0.60 hours respectively. Same as 50 mg/kg to two children, the peak plasma levels of TAZ and PIPC were 17.5, 32.2 micrograms/ml and 92.8, 163 micrograms/ml after 5 min. The half-lives of TAZ and PIPC were 0.37, 0.50 hours and 0.51, 0.59 hours. A ratio of TAZ to PIPC was about 1 to 4 in plasma levels. The cumulative urinary recovery rates of TAZ and PIPC in the first 6 hours after intravenous administration were 15.8, 64.9% and 39.8, 53.4%. 2. The antibacterial activity of TAZ/PIPC against clinically isolated organisms was determined. The MICs of TAZ/PIPC were < or = 0.05 microgram/ml against Haemophilus influenzae and Streptococcus pneumoniae and > or = 1.56 micrograms/ml against Escherichia coli, Staphylococcus aureus and Haemophilus parainfluenzae. 3. The clinical efficacy of TAZ/PIPC could be evaluated in 14 patients with various bacterial infections, and was evaluated as "excellent" in 9 patients and as "good" in 5. The overall clinical efficacy rate in 14 cases was 100% and excellent was 64.3%. Bacteriological efficacy rate was 91.7% (10/11). 4. As a side effect, loose stool was observed in one case, no abnormal laboratory test values were observed. It has been concluded that TAZ/PIPC was a useful drug in the field of pediatrics.

Topics: Bacterial Infections; beta-Lactamase Inhibitors; Child, Preschool; Drug Therapy, Combination; Escherichia coli; Female; Haemophilus; Haemophilus influenzae; Humans; Infant; Male; Penicillanic Acid; Penicillin Resistance; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Staphylococcus aureus; Streptococcus pneumoniae; Urinary Tract Infections

Pharmacokinetics, efficacy and safety of tazobactam/piperacillin (TAZ/PIPC), a new beta-lactamase inhibitor combined with a penicillin antibiotic, were studied in pediatrics and the following results were obtained. 1) Serum concentration and urinary excretion of TAZ/PIPC after intravenous administration at a dose of 46 mg/kg to one child were investigated. Serum half-lives were 0.5 hours for TAZ and 0.6 hours for PIPC, while the urinary recovery rates in the first 6 hours after administration, were 61.6% and 56.3% respectively. 2) TAZ/PIPC was administered at a dose of 46.0-73.5 mg/kg t.i.d. for 3-13 days to 10 patients, 6 with respiratory infection, 1 with pharyngotonsillitis, 1 with pertussis and 2 with soft tissue infection of skin. Clinical response were excellent in 5 cases and good in 5 cases, and the efficacy rate was 100%. Bacteriologically, 2 strains (Staphylococcus aureus and Streptococcus pyogenes) isolated from 2 patients were eradicated after the treatment. As for adverse reaction, mild skin rash was observed in 1 case but disappeared within 2 days after withdrawal of the drug. As for abnormal laboratory test results decrease in neutrophiles and increase in eosinophiles in each 1 case were observed, which were, however, normalized after administration. From the above results, tazobactam/piperacillin was considered to be a useful antibiotic in the pediatric field.

Topics: Bacterial Infections; beta-Lactamase Inhibitors; Child; Drug Therapy, Combination; Female; Humans; Infant; Male; Penicillanic Acid; Pharyngitis; Piperacillin; Piperacillin, Tazobactam Drug Combination; Respiratory Tract Infections; Staphylococcus aureus; Tonsillitis; Whooping Cough

A drug susceptibility test of the combination drug TAZ/PIPC, which consists of a newly developed beta-lactamase inhibitor, tazobactam (TAZ), and one of penicillin antibiotics, piperacillin (PIPC), with combination ratio of 1:4 in potency, was conducted with stock strains and clinical isolates. The clinical efficacy and safety of its injection was also evaluated in children with a variety of infectious diseases. The results were as follows: 1. In susceptibility test, 114 strains from 4 species of stock strains were treated with 8 drugs, that is, TAZ/PIPC, PIPC, penicillin G (PCG), ampicillin (ABPC), cefotiam (CTM), cefotaxime (CTX), ceftazidime (CAZ), and sulbactam/cefoperazone (SBT/CPZ). Of three clinically isolated species from patients, Staphylococcus aureus (S. aureus) was treated with TAZ/PIPC, PIPC, methicillin (DMPPC), CTM, CTX, and SBT/CPZ, and the others were treated with the same drugs except for DMPPC. The MICs were measured for these bacterial strains inoculated at the concentration of 10(6) CFU/ml. The MIC90 values of TAZ/PIPC against 45 strains of Streptococcus pyogenes (S. pyogenes), one of the stock cultures of Gram-positive cocci, were 0.05 microgram/ml and similar to those of PIPC, CTM, CAZ, and SBT/CPZ. The MICs of TAZ/PIPC for 28 strains of Streptococcus agalactiae (S. agalactiae) were 0.39 microgram/ml and similar to those of PIPC, CTM, CAZ, and SBT/CPZ. As for Gram-negative bacilli, the MIC90 of TAZ/PIPC against 10 strains of Bordetella pertussis (B. pertussis) were 0.10 microgram/ml and similar to those of PIPC. The MIC90 of TAZ/PIPC against 31 strains of Haemophilus influenzae (H. influenzae) were 0.05 microgram/ml and similar to those of PIPC, CTX, and SBT/CPZ. Regarding Gram-positive cocci isolated from patients received this combination drug, the MIC90 of TAZ/PIPC against 2 strains of S. aureus, a non beta-lactamase producing strain and a low-beta-lactamase producing strain, were 0.78 microgram/ml and 3.1 micrograms/ml, respectively; the former value was similar to those of PIPC, DMPPC, CTM, and CTX, and the latter was similar to those of PIPC, DMPPC, CTX, and SBT/CPZ. Of 4 strains of Streptococcus pneumoniae, 2 strains were inhibited at 0.05 microgram/ml, and the others at 1.56 micrograms/ml; both values were similar to those of PIPC, SBT/CPZ. As for Gram-negative bacilli, 6 of 7 strains of H. influenzae did not produce beta-lactamase and 1 strain was a high producer. The MICs of TAZ/PIPC against beta-lactamase nonproducing stra

Topics: Acute Disease; Bacterial Infections; beta-Lactamase Inhibitors; Bordetella pertussis; Bronchitis; Child; Child, Preschool; Drug Therapy, Combination; Female; Haemophilus influenzae; Humans; Infant; Lymphadenitis; Male; Otitis Media, Suppurative; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Staphylococcus aureus; Streptococcus agalactiae; Streptococcus pneumoniae; Streptococcus pyogenes; Urinary Tract Infections; Whooping Cough

Fifteen patients with severe bacterial infection (12 with pneumonia) that developed in the resuscitation unit were subjected to the empirical monotherapy with piperacillin/tazobactam (P/T) or tazocin under an open randomized controlled experiment. P/T was administered intravenously in a dose of 4.5 g every 8 hours for 5 to 12 days (9.3 days on the average). When the monotherapy was not sufficiently efficient the patients were additionally treated with amikacin administered intravenously in a dose of 0.5 g every 8-12 hours. The favourable effect was observed in 14 patients (93 per cent). 7 of them were treated with P/T alone and 7 were treated with P/T in combination with amikacin. The primary pathogens were eradicated in 8 (73 per cent) out of the 11 patients treated with P/T alone. Before the treatment 34 microbial strains were isolated from the patients. 77 per cent of them were susceptible to P/T. The treatment with P/T resulted in eradication of 27 bacterial strains (79 per cent) including 67 per cent of gram-positive organisms and 86 per cent of gram-negative organisms. The adverse effects were recorded in 1 patient on the 6th day of the treatment: skin eruption and pruritus that required the treatment discontinuation. The results showed that the use of P/T in the initial empirical monotherapy of infections in patients under resuscitation conditions could be efficient.

Topics: Adult; Bacterial Infections; Drug Therapy, Combination; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Hospital Departments; Humans; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Resuscitation; Treatment Outcome

The effect of the monotherapy with piperacillin/tazobactam (P/T) or tazocin on microflora of the mucous membranes of the nose and pharynx of 33 patients and the contents of the large intestine of 21 patients as well as on the immunological aspects (cellular and humoral factors) of the antiinfectious resistance systems (AIRS) in patients with abdominal cavity infection (ACI) was studied. Before the treatment serious impairment of the AIRS in all the patients was observed. The P/T monotherapy in a daily dose of 12/1.5 g at the average for 10 days had no unfavourable effect on the indices characterizing the phagocytic function of the neutrophils in the incompleted and completed variants, on the immunocompetent cells, hemolytic complement and the levels of IgM, IgG and IgA. No significant effect of the treatment on the mucosal microflora on the whole was detected. However, Neisseria spp. and Corynebacterium pseudodiphtheriticum were eradicated in the pharynx while the number of the Klebsiella pneumoniae [symbol: see text] Escherichia coli isolates from the pharynx mucosa increased. The number of the bifidobacteria in the contents of the large intestine significantly lowered while the number of the hemolyzing forms of enterococci and stapylococci increased. The investigation of the AIRS immunological aspects in the patient groups of different total (clinicomorphological) efficacy showed that the neutrophil phagocytic function was the efficacy predictor and P/T in its turn had an immunomodulating effect on the neutrophil phagocytic activity in the patients with ACI.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Infections; Drug Therapy, Combination; Humans; Immunity, Innate; Microbial Sensitivity Tests; Middle Aged; Penicillanic Acid; Peritoneal Diseases; Piperacillin; Piperacillin, Tazobactam Drug Combination

Concerned about the inactivation of piperacillin by beta-lactamase and the risk of aminoglycoside-induced nephrotoxicity and clindamycin-induced enterocolitis, we conducted the following phase III clinical trial.. Between November 1991 and March 1993, 77 surgical patients with intraabdominal infections were enrolled and randomly assigned in a 3:2 ratio to receive either piperacillin/tazobactam or clindamycin plus gentamicin to compare safety, tolerance and efficacy between both two treatment groups.. There were 76 clinically and 50 bacteriologically evaluable patients with 80 isolated pathogens. The demographic data were comparable in both groups. There was no statistically significant difference of clinical response at any time-point of treatment, with 97.8% favorable clinical response rate in piperacillin tazobactam group and 96.6% in clindamycin plus gentamicin group at endpoint. The bacteriological eradication rates were similar, with 97.7% in piperacillin/tazobactam group and 94.4% in clindamycin plus gentamicin group at pathogen level, and 96.7% in piperacillin/tazobactam group and 95.0% in clindamycin plus gentamicin group at patient level. By susceptibility tests, only 3 (4%) isolated pathogens were resistant to piperacillin/tazobactam, which was much superior to the use of piperacillin, clindamycin or gentamicin alone in antimicrobial activity. The piperacillin tazobactam-related adverse experiences included 1 (2.1%) urticaria and 2 (4.3%) diarrhea. However, there were no significant differences in the adverse experiences between these two groups.. This study has demonstrated that piperacillin/tazobactam is comparable with clindamycin plus gentamicin in efficacy, safety and tolerance in the treatment of surgical patients with intra-abdominal infections. The combination of piperacillin/tazobactam could potentially be the treatment of choice in adjunt to surgical management in intra-abdominal infection.

Topics: Abdomen; Bacterial Infections; Clindamycin; Drug Therapy, Combination; Female; Gentamicins; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

Ventilator-associated pneumonia (VAP) is one of the major hospital-acquired infections and the emergence of bacterial resistance is common among patients in the intensive care units (ICUs). The aim of the study is to identify the common bacterial pathogen isolated from an endotracheal (ET) aspirate and its antibiotic susceptibility pattern.. A prospective analytical study was carried out in a tertiary care hospital for a period of 1 year. All ET aspirate sample sent to the microbiology laboratory was processed and identified by standard biochemical tests and antibiotic sensitivity was by disk diffusion method as per Clinical and Laboratory Standards Institute (CLSI) guidelines.. Of the total 217 samples studied, 85 (39.17.1%) were culture sterile and 132 (60.82%) showed culture positive. Among 132 isolates, the predominant organism was Acinetobacter baumannii (36.36%) followed by Klebsiella pneumoniae (24.24%) and Pseudomonas aeruginosa (20.45%). We have reported a higher percentage of resistance among the isolated gram-negative bacilli to carbapenems, aminoglycosides, and third-generation cephalosporins, with increased sensitivity to piperacillin-tazobactam and cefoperazone-sulbactam.. In our study, A. baumannii was the predominantly isolated gram-negative bacilli followed by K. pneumoniae and P. aeruginosa. One of the rising concerns to hospital-acquired respiratory pathogens is the surge of multidrug resistance patterns. Hence, strict adherence to antibiotic policy and appropriate use according to the guidelines will save the use of drugs in the future in life-threatening conditions.

Topics: Anti-Bacterial Agents; Bacterial Infections; Cefoperazone; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Pseudomonas aeruginosa

Topics: Adult; Anti-Bacterial Agents; Bacterial Infections; Bronchopulmonary Sequestration; Humans; Ligation; Lung Diseases; Male; Piperacillin, Tazobactam Drug Combination; Thoracoscopy

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. Bacterial co-infections are associated with unfavourable outcomes in respiratory viral infections; however, microbiological and antibiotic data related to COVID-19 are sparse. Adequate use of antibiotics in line with antibiotic stewardship (ABS) principles is warranted during the pandemic. We performed a retrospective study of clinical and microbiological characteristics of 140 COVID-19 patients admitted between February and April 2020 to a German University hospital, with a focus on bacterial co-infections and antimicrobial therapy. The final date of follow-up was 6 May 2020. Clinical data of 140 COVID-19 patients were recorded: The median age was 63.5 (range 17-99) years; 64% were males. According to the implemented local ABS guidelines, the most commonly used antibiotic regimen was ampicillin/sulbactam (41.5%) with a median duration of 6 (range 1-13) days. Urinary antigen tests for Legionella pneumophila and Streptococcus peumoniae were negative in all cases. In critically ill patients admitted to intensive care units (n = 50), co-infections with Enterobacterales (34.0%) and Aspergillus fumigatus (18.0%) were detected. Blood cultures collected at admission showed a diagnostic yield of 4.2%. Bacterial and fungal co-infections are rare in COVID-19 patients and are mainly prevalent in critically ill patients. Further studies are needed to assess the impact of antimicrobial therapy on therapeutic outcome in COVID-19 patients to prevent antimicrobial overuse. ABS guidelines could help in optimising the management of COVID-19. Investigation of microbial patterns of infectious complications in critically ill COVID-19 patients is also required.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ampicillin; Anti-Bacterial Agents; Antifungal Agents; Antimicrobial Stewardship; Aspergillosis; Azithromycin; Bacterial Infections; Cohort Studies; Coinfection; COVID-19; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Germany; Humans; Klebsiella Infections; Linezolid; Male; Meropenem; Middle Aged; Piperacillin, Tazobactam Drug Combination; Practice Patterns, Physicians'; Retrospective Studies; SARS-CoV-2; Staphylococcal Infections; Streptococcal Infections; Sulbactam; Vancomycin; Young Adult

With rising antibiotic resistance, alternatives to carbapenems are needed for acute cholangitis (AC). Temocillin reaches high biliary concentrations with limited impact on microbiota. We retrospectively included 140 AC episodes and assessed the efficacy of temocillin using microbiology susceptibility testing from blood cultures. Considering all bacteria collected by episode, resistance to temocillin, PIP/TAZ and 3GC occurred in 27/140 (26%), 32 (22.8%) and 31 (22%) episodes, respectively (p = 0.7). After documentation, temocillin could have spared PIP/TAZ or carbapenems in 14/26 and 4/11 episodes. Temocillin may constitute an alternative treatment after microbiological documentation by sparing carbapenems and/or PIP/TAZ, but not as an empirical therapeutic option.

Topics: Anti-Bacterial Agents; Bacterial Infections; Cholangitis; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Penicillins; Piperacillin, Tazobactam Drug Combination; Retrospective Studies

Piperacillin is a β-lactam antimicrobial frequently used in critically ill patients with acute kidney injury treated with continuous renal replacement therapy (CRRT). However, data regarding piperacillin tissue concentrations in this patient population are limited. A prospective observational study was conducted of free piperacillin concentrations during a single 8-h dosing interval in plasma (8 samples) and subcutaneous tissue (SCT) (13 samples), in 10 patients treated with CRRT following piperacillin 4 g given every 8 h as intermittent administration over 3 min.. A population pharmacokinetic model was developed using NONMEM 7.4.3, to simulate alternative administration modes and dosing regimens. SCT concentrations were obtained using microdialysis. Piperacillin concentrations were compared to the clinical breakpoint minimum inhibitory concentration (MIC) for Pseudomonas aeruginosa (16 mg/l), with evaluation of the following pharmacokinetic/pharmacodynamics targets: 50% fT > 1 × MIC, 100% fT > 1 × MIC, and 100% fT > 4 × MIC.. SCT concentrations were generally lower than plasma concentrations. For the target of 50% free time (fT) > 1 × MIC and 100% fT > 1 × MIC, piperacillin 4 g every 8 h resulted in probability of target attainment (PTA) >90% in both plasma and SCT. PTA > 90% for the target of 100% fT > 4 × MIC was only achieved for continuous infusion.. Piperacillin 4 g every 8 h is likely to provide sufficient exposure in both plasma and SCT to treat P.aeruginosa infections in critically ill patients on CRRT, given that targets of 50% fT > 1 × MIC or 100% fT > 1 × MIC are adequate. However, if a more aggressive target of 100% fT > 4 × MIC is adopted, continuous infusion is needed.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Computer Simulation; Continuous Renal Replacement Therapy; Female; Humans; Male; Models, Biological; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Subcutaneous Tissue

Infection is a major complication for patients with haematological malignancies. It is important to better understand the use of antimicrobial agents and antibiotic resistance for appropriate treatment and prevention of drug resistance. However, very few multi-centre analyses have focused on the use of antimicrobial agents and antibiotic resistance have been carried out in Japan. This study aimed to describe the characteristics of the use of antimicrobial agents and antibiotic resistance in patients with haematological malignancies.. We conducted a cross-sectional study using administrative claims data and antimicrobial susceptibility data in Japan. We included patients diagnosed with haematological malignancies, who were hospitalized in a haematology ward between 1 April 2015 and 30 September 2017 in 37 hospitals. Descriptive statistics were used to summarize patient characteristics, antimicrobial utilization, bacterial infections, and antibiotic resistance.. In total, 8064 patients were included. Non-Hodgkin lymphoma (50.0%) was the most common malignancy. The broad-spectrum antibiotics displayed a following antimicrobial use density (AUD): cefepime (156.7), carbapenems (104.8), and piperacillin/tazobactam (28.4). In particular, patients with lymphoid leukaemia, myeloid leukaemia, or myelodysplastic syndromes presented a higher AUD than those with Hodgkin lymphoma, non-Hodgkin lymphoma, or multiple myeloma. The most frequent bacterial species in our study cohort was Escherichia coli (9.4%), and this trend was also observed in blood specimens. Fluoroquinolone-resistant E. coli (3.6%) was the most frequently observed antibiotic-resistant strain, while other antibiotic-resistant strains were rare.. Broad-spectrum antibiotics were common in patients with haematological malignancies in Japan; however, antibiotic-resistant bacteria including carbapenem-resistant or multidrug-resistant bacteria were infrequent. Our results provide nationwide, cross-sectional insight into the use of antimicrobial agents, prevalence of bacteria, and antibiotic resistance, demonstrating differences in antimicrobial utilization among different haematological diseases.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Carbapenems; Cefepime; Cross-Sectional Studies; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Escherichia coli; Female; Hematologic Neoplasms; Humans; Japan; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Young Adult

Empirical models to predict β-lactam pharmacokinetics (PK) using information from routine aminoglycoside therapeutic drug monitoring (TDM) have been proposed for critically ill patients; however, no such models exist for patients with cystic fibrosis (CF).. To investigate whether PK parameters of tobramycin could be used to predict those of piperacillin.. A non-interventional, open-label PK study was conducted in hospitalized adults treated with piperacillin/tazobactam and tobramycin for acute pulmonary exacerbations of CF. Six serum samples per patient were collected and analysed. One- and two-compartment population PK models with linear, Michaelis-Menten or mixed elimination were evaluated for both drugs within the PmetricsTM package for R. Models were developed and compared iteratively using the log-likelihood and Akaike information criterion (AIC) objective functions.. Nine primarily female (n = 8) and Caucasian (100%) adult CF patients were enrolled. The median (IQR) age, height, weight and serum creatinine of included patients was 31 (27-32) years, 51.4 (49.9-55.8) kg, 162.6 (160.0-165.1)  cm and 0.6 (0.5-0.6) mg/dL, respectively. The final model with the lowest objective function values consisted of one compartment with first-order elimination for tobramycin and two compartments with mixed-order elimination for piperacillin with the elimination rate constant of piperacillin modelled as a linear function of the elimination rate constant of tobramycin.. A relationship was identified between the elimination rate constants of tobramycin and piperacillin. Validation of this relationship in larger studies of adult patients with CF is needed before application to the precision dosing of piperacillin/tazobactam in this patient population.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; beta-Lactamase Inhibitors; Cystic Fibrosis; Female; Humans; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Tobramycin; Young Adult

The purpose of this study was to investigate the association between prophylactic antibiotic administration (PAA) and postoperative infection after radical cystectomy with urinary diversion in patients with invasive bladder cancer.. Forty-nine consecutive cases were analyzed prospectively. Postoperative infections were categorized as surgical site infection (SSI) and remote infection (RI). We used the antibiotics tazobactam/piperacillin (TAZ/PIPC) as PAA (48 h).. A total of 18 (36.7%) patients had postoperative infections, 4/18 (22.2%) patients had wound infections, and 12/18 (66.7%) patients had RI. In the risk factor study for SSI and RI occurrences, we found that the surgical time was significantly shorter in the non-infection group (p = 0.031). Taken together, these results suggest that TAZ/PIPC with shorter PAA duration (48 h) might lead to a lower rate of postoperative infections.. Our data showed that PAA with TAZ/PIPC with a shorter duration PAA (48 h) might be recommended for RC with urinary diversion. We found that the surgical time was significantly shorter in the non-infection group. A prospective study based on our data is desirable to establish or revise PAA strategy for prophylactic medication to prevent postoperative infection after RC with urinary diversion.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Infections; Cystectomy; Female; Humans; Male; Middle Aged; Neoplasm Invasiveness; Piperacillin, Tazobactam Drug Combination; Postoperative Complications; Postoperative Period; Prospective Studies; Stents; Surgical Wound Infection; Urinary Bladder Neoplasms; Urinary Diversion

Piperacillin is a broad spectrum beta-lactam antibiotic used in combination with tazobactam for hospital-related bacterial infections. The reconstituted solutions must respect the sub-visible and visible particles specifications. It was claimed that the reformulation containing EDTA/sodium citrate was able to control the formation of an insoluble impurity responsible for the formation of particulate matter observed using Ringer Lactate as diluent. The nature of the impurities formed during the degradative process of piperacillin/tazobactam combination has been herein investigated, by exploring the effect of added excipients and pH variations. The exact structure of the isolated dimeric impurity, the penicilloic acid-piperacillin dimer, was determined through complete characterization, allowing to propose a novel degradative general pathway for beta-lactam antibiotics. The presence of EDTA resulted unnecessary to contain the formation of the insoluble impurity, since the use of sodium citrate alone allowed to avoid this drawback. Finally, the proposed mechanism was successfully applied to the design of a novel, easy and high purity procedure for the synthesis of the acetylated penicilloic acid, known related substance of piperacillin.

Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Penicillanic Acid; Penicillins; Piperacillin; Piperacillin, Tazobactam Drug Combination; Tazobactam

The β-lactam antibiotic piperacillin (in combination with tazobactam) is commonly chosen for empirical treatment of suspected bacterial infections. However, pharmacokinetic variability among patient populations and across ages leads to uncertainty when selecting a dosing regimen to achieve an appropriate pharmacodynamic target.. To guide dosing by establishing a population pharmacokinetic model for unbound piperacillin in febrile children receiving cancer chemotherapy, and to assess pharmacokinetic/pharmacodynamic target attainment (100% fT > 1×MIC and 50% fT > 4×MIC) and resultant exposure, across body weights.. Forty-three children admitted for 89 febrile episodes contributed 482 samples to the pharmacokinetic analysis. The typical doses required for target attainment were compared for various dosing regimens, in particular prolonged infusions, across MICs and body weights.. A two-compartment model with inter-fever-episode variability in CL, and body weight included through allometry, described the data. A high CL of 15.4 L/h (70 kg) combined with high glomerular filtration rate (GFR) values indicated rapid elimination and hyperfiltration. The target of 50% fT > 4×MIC was achieved for an MIC of 4.0 mg/L in a typical patient with extended infusions of 2-3 (q6h) or 3-4 (q8h) h, at or below the standard adult dose (75 and 100 mg/kg/dose for q6h and q8h, respectively). Higher doses or continuous infusion were needed to achieve 100% fT > 1×MIC due to the rapid piperacillin elimination.. The licensed dose for children with febrile neutropenia (80 mg/kg q6h as a 30 min infusion) performs poorly for attainment of fT>MIC pharmacokinetic/pharmacodynamic targets. Given the population pharmacokinetic profile, feasible dosing regimens with reasonable exposure are continuous infusion (100% fT > 1×MIC) or prolonged infusions (50% fT > 4×MIC).

Topics: Adolescent; Anti-Bacterial Agents; Bacterial Infections; Body Weight; Child; Child, Preschool; Female; Fever; Glomerular Filtration Rate; Humans; Infant; Male; Microbial Sensitivity Tests; Neoplasms; Piperacillin; Piperacillin, Tazobactam Drug Combination; Tazobactam

We sought to evaluate clinical outcomes of intensive care unit (ICU) patients following a hospital-wide initiative of prolonged piperacillin/tazobactam (PIP/TAZ) infusion.. Retrospective observational study of patients >18 years old who was hospitalized in the ICU receiving PIP/TAZ for >72 hours during the preimplementation (June 1, 2010 to May 31, 2011) and postimplementation (July 7, 2011 to June 30, 2014) periods.. There were 124 and 429 patients who met inclusion criteria with average age of 54.3 and 56.9 years, and average duration of PIP/TAZ therapy was 6.1 ± 2.8 days and 5.9 ± 3.4 days in the pre- and postimplementation period, respectively. Intensive care unit and hospital length of stay (LOS) following initiation of PIP/TAZ were 8.0 ± 8.4 days versus 6.4 ± 6.8 days and 26.3 ± 22.8 days versus 20.4 ± 16.1 days among patients in the pre- and postimplementation periods, respectively. Compared to patients who received intermittent PIP/TAZ infusion, the adjusted difference in ICU and hospital LOS was 0.6 ± 0.8 days (95% confidence interval [CI]: -0.9 to 2.1 days) and 5.6 ± 2.1 days (95% CI: 1.4 - 9.7 days) shorter among patients who received prolonged PIP/TAZ infusion. At hospital discharge, 19 (15.3%) intermittent infusion and 74 (17.2%) prolonged infusion recipients had died. In comparison to intermittent infusion recipients, the adjusted odds ratio for mortality was 1.17 (95% CI: 0.65-2.1) with prolonged infusion.. Our study demonstrated a reduction in hospital LOS with prolonged PIP/TAZ infusion among critically ill patients. Randomized trials are needed to further validate these findings.

Topics: Aged; Anti-Bacterial Agents; Bacterial Infections; Critical Illness; Female; Hospital Mortality; Humans; Infusions, Intravenous; Intensive Care Units; Length of Stay; Linear Models; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies

In older adults, few studies confirm that adequate concentrations of antibiotics are achieved using current dosage regimens of intravenous β-lactam antibiotics. Our objective was to investigate trough concentrations of cefotaxime, meropenem, and piperacillin in older adults hospitalized with infection. We included 102 patients above 70 years of age. Total trough antibiotic concentrations were measured and related to suggested target intervals. Information on antibiotic dose, patient characteristics, and 28-day outcomes were collected from medical records and regression models were fitted. Trough concentrations for all three antibiotics exhibited considerable variation. Mean total trough concentrations for cefotaxime, meropenem, and piperacillin were 6.5 mg/L (range 0-44), 3.4 mg/L (range 0-11), and 30.2 mg/L (range 1.2-131), respectively. When a target range of non-species-related breakpoint - 5× non-species-related breakpoint was applied, only 36% of patients had both values within the target range. Regression models revealed that severe sepsis was associated with varying concentration levels and increasing age and diminishing kidney function with high concentration levels. The study was not powered to demonstrate consequences in clinical outcomes. Conclusively, in older adults treated with cefotaxime, meropenem, or piperacillin-tazobactam, trough antibiotic concentrations varied considerably. Better predictors to guide dosing regimens of β-lactam antibiotics or increased use of therapeutic drug monitoring are potential ways to address such variations.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Bacterial Infections; beta-Lactams; Cefotaxime; Drug Monitoring; Female; Humans; Length of Stay; Male; Meropenem; Patient Readmission; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Sepsis; Sweden; Thienamycins

Patients often receive broad-spectrum antibiotics for nosocomial infections commonly with activity against Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus. Previous retrospective and/or single-center studies have suggested that the combination of vancomycin and piperacillin/tazobactam might be associated with an increased risk of acute kidney injury.. To compare the incidence of nephrotoxicity in patients receiving intravenous vancomycin in combination with cefepime, meropenem, or piperacillin/tazobactam.. This was a prospective, multicenter observational study of patients receiving vancomycin in combination with piperacillin/tazobactam versus cefepime or meropenem. Adult patients 18 years of age or older who were hospitalized and received 72 or more hours of intravenous vancomycin and 72 hours or more of cefepime, meropenem, or piperacillin/tazobactam were eligible. Patient and medication characteristics were examined for the 242 patients included.. The incidence of acute kidney injury for patients treated with vancomycin and piperacillin/tazobactam was significantly higher than for those treated with vancomycin and cefepime or meropenem, 29.8% versus 8.8%, respectively, P < 0.001. Binary logistic regression demonstrated that patients receiving vancomycin and piperacillin/tazobactam were 6.7 times more likely to develop acute kidney injury compared with the other cohort.. The combination of vancomycin with piperacillin/tazobactam significantly increases the risk of acute kidney injury compared with other broad-spectrum antibiotic combinations. Clinicians should be vigilant when employing this regimen.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Cefepime; Drug Therapy, Combination; Female; Humans; Male; Meropenem; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

Gram negative anaerobic organisms are important pathogens in a range of clinical infections, and susceptibility testing is not commonly performed in the microbiology laboratory. We performed anaerobic susceptibility testing on 70 clinically relevant Gram negative anaerobes isolated from routine cultures in a busy diagnostic laboratory which were identified by MALDI-TOF mass spectrometry (MALDI-TOF MS). The susceptibility testing was performed by two methods: Sensititre trays (ThermoFisher Scientific) against 15 different antibiotics, and Etests (bioMérieux) against five clinically relevant antibiotics (metronidazole, piperacillin-tazobactam, amoxicillin-clavulanate, meropenem and clindamycin). We found that all isolates were susceptible to metronidazole, and overall susceptibility to commonly used antibiotics such as piperacillin-tazobactam and amoxicillin-clavulanate was high (93-100% and 89-100%, respectively). Two isolates of Bacteroides fragilis were resistant to both broad spectrum β-lactams and carbapenems. Comparing the two methods, using Sensititre broth microdilution as gold standard, there was high categorical agreement (92-100%). Antibiograms provide useful information for clinicians when choosing antimicrobials for infections caused by anaerobic organisms. This study has shown that in our area, use of metronidazole as a broad spectrum anti-anaerobic agent remains appropriate. Anaerobic susceptibility testing is also important to perform in individual clinical isolates, especially from sterile sites or in pure culture. The emergence of broad spectrum β-lactam and carbapenem resistance in clinical isolates of Bacteroides fragilis is of concern and will require further monitoring. The Etest method was considered superior to Sensititre trays given that the higher inoculum used may allow demonstration of heteroresistance, anaerobiasis can be maintained during setup, lower failure rates, and the ability to select only the antibiotics required.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Infections; Carbapenems; Disk Diffusion Antimicrobial Tests; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

Topics: Anti-Bacterial Agents; Bacterial Infections; beta-Lactams; Costs and Cost Analysis; Home Infusion Therapy; Humans; Infusions, Intravenous; Outpatients; Penicillins; Piperacillin, Tazobactam Drug Combination; Treatment Outcome; United Kingdom

In 2015, our center replaced vancomycin with linezolid for the postoperative empirical treatment of osteoarticular infections (OAI).. To assess the bacteriological relevance of linezolid for orthopedic postoperative probabilistic antibiotic therapy.. Analysis of an observational cohort of patients empirically treated with a combination of linezolid and piperacillin/tazobactam during the immediate postoperative stage for an OAI between July 1. Seventy-seven of 126 patients who received a probabilistic postoperative combination of linezolid with piperacillin/tazobactam had microbiological proof of infection. Sixty-six of 77 OAI involved material, including an osteosynthesis in 45 cases (68%) and prosthesis in 21 cases (32%). Infection was due to Gram-positive bacteria in 62 cases (80.5%), mostly S. aureus (n=32, 41.6%), and S. epidermidis (n=14, 18.2%) accounting for 74.2% of Gram-positive bacteria. Among 14 OAI due to S. epidermidis, 11 (78.6%) were due to methicillin-resistant strains. All the S. aureus and S. epidermidis strains were susceptible to linezolid (MICs ≤ 4 mg/L), except in one patient previously treated with linezolid who was infected with a linezolid-resistant S. epidermidis strain (MIC > 256 mg/L).. Linezolid can be used empirically in postoperative antibiotic therapy of OAI before obtaining definitive microbial results. Although linezolid resistance is rare in this population, previous oxazolidinone treatment should be documented before initiation of probabilistic postoperative treatment to highlight potential linezolid resistance.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Female; France; Gram-Positive Bacteria; Humans; Linezolid; Male; Microbial Sensitivity Tests; Middle Aged; Osteoarthritis; Piperacillin, Tazobactam Drug Combination; Prosthesis-Related Infections; Retrospective Studies; Surgical Wound Infection; Vancomycin

The objective was to determine the effectiveness of two piperacillin-tazobactam molecules in terms of all-cause mortality, mortality by infection, and hospital stay.. A cohort study was performed involving patients treated with piperacillin-tazobactam at a clinic in Colombia. The patients were divided into those who received the innovator piperacillin-tazobactam (from July to December 2014) and those who received the generic piperacillin-tazobactam (from January to June 2015). Socio-demographic, clinical (all-cause mortality, death by infection, days of hospitalization), microbiological, pharmacological, and comorbidity variables were evaluated. Multivariate analyses were performed.. A total of 279 patients were included: 140 treated with the innovator piperacillin-tazobactam and 139 with the generic piperacillin-tazobactam. The median age was 63 years, and 56% of the patients were male. There was no statistically significant difference in death from all causes (22.9% vs. 14.4%, p=0.069), death by infection (7.9 vs. 10.8%, p=0.399), or hospital stay (18.1±16.2 vs. 15.7±11.6 days, p=0.178) between the innovator and generic piperacillin-tazobactam, respectively.. The generic piperacillin-tazobactam was equivalent to the innovator piperacillin-tazobactam with regards to all-cause mortality, mortality by infection, hospital stay, and safety, and at a lower cost, which may be useful for decision-makers in hospitals.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Cohort Studies; Female; Humans; Length of Stay; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination

Ambulatory therapy in low-risk patients with cancer, fever, and neutropenia seems to be a secure and effective alternative. This study aimed to compare the effectiveness and safety of the antimicrobial treatment in early discharge vs. in-hospital treatment in children with cancer and febrile neutropenia (FN) with low risk of invasive bacterial infection (IBI).. Quasi-experimental design with a historical cohort control group. Children with cancer during an episode of FN and low risk of IBI were included. The control group were inpatient children that received intravenous piperacillin/tazobactam. The experimental group was early discharge patients, who received 48 h of IV treatment and were switched to oral treatment. Outcomes: fever resolution, readmissions, and mortality.. Eighty low-risk FN episodes were included; the median age was 6 years old (2.6-11 years), and 43 (54%) were female. Main diagnoses were solid tumors (52 patients) and leukemia or lymphoma (28 patients). Forty-three patients received in-hospital treatment, and 37 were selected for early discharge (31 patients received ciprofloxacin and six received amoxicillin/clavulanate). Two patients were readmitted, one due to a relapse of fever with tumor progression and the other due to epistaxis. Adverse effects occurred in 21.6% of the early discharge group and 12% of the inpatient treatment group (p = 0.04).. Early discharge in pediatric patients with cancer, fever, and neutropenia is an acceptable and safe alternative for low-risk patients.. El tratamiento ambulatorio en pacientes con cáncer, fiebre y neutropenia de bajo riesgo parece ser una alternativa segura y efectiva. El objetivo de este trabajo fue comparar la efectividad y la seguridad del tratamiento antimicrobiano en la modalidad de egreso temprano vs. el tratamiento intrahospitalario en niños con cáncer y neutropenia febril (NF), con bajo riesgo de infección bacteriana invasiva (IBI).. Diseño cuasi-experimental con un grupo control histórico. Se incluyeron niños con cáncer durante un episodio de NF con bajo riesgo de IBI. El grupo control fue constituido por pacientes que recibieron tratamiento hospitalario con piperacilina-tazobactam intravenosa. Los pacientes en el grupo de egreso temprano recibieron 48 horas de tratamiento intravenoso y egresaron con antimicrobianos por vía oral. Desenlaces: resolución de la fiebre, reingreso al hospital y muerte.. Se incluyeron 80 pacientes con NF de bajo riesgo; la mediana de edad fue de 6 años; 43 pacientes (54%) eran de sexo femenino. Los diagnósticos principales fueron tumores sólidos (52) y leucemia o linfoma (28). Cuarenta y tres pacientes recibieron tratamiento hospitalario y 37 fueron seleccionados para egreso temprano. En el grupo de egreso temprano, 31 pacientes recibieron ciprofloxacino y 6 recibieron amoxicilina-clavulanato. Dos pacientes reingresaron, uno por fiebre secundaria a progresión tumoral y otro por epistaxis. Los efectos adversos se presentaron en el 21.6% de los pacientes en el grupo de egreso temprano y en el 12% del grupo de tratamiento hospitalario (p = 0.04).. El egreso temprano para niños con cáncer y NF de bajo riesgo es una alternativa aceptable y segura.

Topics: Ambulatory Care; Anti-Bacterial Agents; Bacterial Infections; Case-Control Studies; Chemotherapy-Induced Febrile Neutropenia; Child; Child, Preschool; Female; Hospitalization; Hospitals, Pediatric; Humans; Male; Mexico; Neoplasms; Patient Discharge; Piperacillin, Tazobactam Drug Combination; Risk; Tertiary Care Centers

To characterize the population pharmacokinetics of piperacillin and tazobactam in critically ill infants and children, in order to develop an evidence-based dosing regimen.. This pharmacokinetic study enrolled patients admitted to the paediatric ICU for whom intravenous piperacillin/tazobactam (8:1 ratio) was indicated (75 mg/kg every 6 h based on piperacillin). Piperacillin/tazobactam concentrations were measured by an LC-MS/MS method. Pharmacokinetic data were analysed using non-linear mixed effects modelling.. Piperacillin and tazobactam blood samples were collected from 47 patients (median age 2.83 years; range 2 months to 15 years). Piperacillin and tazobactam disposition was best described by a two-compartment model that included allometric scaling and a maturation function to account for the effect of growth and age. Mean clearance estimates for piperacillin and tazobactam were 4.00 and 3.01 L/h for a child of 14 kg. Monte Carlo simulations showed that an intermittent infusion of 75 mg/kg (based on piperacillin) every 4 h over 2 h, 100 mg/kg every 4 h given over 1 h or a loading dose of 75 mg/kg followed by a continuous infusion of 300 mg/kg/24 h were the minimal requirements to achieve the therapeutic targets for piperacillin (60% f T >MIC >16 mg/L).. Standard intermittent dosing regimens do not ensure optimal piperacillin/tazobactam exposure in critically ill patients, thereby risking treatment failure. The use of a loading dose followed by a continuous infusion is recommended for treatment of severe infections in children >2 months of age.

Topics: Adolescent; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Critical Illness; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Infant; Infusions, Intravenous; Male; Microbial Sensitivity Tests; Monte Carlo Method; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Tazobactam

Topics: Aged; Anti-Bacterial Agents; Bacterial Infections; Creatinine; Febrile Neutropenia; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Monte Carlo Method; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

We report a significantly higher occurrence of adverse events associated with prolonged courses of piperacillin-tazobactam compared with other antibacterial agents used for pediatric outpatient parenteral antimicrobial therapy. These adverse events were characterized by a constellation of clinical findings including fever, hematologic abnormalities and transaminitis. Adverse events related to piperacillin-tazobactam should be considered in patients who develop a febrile illness associated with a prolonged course of therapy.

Topics: Adolescent; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Female; Humans; Infant; Infusions, Parenteral; Kaplan-Meier Estimate; Male; Outpatients; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

To study the distribution characteristics and drug resistance of non-fermenting bacterial infection in intensive care unit (ICU) at a tertiary hospital during seven consecutive years, and to provide evidence for rational use of antibiotics in ICU.. A retrospective analysis was conducted. The related data about non-fermentative bacteria obtained from clinical specimens, collected from lower respiratory tract, blood, urine, bile and other secretions of ICU patients admitted to Binzhou Medical University Hospital from January 2009 to December 2015 were retrospectively analyzed. The distribution characteristics and drug resistance of non-fermentative bacteria, and isolation rate of multiple drug resistance (MDR) strains were analyzed.. 2 672 strains of nonfermentative bacteria were isolated during seven consecutive years, accounting for 57.9％ gram negative (G-) bacilli (2 672/4 613),and 35.2％ of all bacteria (2 672/7 587).The top five were Acinetobacter baumannii (38.4％),Pseudomonas aeruginosa (34.6％),Onion burkholderia cepacia (9.9％),Stenotrophomonas maltophilia (6.2％),and Pseudomonas fluorescens (5.6％).Non-fermentative bacteria were mainly isolated from the lower respiratory tract (60.9％).Isolation of the non-fermentative bacteria accounted for over 50％ of G-bacilli during seven consecutive years, and the isolation rate of the top five types of bacteria showed no obvious change, while positive rate of Acinetobacter baumannii showed a tendency to increase (obviously from 26.5％ in 2009 to 50.2％ in 2015),and a lowering trend of positive rate of Onion burkholderia cepacia,Stenotrophomonas maltophilia, and Pseudomonas fluorescens was obvious (from 15.6％,10.6％,13.0％ in 2009 to 5.6％,7.4％,1.4％ in 2015 respectively) was observed. The isolation rate of Pseudomonas aeruginosa was stable (about 30％) during seven consecutive years. The drug susceptibility results showed that the resistant rates of Acinetobacter baumannii against imipenem, meropenem, aminoglycosides and third-generation cephalmsporins were all higher than 70％,while its resistant rate to cefoperazone-sulbactam was relatively lower (40.2％-68.1％)with relatively higher sensitivity rate (23.6％-46.0％).In contrast, the resistant rates of Pseudomonas aeruginosa against antibiotics were low,while the sensitivity rate to fourth-generation cephalmsporins cefepime (58.3％-87.7％)and third-generation cephalmsporins was high (ceftazidime:55.6％-79.3％,piperacillin-tazobactam:62.5％-86.2％,cefoperazone-sulbactam:46.0％-89.8％).From 2009 to 2015,the incidence of MDR strains of Acinetobacter baumannii showed an obvious increasing tendency (from 68.0％ to 84.1％);in contrast, the incidence of MDR strains of Pseudomonas aeruginosa did not show an obviously increase in incidence from 2009 to 2012,on the other hand, it showed a decreasing tendency from a peak 68.6％ in 2012 to 23.5％ in 2015.. The isolation rate of non-fermentative bacteria was high and the drug resistance situation was serious. Therefore,it is important to grasp the knowledge regarding distribution characteristics, drug resistance and variation of non-fermentative bacteria in ICU. It is not only beneficial for both rational use of antibiotics, improve efficacy but also helpful in reducing the emergence of drug resistance stains.

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Bacterial Infections; Cefepime; Cefoperazone; Cephalosporins; Cross Infection; Drug Resistance; Drug Resistance, Bacterial; Gram-Negative Bacteria; Humans; Imipenem; Intensive Care Units; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Retrospective Studies; Thienamycins

Vancomycin and piperacillin-tazobactam are commonly used first guns in the empiric management of critically ill patients. Current studies suggest an increased prevalence of acute kidney injury with concomitant use, however, these studies are few and limited by small sample size. The purpose of this study was to compare the prevalence of nephrotoxicity after treatment with vancomycin alone and concomitant vancomycin and piperacillin-tazobactam treatment at our institution.. Concomitant vancomycin and piperacillin-tazobactam-treated patients will experience greater prevalence of nephrotoxicity compared with vancomycin-only treated patients.. This was a retrospective cohort of patients treated with vancomycin for gram-positive or mixed infections in our facility from 2005 to 2009 who were not receiving hemodialysis at the time of admission. Included patients were stratified by treatment with vancomycin, vancomycin/piperacillin-tazobactam, or vancomycin/an alternative gram-negative rod (GNR) antibiotic. p values for categorical variables were computed using χ(2) while continuous variables were computed using Kruskal-Wallis. Variables deemed statistically significant (< 0.05) were included in the multivariable, log-binomial regression model. Relative risk (RR) and 95% confidence intervals (CI), and p values were computed using a generalized estimating equation (GEE) approach with robust standard errors (i.e., Huber White "sandwich variance" estimates) to accommodate a correlated data structure corresponding to multiple episodes of infection per individual.. A total of 530 patients with 1,007 episodes of infection, were treated with vancomycin (150 patients/302 episodes of infection), vancomycin/piperacillin-tazobactam (213 patients/372 episodes of infection), or vancomycin/GNR alternative (167 patients/333 episodes of infection). Patient demographics, comorbidities, sites of infection, and organisms of infection were compared among groups. After adjusting for statistically significant variables, neither vancomycin/piperacillin-tazobactam (RR = 1.1, 95% CI = 0.99-1.2; p = 0.073) nor vancomycin/GNR alternative (RR = 1.1, 95% CI = 0.98-1.2; p = 0.097) were found to be associated with an increased risk for nephrotoxicity compared with vancomycin alone.. A difference in nephrotoxicity was not observed between vancomycin and vancomycin/piperacillin-tazobactam-treated patients at our institution. Concomitant use as empiric therapy is appropriate, although larger sample sizes are needed to analyze closely this relation among at-risk subsets of this population.

Topics: Adult; Aged; Aged, 80 and over; Animals; Anti-Bacterial Agents; Bacterial Infections; Critical Illness; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Renal Insufficiency; Retrospective Studies; Risk Assessment; Vancomycin

Infection is the most common cause of death in severe AKI, but many patients receiving continuous RRT do not reach target antibiotic concentrations in plasma. Extended infusion of β-lactams is associated with improved target attainment in critically ill patients; thus, we hypothesized that extended infusion piperacillin-tazobactam would improve piperacillin target attainment compared with short infusion in patients receiving continuous RRT.. We conducted an institutional review board-approved observational cohort study of piperacillin-tazobactam pharmacokinetics and pharmacodynamics in critically ill patients receiving continuous venovenous hemodialysis and hemodiafiltration at three tertiary care hospitals between 2007 and 2015. Antibiotic concentrations in blood and/or dialysate samples were measured by liquid chromatography, and one- and two-compartment pharmacokinetic models were fitted to the data using nonlinear mixed effects regression. Target attainment for piperacillin was defined as achieving four times the minimum inhibitory concentration of 16 μg/ml for >50% of the dosing cycle. The probabilities of target attainment for a range of doses, frequencies, and infusion durations were estimated using a Monte Carlo simulation method. Target attainment was also examined as a function of patient weight and continuous RRT effluent rate.. Sixty-eight participants had data for analysis. Regardless of infusion duration, 6 g/d piperacillin was associated with ≤45% target attainment, whereas 12 g/d was associated with ≥95% target attainment. For 8 and 9 g/d, target attainment ranged between 68% and 85%. The probability of target attainment was lower at higher effluent rates and patient weights. For all doses, frequencies, patient weights, and continuous RRT effluent rates, extended infusion was associated with higher probability of target attainment compared with short infusion.. Extended infusions of piperacillin-tazobactam are associated with greater probability of target attainment in patients receiving continuous RRT.

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Critical Illness; Dialysis Solutions; Female; Hemodiafiltration; Humans; Infusions, Intravenous; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Time Factors

To analyze the clinical characteristics of continuous ambulatory peritoneal dialysis (CAPD) associated peritonitis in the tertiary hospitals and to discuss the preventive and therapeutic strategy.
 Methods: The clinical characteristics, pathogens, resistance and outcomes of 126 CAPD associated peritonitis in 104 patients from Jan, 2013 to June, 2016, were retrospectively analyzed.
 Results: Among the patients, the incidence rates of abdominal pain, fever, diarrhea and emesis were 104 (82.54%), 56 (44.44%), 49 (38.89%), and 31 (23.60%), respectively. Among them, 88 patients suffered peritonitis once, other 16 patients suffered multiple peritonitis or recurrent peritonitis for 38 times. Among the 38 times, the numbers for recurrent, repeated or catheter-associated peritonitis were 2, 2, or 3, respectively. Peritoneal fluids from 103 cases were cultured, and 64 cases were positive in bacteria, with a rate of 62.14%. A total of 70 strains of bacteria were separated, including 42 strains of gram-positive bacteria, 21 strains of gram-negative bacteria, and 7 strains of fungus. The most common gram-positive pathogens were Staphylococcus epidermidis, Enterococcus faecalis and Staphylococcus haemolyticus, while Escherichia coli, Klebsiella pneumoniae and Klebsiella pneumoniae were the most common gram-negative bacteria. Candida albicans was the major fungal pathogens. Gram-positive cocci showed resistance to gentamycin, levofloxacin, moxifloxacin, vancomycin and linezolid, with a rate at 20.00%, 36.11%, 5%, 0%, and 0%, respectively. The gram-negative bacilli were resistent to cefoperazone/sulbactam, gentamycin, cephazolin, and ceftazidime, with a rate at 6.25%, 10.53%, 64.29%, and 15.38%, respectively. There were no imipenem, amikacin, piperacillin/tazobactam-resistant strains were found.
 Conclusion: The most common pathogen causing CAPD associated peritonitis is gram-positive bacteria. It is crucial to take the anti-infection therapy for CAPD associated peritonitis early. The positive rates for bacterial culture need to be enhanced through improvement of methods. At the same time, doctors could improve the outcome of CAPD associated peritonitis by adjusting the medication according to the drug sensitivity results.. 目的：探讨某三甲医院持续性非卧床腹膜透析(continuous ambulatory peritoneal dialysis，CAPD)相关性腹膜炎临床特点、致病菌分布及耐药性情况，为临床防治CAPD相关性腹膜炎总结经验。方法：回顾性调查该院2013年1月至2016年6月42个月中，104人126例次CAPD相关性腹膜炎患者的临床特点、致病菌分布、耐药性等情况。
结果：在126例次CAPD相关性腹膜炎中，患者出现腹痛104例次(82.54%)，发热56例次(44.44%)，腹泻49例次(38.89%)，呕吐31例次(23.60%)。126例次CAPD相关性腹膜炎中，发生一次腹膜炎的88人次，多次和反复发作的腹膜炎16人38例次，其中复发性腹膜炎2例，腹膜炎重现2例，导管相关性腹膜炎3例。在103例送检的腹水标本中，培养阳性64例次，阳性率达62.14%。共分离出致病菌70株，其中革兰阳性细菌42株，革兰阴性细菌21株，真菌7株。主要的革兰阳性菌包括表皮葡萄球菌、粪肠球菌、溶血葡萄球菌；主要的革兰阴性菌包括大肠埃希菌、肺炎克雷伯菌、铜绿假单胞菌；真菌以白假丝酵母菌为主。革兰阳性菌对庆大霉素、左氧氟沙星、莫西沙星、万古霉素、利奈唑胺的耐药率分别为20.00%，36.11%，5.00%，0%，0%；革兰阴性菌对头孢哌酮/舒巴坦、庆大霉素、头孢唑啉、头孢他啶的耐药率分别为6.25%，10.53%，64.29%，15.38%，对亚胺培南、阿米卡星、哌拉西林/他唑巴坦的耐药率均为0%。结论：革兰阳性菌是CAPD相关性腹膜炎的主要致病菌，临床不仅应尽早开始经验性治疗，而且要考虑如何通过改善培养方法以提高阳性检出率；可以根据药敏结果调整用药，以促进患者CAPD相关性腹膜炎的治愈和腹膜功能的恢复。.

Topics: Abdominal Pain; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Candidiasis; Catheters; Diarrhea; Drug Resistance, Bacterial; Enterococcus faecalis; Escherichia coli; Fever; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Imipenem; Klebsiella pneumoniae; Microbial Sensitivity Tests; Mycoses; Penicillanic Acid; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Piperacillin; Piperacillin, Tazobactam Drug Combination; Recurrence; Retrospective Studies; Staphylococcus epidermidis; Staphylococcus haemolyticus; Vomiting

Topics: Acinetobacter; Amikacin; Anti-Bacterial Agents; Antifungal Agents; Bacterial Infections; Cancer Care Facilities; Carbapenems; Ceftazidime; Ciprofloxacin; Clindamycin; Disk Diffusion Antimicrobial Tests; Drug Resistance, Bacterial; Enterobacteriaceae; Feces; Fluconazole; Gentamicins; Humans; India; Methicillin-Resistant Staphylococcus aureus; Mycoses; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas; Yeasts

Piperacillin/tazobactam is a frequently prescribed antibiotic in pediatric intensive care units, but pharmacokinetic data to justify the optimal piperacillin/tazobactam dosing regimen are sparse in critically ill children.. Blood samples (2-4 per child) were collected from 13 children ages 9 months to 6 years admitted to the pediatric intensive care unit who were receiving standard piperacillin/tazobactam dosing regimens to treat infections. Piperacillin concentrations were measured by a bioassay, and the population pharmacokinetics of the piperacillin component was conducted using nonparametric adaptive grid (BigNPAG) with adaptive γ. Multiple models were tested to determine the best fit of the data. A 5000 patient Monte Carlo simulation was performed to determine the probability of target attainment (PTA) for piperacillin/tazobactam 50 mg/kg (of the piperacillin component) every 4 hours, 80 mg/kg every 8 hours and 100 mg/kg every 6 hours as 0.5-, 3- or 4-hour infusions in a population of 1- to 6-year-old male children. Centers for Disease Control and Prevention weight for age charts were used as weight distributions. The percent of the dosing interval of the free drug is above the minimum inhibitory concentration (MIC) (fT>MIC) was calculated over a range of MICs from 0.03 to 128 μg/mL. The bactericidal target attainment was defined as ≥50% fT>MIC for piperacillin/tazobactam. PTA ≥90% at each MIC was defined as optimal.. A 2 compartment model fitted piperacillin concentration data the best. Mean (standard deviation) population estimates for clearance, volume of the central compartment (Vc) and intercompartment transfer constants were 0.299 (0.128) L/hr/kg, 0.249 (0.211) L/kg, 6.663 (6.871) hours(-1) and 8.48 (7.74) hours(-1), respectively. This resulted in a mean (standard deviation) elimination half-life of 1.39 (0.62) hours. The bias, precision and r² for the individual predicted versus observed concentrations were -0.055, 0.96 μg/mL and 0.999, respectively. The only dosing regimens that achieved optimal PTA at the Clinical Laboratory Standards Institute susceptibility breakpoint of 16 μg/mL against Psuedomonas aeruginosa were 100 mg/kg every 6 hours administered as a 3-hour prolonged infusion and 400 mg/kg administered as a 24-hour continuous infusion. These dosing regimens also achieved 77.7% and 74.8% PTA, respectively, at a MIC of 32 μg/mL.. These are the first pharmacokinetic data of piperacillin/tazobactam (piperacillin component) in critically ill pediatric patients (1-6 years of age). Based on these data, 100 mg/kg q6h as a 3-hour infusion and 400 mg/kg continuous infusion were the only regimens to provide optimal PTA at the Clinical Laboratory Standards Institute breakpoint of 16 μg/mL.

Topics: Bacterial Infections; Child; Child, Preschool; Cohort Studies; Critical Illness; Female; Humans; Infant; Intensive Care Units, Pediatric; Male; Monte Carlo Method; Penicillanic Acid; Philadelphia; Piperacillin; Piperacillin, Tazobactam Drug Combination

Immunosuppressive patients are at risk of fungal and bacterial infections. Therefore, these patients receive prophylactic, preemptive, empirical or target antifungal and concomitant antibiotic therapy. To this end, caspofungin (CAS) or voriconazole (VRC) antifungals and cefoperazone-sulbactam (CPZ/SAM) or piperacillin-tazobactam (PIP/TAZ) antibiotics may be used. Here, we aimed to investigate the interaction between these antifungals and antibiotics by in vitro and in vivo methods. The interaction was tested by chequerboard analysis and fractional inhibitory concentration index (FICI). It was also tested in a neutropenic mice-invasive candidiasis model and evaluated by fungal burden in kidney tissue of infected animals from the first day to the fifth day of treatment with 24 h intervals. A synergism was detected between CAS and CPZ/SAM (FICI = 0.1) and PIP/TAZ (FICI = 0.3). Fungal burden in tissues of drug-treated mice was reduced compared with controls in a time-dependent manner. In comparison with CAS-alone treated group, there were 1.32 log10 reductions of fungal burden in CAS + CPZ/SAM (p = 0.002) and in CAS + PIP/TAZ group (p = 0.14). The same interactions were not found with VRC and antibiotics. CPZ/SAM had stronger synergistic interaction with CAS than PIP/TAZ. The mechanism of synergism is not well understood. This is most likely due to an increase in the anticandidal effect of CAS plus antibiotics.

Topics: Animals; Anti-Bacterial Agents; Antifungal Agents; Bacterial Infections; Candida albicans; Candidiasis; Caspofungin; Cefoperazone; Drug Interactions; Echinocandins; Female; Lipopeptides; Mice; Mice, Inbred BALB C; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pyrimidines; Sulbactam; Triazoles; Voriconazole

Piperacillin in combination with tazobactam, a β-lactamase inhibitor, is a commonly used intravenous antibiotic for the empirical treatment of infection in intensive care patients, including burn patients. The purpose of this study was to develop a population pharmacokinetic (PK) model for piperacillin in burn patients and to predict the probability of target attainment (PTA) using MICs and concentrations simulated from the PK model. Fifty burn patients treated with piperacillin-tazobactam were enrolled. Piperacillin-tazobactam was administered via infusion for approximately 30 min at a dose of 4.5 g (4 g piperacillin and 0.5 g tazobactam) every 8 h. Blood samples were collected just prior to and at 1, 2, 3, 4, and 6 h after the end of the infusion at steady state. The population PK model of piperacillin was developed using NONMEM. A two-compartment first-order elimination PK model was finally chosen. The covariates included were creatinine clearance (CLCR), day after burn injury (DAI), and sepsis. The final PK parameters were clearance (liters/h) (equal to 16.6 × [CLCR/132] + DAI × [-0.0874]), central volume (liters) (equal to 25.3 + 14.8 × sepsis [0 for the absence or 1 for the presence of sepsis]), peripheral volume (liters) (equal to 16.1), and intercompartmental clearance (liters/h) (equal to 0.636). The clearance and volume of piperacillin were higher than those reported in patients without burns, and the terminal half-life and PTA decreased with the increased CLCR. Our PK model suggests that higher daily doses or longer durations of infusion of piperacillin should be considered, especially for burn patients with a CLCR of ≥ 160 ml/min.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Burns; Computer Simulation; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Models, Statistical; Monte Carlo Method; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Young Adult

Piperacillin-tazobactam is frequently used for empirical and targeted therapy of infections in critically ill patients. Considerable pharmacokinetic (PK) variability is observed in critically ill patients. By estimating an individual's PK, dosage optimization Bayesian estimation techniques can be used to calculate the appropriate piperacillin regimen to achieve desired drug exposure targets. The aim of this study was to establish a population PK model for piperacillin in critically ill patients and then analyze the performance of the model in the dose optimization software program BestDose. Linear, with estimated creatinine clearance and weight as covariates, Michaelis-Menten (MM) and parallel linear/MM structural models were fitted to the data from 146 critically ill patients with nosocomial infection. Piperacillin concentrations measured in the first dosing interval, from each of 8 additional individuals, combined with the population model were embedded into the dose optimization software. The impact of the number of observations was assessed. Precision was assessed by (i) the predicted piperacillin dosage and by (ii) linear regression of the observed-versus-predicted piperacillin concentrations from the second 24 h of treatment. We found that a linear clearance model with creatinine clearance and weight as covariates for drug clearance and volume of distribution, respectively, best described the observed data. When there were at least two observed piperacillin concentrations, the dose optimization software predicted a mean piperacillin dosage of 4.02 g in the 8 patients administered piperacillin doses of 4.00 g. Linear regression of the observed-versus-predicted piperacillin concentrations for 8 individuals after 24 h of piperacillin dosing demonstrated an r(2) of >0.89. In conclusion, for most critically ill patients, individualized piperacillin regimens delivering a target serum piperacillin concentration is achievable. Further validation of the dosage optimization software in a clinical trial is required.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Bayes Theorem; Creatinine; Critical Illness; Drug Dosage Calculations; Drug Therapy, Computer-Assisted; Female; Humans; Male; Metabolic Clearance Rate; Microbial Sensitivity Tests; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Precision Medicine; Pseudomonas aeruginosa; Young Adult

It has been reported in many studies that one of the main factors influencing morbidity and mortality in patients receiving transplants is infection after transplantation.. The study included 190 adult patients undergoing orthotopic liver transplantation (OLT) between September 2001 and December 2007. All the patients were followed prospectively for infections from the OLT date and during the first 4 weeks after surgery. Immunosuppression consisted of steroids and tacrolimus. Antimicrobial prophylaxis included piperacillin/tazobactam, fluconazole, and selective bowel decontamination (SBD) was performed. Samples of clinical materials were investigated for microbiological cultures. The micro-organisms were cultured and identified in accordance with standard bacteriological procedures. Susceptibility testing was performed using Clinical and Laboratory Standards Institute procedures.. From 190 OLT recipients, 2213 clinical samples were obtained for microbiological examination. Positive cultures were found in 27.2% (n = 603) of all samples tested; 1252 strains were collected. Gram-positive bacteria were found in 64.1% (n = 802), Gram-negative bacteria were found in 31.6% (n = 396), and fungal strains were isolated in 4.3% (n = 54). Surgical site specimens (n = 1031) were obtained from 190 recipients during the first month after transplantation. Positive cultures accounted for 29.2% (n = 301) of all samples tested. Among the isolated microbial strains (n = 677), most common were Gram-positive bacteria (73.7%; n = 499). Gram-negative bacteria comprised 25.1% (n = 170). There were fungal strains in 1.2% (n = 8). There were 539 urine specimens. Positive cultures accounted for 16.7% (n = 90) of those. Among the isolated microbial strains (n = 210), most common were Gram-negative bacteria (62.4%; n = 131). Gram-positive bacteria comprised 28.6% (n = 60) and fungi 9% (n = 19). There were 549 blood specimens. Positive cultures were found in 30.6% (n = 168) of all samples tested. Among the isolated microbial strains (n = 263), most common were Gram-positive bacteria in 72.3% (n = 190); Gram-negative bacteria were found in 26.2% (n = 69), and fungal strains were isolated in 1.5% (n = 4). There were 69 respiratory tract specimens. Positive cultures were found in 46.4% (n = 32) of all samples tested. Among the isolated microbial strains (n = 84), most common were Gram-positive bacteria (51.2%; n = 43); Gram-negative bacteria comprised 27.4% (n = 23) and fungi 21.4% (n = 18).. (1) Surgical site samples were predominated samples after LTx. (2) Our study showed Gram-positive bacteria were 64.1% (n = 802), Gram-negative bacteria, 31.6% (n = 396) and fungal strains isolated in 4.3% (n = 54). (3) The increased proportion of isolates of multi-drug-resistant bacterial strains (methicillin resistant coagulase negative Staphylococcus, vancomycin-resistant Enterococcus, high-level aminoglycoside resistance, and extended- spectrum β-lactamase). (4) These data indicate strict cooperation infection control procedures in these patients.

Topics: Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Antifungal Agents; Bacterial Infections; Female; Fluconazole; Fungi; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Intestines; Liver Transplantation; Male; Middle Aged; Mycoses; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Postoperative Complications; Prospective Studies

Topics: Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Colistin; Humans; Infant; Infant, Newborn; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Public Health Administration; Virus Diseases

The physical compatibility of vancomycin and piperacillin sodium-tazobactam at dosing concentrations commonly administered during prolonged infusions was studied.. Concentrations of vancomycin and piperacillin sodium-tazobactam typically used in prolonged infusions were evaluated. Vancomycin hydrochloride and piperacillin sodium-tazobactam were reconstituted with 0.9% sodium chloride injection and diluted to the following concentrations: vancomycin, 4 mg/mL; piperacillin sodium 30 mg/mL plus tazobactam 3.75 mg/mL; and piperacillin sodium 40 mg/mL plus tazobactam 5 mg/mL. Combinations of vancomycin and piperacillin sodium-tazobactam were tested using simulated Y-site administration; phenytoin served as a positive control for precipitation with vancomycin. Each combination was prepared in triplicate, alternating the order of drug addition, and stored without light protection at room temperature. The resultant admixtures were microscopically observed and subjected to particle-size and turbidity analyses for five days. Statistical analyses were performed using two-way repeated measures analysis of variance with conservative Bonferroni corrections for multiple comparisons.. Vancomycin was compatible with piperacillin sodium-tazobactam in the concentrations tested. No particulate matter was observed by the unaided eye. Similarly, the antibiotic admixtures displayed no differences microscopically, by particle-size analysis, or by turbidity analysis when compared with negative controls at five days.. Vancomycin 4 mg/mL and piperacillin sodium 30 mg/mL plus tazobactam 3.75 mg/mL or piperacillin sodium 40 mg/mL plus tazobactam 5 mg/mL were physically compatible during simulated Y-site injection at room temperature without light protection for five days.

Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Administration Schedule; Drug Combinations; Drug Stability; Humans; Infusions, Intravenous; Isotonic Solutions; Nephelometry and Turbidimetry; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Time Factors; Vancomycin

Appendicitis is a frequent clinical condition in normal children that may be complicated by community-acquired secondary peritonitis (CASP). We evaluated the potential efficacy of different drugs for initial treatment of this condition, as recommended by recent Consensus Conference and Guidelines for paediatric patients. Susceptibility to ampicillin-sulbactam, ertapenem, gentamycin, piperacillin, piperacillin-tazobactam, vancomycin, and teicoplanin was evaluated according to EUCST 2012 recommendations in aerobic bacteria isolated from peritoneal fluid in CASP diagnosed from 2005 to 2011 at 'Istituto Giannina Gaslini', Genoa, Italy. A total of 114 strains were analysed: 83 E. coli, 15 P. aeruginosa, 6 Enterococci, and 10 other Gram-negatives. Resistance to ampicillin-sulbactam was detected in 37% of strains, while ertapenem showed a potential resistance of 13% (all P. aeruginosa strains). However, the combination of these drugs with gentamicin would have been increased the efficacy of the treatment to 99 and 100%, respectively. Resistance to piperacillin-tazobactam was 3%, while no strain was resistant to meropenem. Our data suggest that monotherapy with ampicillin-sulbactam or ertapenem for community-acquired secondary peritonitis would present a non-negligible rate of failure, but the addition of gentamycin to these drugs could reset to zero this risk. On the contrary, monotherapy with piperacillin-tazobactam or meropenem is highly effective.

Topics: Ampicillin; Anti-Bacterial Agents; Bacterial Infections; beta-Lactams; Child; Community-Acquired Infections; Drug Resistance, Bacterial; Drug Therapy, Combination; Ertapenem; Gentamicins; Hospitals, Pediatric; Humans; Italy; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Peritonitis; Piperacillin; Piperacillin, Tazobactam Drug Combination; Practice Guidelines as Topic; Sulbactam; Thienamycins

Severe sepsis and septic shock can alter the pharmacokinetics of broad-spectrum β-lactams (meropenem, ceftazidime/cefepime, and piperacillin-tazobactam), resulting in inappropriate serum concentrations. Obesity may further modify the pharmacokinetics of these agents. We reviewed our data on critically ill obese patients (body mass index of ≥ 30 kg/m(2)) treated with a broad-spectrum β-lactam in whom therapeutic drug monitoring was performed and compared the data to those obtained in critically nonobese patients (body mass index of <25 kg/m(2)) to assess whether there were differences in reaching optimal drug concentrations for the treatment of nosocomial infections. Sixty-eight serum levels were obtained from 49 obese patients. There was considerable variability in β-lactam serum concentrations (coefficient of variation of 50% to 92% for the three drugs). Standard drug regimens of β-lactams resulted in insufficient serum concentrations in 32% of the patients and overdosed concentrations in 25%. Continuous renal replacement therapy was identified by multivariable analysis as a risk factor for overdosage and a protective factor for insufficient β-lactam serum concentrations. The serum drug levels from the obese cohort were well matched for age, gender, renal function, and sequential organ failure assessment (SOFA) score to 68 serum levels measured in 59 nonobese patients. The only difference observed between the two cohorts was in the subgroup of patients treated with meropenem and who were not receiving continuous renal replacement therapy: serum concentrations were lower in the obese cohort. No differences were observed in pharmacokinetic variables between the two groups. Routine therapeutic drug monitoring of β-lactams should be continued in obese critically ill patients.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; beta-Lactams; Case-Control Studies; Cefepime; Ceftazidime; Cephalosporins; Drug Monitoring; Enzyme Inhibitors; Female; Humans; Male; Meropenem; Middle Aged; Obesity; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Renal Replacement Therapy; Sepsis; Shock, Septic; Tazobactam; Thienamycins; Young Adult

Radical cystectomy is associated with the highest morbidity and mortality of all commonly performed urological cancer treatment procedures. Postoperative infection remains a major problem. We herein report the results of an open prospective study involving radical cystectomies, undertaken to evaluate the efficacy of 0.5/2 g tazobactam-piperacillin (TAZ-PIPC) in the prevention of postoperative infectious complications. Antimicrobial prophylaxis was performed using 0.5/2 g TAZ-PIPC (2.5 g i.v.) every 3 h during surgery and then twice a day for 3 days postoperatively. The patients were monitored to detect any postoperative infections. During surgery, irrigation fluid from the total abdominal cavity was taken for bacterial culture just before closing the abdomen. Surveillance cultures of drain discharge and urine from ureteral stents were also performed. Other samples were taken for bacterial culture when an infection was suspected. The total postoperative bacterial infection rate was 20.0% (7/35), and surgical site infection rate was 5.7% (2/35). These rates are lower than those documented in other studies. This study, even though open and noncomparative, showed that a short-interval regimen containing 0.5/2 g TAZ-PIPC provides adequate antimicrobial prophylaxis in patients undergoing radical cystectomy.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacteria; Bacterial Infections; Cystectomy; Female; Humans; Japan; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Surgical Wound Infection; Treatment Outcome; Urinary Tract Infections

Topics: Adult; Anti-Bacterial Agents; Bacterial Infections; Chromatography, High Pressure Liquid; Drug Monitoring; Humans; Male; Obesity; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Serum

India has the largest diabetic population of 50.8 million that could reach an epidemic proportion by 2030. Diabetic foot infection is one of the dreaded complications of diabetes.  Only a few studies that focus on patterns of diabetic foot infection in our region, where diabetic foot care is inadequate, are available. This study evaluated microbial and clinical characteristics of diabetic foot infections that will be helpful in taking appropriate measures for their management.. In this prospective study conducted during 2008-2009, sixty-two diabetic foot patients underwent detailed history, clinical examination, and laboratory investigations including parameters of systemic infections. Microbial culture and sensitivity were performed at the time of presentation.. Among 62 cases, 43.5% had mono-microbial infection, 35.5% had poly-microbial infections, and 21% had sterile culture. Among 82 bacteria isolated, 68% were Gram negative and 32% were Gram positive. Leukocyte counts were higher (16928±9642 versus 14593±6687 cells/mm(3)) and haemoglobin (7.9±2.4 versus 9.2±2.2 mg/dl) lower in poly-microbial compared to mono-microbial infections. Haemoglobin counts were lower and leukocyte counts higher in Gram-negative compared to Gram-positive infections. Patients with sterile cultures also had clinical evidence of persistent infection. Escherichia coli were the most common isolate and piperacillin/tazobactam showed highest sensitivity.. Gram-negative bacteria were most prevalent in diabetic foot infection. It is not uncommon to have culture reports negative despite clinical evidence of infection. This study suggests that piperacillin/tazobactam should be the treatment of choice on an empirical basis prior to a definitive bacteriological study and in cases with negative culture reports.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Diabetic Foot; Female; Humans; India; Male; Microbial Sensitivity Tests; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prevalence; Prospective Studies

Surveys of bacterial infections among neutropenic cancer patients frequently report pooled antibiotic susceptibility data. Management guidelines address initial antibiotic regimens for febrile neutropenia. In this study, rates of bacterial infection and antibiotic susceptibilities among initial and subsequent or breakthrough episodes of fever were analysed. Prospective surveillance of fever of unknown origin (FUO), clinically documented infection and microbiologically documented infection (MDI) was conducted in the haemato-oncology and haematopoietic stem cell transplantation wards in a single cancer centre in Israel. Subsequent infections were defined as those developing during or after broad-spectrum antibiotic treatment. A total of 567 febrile episodes were documented among 271 patients. Bacterial MDIs were documented in 104/162 (64%) initial febrile episodes and 75/405 (19%) subsequent episodes and Gram-negative bacteria predominated (64% and 71%, respectively). Escherichia coli was the most common species isolated. Higher antibiotic susceptibilities were observed for initial compared with subsequent MDIs for Gram-negative bacteria [ceftazidime 80% vs. 45%, piperacillin/tazobactam (TZP) 86% vs. 40% and meropenem 95% vs.76%] and Gram-positive bacteria. TZP monotherapy was the most commonly used antibiotic and its susceptibility decreased to 22.2% following its use. Appropriate empirical antibiotic treatment was administered in 71/97 (73%) initial and 40/74 (54%) subsequent episodes (P=0.009) and was significantly associated with mortality (adjusted odds ratio=0.4, 95% confidence interval 0.18-0.87). We conclude that previous antibiotic exposure significantly impacts antibiotic susceptibility and that pooled reporting of all infections can be misleading. Treatment guidelines should address the antibiotic treatment of breakthrough fever.

Topics: Adult; Aged; Aged, 80 and over; Bacteremia; Bacterial Infections; Ceftazidime; Drug Resistance, Bacterial; Escherichia coli; Fever; Gram-Positive Bacteria; Hematologic Diseases; Hematopoietic Stem Cell Transplantation; Hospitalization; Humans; Israel; Meropenem; Middle Aged; Odds Ratio; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Thienamycins; Treatment Outcome; Young Adult

A 10-year-old boy with acquired, very severe aplastic anemia developed acute lung injury after the administration of equine antithymocyte globulin, during conditioning for allogenic bone marrow transplantation. Limited cases of antithymocyte globulin-induced acute lung injury have been described in adults. The respiratory worsening was sudden and required mechanical ventilation. The clinical course was complicated by sepsis with Escherichia coli, vancomycin-resistant enterococci, and Stenotrophomonas maltophilia. Implications for treatment are discussed and earlier literature is reviewed.

Topics: Acute Lung Injury; Anemia, Aplastic; Animals; Anti-Bacterial Agents; Antilymphocyte Serum; Bacterial Infections; Bone Marrow Transplantation; Child; Cyclophosphamide; Horses; Humans; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis; Transplantation Conditioning; Vancomycin; Vidarabine

Increased antibacterial use is associated with a greater likelihood of reduced effectiveness as a result of resistance development in the future. The objective of this study was to evaluate the cost effectiveness of ertapenem versus piperacillin/tazobactam in the treatment of diabetic foot infections (DFIs) from the UK NHS perspective, accounting for the development of antibacterial resistance over time.. A decision-tree model was developed to estimate the cost effectiveness of ertapenem versus piperacillin/tazobactam at different timepoints in the 36 months following introduction of treatment. Development of antibacterial resistance was incorporated in the analysis using a previously published compartment (susceptible-infected-susceptible) model. The development of resistance was a function of the clearance rate of pathogens and the size of the proportion of the population prescribed the antibacterial. The microbiological clearance rate and clinical success rates were assumed to be related and were obtained from the SIDESTEP study. These data included resistant pathogens (either acquired or intrinsic resistance) such as Enterobacteriaceae, meticillin-resistant Staphylococcus aureus, enterococci and Pseudomonas aeruginosa. Model outcomes over time included lifetime QALYs, direct medical costs (year 2006 values) and cost per QALY saved. Clinical efficacy of second-line treatment, direct medical costs and utilities were derived from other existing studies. Probabilistic sensitivity analyses were undertaken to estimate the uncertainty of model outcomes. Costs and QALYs were discounted at 3.5% per annum.. The model suggested savings of pound407 (95% uncertainty interval [UI] -337, 1501) per patient when DFIs were treated with ertapenem instead of piperacillin/tazobactam after 1 month's treatment. Probabilistic sensitivity analysis suggested a 91% probability of the incremental cost per QALY saved being within a threshold for cost effectiveness of pound20,000. After 3 years it is expected that the antibacterial resistance profile with piperacillin/tazobactam would increase at a greater rate than with ertapenem. As a result, the cost savings with ertapenem are expected to increase to pound3465 (95% UI 2502, 4564), and ertapenem will additionally result in greater clinical success rates and lifetime QALY savings (1.16; 95% UI 0.46, 2.06).. Ertapenem appears to be a cost-saving and possibly an economically dominant therapy over piperacillin/tazobactam for the treatment of patients with DFIs from the UK NHS perspective.

Topics: Anti-Bacterial Agents; Bacterial Infections; beta-Lactams; Cost-Benefit Analysis; Decision Trees; Diabetic Foot; Direct Service Costs; Drug Costs; Drug Resistance, Bacterial; Ertapenem; Humans; Models, Biological; Models, Econometric; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Quality-Adjusted Life Years; Treatment Outcome; United Kingdom

Piperacillin-tazobactam was administered as a single dose (4.5 g intravenous) to five patients with stabilized external pancreatic fistula. The penetration into pancreatic juice was prompt, and inhibitory concentrations were achieved and maintained for different periods (0.5 to 6 h) according to bacterial susceptibility and patients' characteristics. Piperacillin and tazobactam showed superimposable pharmacokinetics in both serum and pancreatic juice.

Topics: Aged; Ampulla of Vater; Anti-Bacterial Agents; Bacterial Infections; beta-Lactamase Inhibitors; Common Bile Duct Neoplasms; Female; Humans; Male; Middle Aged; Pancreatic Diseases; Pancreatic Juice; Pancreatic Neoplasms; Pancreaticoduodenectomy; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

To conduct a multicentre observational study to describe management of foot infections in diabetes in the out-patient setting in Italy.. Ten centres equally distributed nationwide were asked to collect, by means of a spreadsheet (Access/Excel Microsoft program), data concerning 30 consecutive diabetic patients with foot infections deemed suitable for antibiotic treatment in the out-patient setting. Centres with > or = 5 years' experience of out-patient management were selected. Data from 271 consecutive patients treated as out-patients were collected and analysed by the central coordinator. Statistical analysis was performed using the SPSS statistical software package.. Lesions were mainly located at the toes and midfoot (33.6 and 30.2%, respectively); 63 (23.2%) patients had multiple ulcers. Seventy (25.8%) patients also had concomitant osteomyelitis. Three hundred and four pathogens, including Gram-positive and Gram-negative aerobes and anaerobes, were isolated in 219/271 patients (80.8%) by culturing debrided tissue (71.2%) or purulent material (28.8%). Infections were polymicrobial in 33.8% of patients. The most common pathogens were Staphylococcus aureus (27.3%) and Pseudomonas spp. (20.4%); enterobacteriaceae, enterococci, streptococci and anaerobes accounted for 11.5, 7.6, 6.9 and 1.9%, respectively. Antibiotics were frequently administered by parenteral route and frequently in combination. Piperacillin/tazobactam was the parenteral antibiotic most frequently utilized (21.1%). Cure/improvement was observed in 93.4% of patients.. Foot ulcers in diabetes are common and serious; the aetiology is often polymicrobial, often including S. aureus and Pseudomonas spp. Treatment in the out-patient setting is safe and effective, and penicillins together with beta-lactamase inhibitors and fluoroquinolones are the most frequent choice.

Topics: Adult; Aged; Aged, 80 and over; Ambulatory Care; Anti-Bacterial Agents; Bacterial Infections; Diabetic Foot; Female; Humans; Italy; Male; Middle Aged; Outpatient Clinics, Hospital; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas Infections; Staphylococcal Infections; Young Adult

To aid clinicians in selecting the appropriate approach for treating patients with diabetic foot infections, we investigated whether any baseline clinical findings predicted an unfavourable clinical outcome. Using data from a large, prospective treatment trial of diabetic foot infections (SIDESTEP), we assessed the association between clinical treatment failure and baseline history, physical and laboratory findings, by univariate and multivariate logistic regression analyses. Among 402 patients clinically evaluable 10 days after completing antibiotic therapy, baseline factors significantly (P < 0.05) associated by univariate analysis with treatment failure were 'severe' (versus 'moderate') University of Texas (UT) wound grade; elevated white blood cell count, C-reactive protein or erythrocyte sedimentation rate; high wound severity score; inpatient treatment; low serum albumin; male sex; and skin temperature of affected foot >10 degrees C above that of unaffected foot. By multivariate logistic regression only severe UT wound grade (odds ratio 2.1) and elevated white blood cell count [odds ratio 1.7 for a 1 standard deviation (2971 cells/mm(3)) increase] remained statistically significant. Clinical failure rates were 46% for patients with both risk factors compared with 10% for patients with no risk factors and 16-17% for patients with one risk factor. Increased white blood cell count and severe UT wound grade at baseline, but not other features, were significant independent and additive risk factors for clinical failure in patients treated for a diabetic foot infection.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; beta-Lactams; Diabetic Foot; Ertapenem; Female; Humans; Leukocyte Count; Male; Middle Aged; Multivariate Analysis; Outcome Assessment, Health Care; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Randomized Controlled Trials as Topic; Risk Factors; Severity of Illness Index; Treatment Failure

The selection of antimicrobial agents in the 2006 Guidelines (consensus statement) on Empiric Therapy for Complicated Intra-Abdominal Infections (IAIs) in Asia was based on resistance and epidemiological data from the Asian region. In these 2006 guidelines, single agent therapy using the beta-lactam/beta-lactamase inhibitors ampicillin/sulbactam or cefoperazone-sulbactam is recommended for mild-to-moderate cases, while piperacillin-tazobactam is recommended for high-severity cases. When using carbapenems, ertapenem is recommended for mild-to-moderate cases, while imipenem and meropenem are recommended for high-severity cases. For combination regimes, two types of agents are recommended: cephalosporin-based and monobactam-based. For mild-to-moderate cases, a third generation cephalosporin plus metronidazole is recommended. For high-severity cases, a third or fourth generation cephalosporin plus metronidazole+/-amikacin is recommended. For the monobactam-based regimen, aztreonam plus metronidazole is recommended for high-severity cases only.

Topics: Abdomen; Anti-Infective Agents; Asia; Bacterial Infections; beta-Lactamase Inhibitors; Consensus; Drug Resistance, Bacterial; Drug Therapy, Combination; Enterobacteriaceae; Enterobacteriaceae Infections; Fluoroquinolones; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Practice Guidelines as Topic

To evaluate potential cost savings, trial data were used to determine the clinical outcomes for i.v. ertapenem given once daily and i.v. piperacillin-tazobactam given every six hours daily in treating diabetic foot infections.. A cost-minimization analysis (CMA) was conducted on the drug-dosing data of the subset of patients enrolled in a recent double-blind randomized trial who were treated solely as inpatients and were clinically evaluable at fi nal assessment (n = 99). Cost per dose was calculated from (a) average hospital acquisition price per dose for ertapenem ($40.52) or piperacillin-tazobactam ($13.58), (b) average U.S. wages and benefits for labor, based on nine published time-and-motion studies of i.v. antibiotic preparation and administration ($3.10), and (c) consumable supplies, using a 40% discount off the manufacturer list price ($2.90). For each patient, the actual number of antibiotic doses given was multiplied by total cost per dose.. There were no significant differences between antibiotic groups with respect to patient demographics, percentage with a severe wound, and mean days of i.v. therapy. Compared with piperacillin-tazobactam, patients treated with ertapenem received significantly fewer mean doses (25.5 versus 7.5; p < 0.0001) and lower antibiotic-related costs ($502.76 versus $355.55, respectively; p < 0.001). The $147.21 difference between groups accounts for approximately 3% of total hospital Medicare reimbursements for these infections.. A CMA of treatment of diabetic foot infections showed that, compared with piperacillin-tazobactam given four times daily i.v., ertapenem given once daily i.v. was associated with lower drug acquisition and supply costs and less time and labor devoted to preparation and administration of i.v. therapy.

Topics: Anti-Bacterial Agents; Bacterial Infections; beta-Lactams; Diabetic Foot; Drug Administration Schedule; Drug Combinations; Ertapenem; Female; Health Care Costs; Humans; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

Piperacillin-Tazobactam (Pip-Taz) is an evidence-based empirical treatment of febrile neutropenia in adolescents and adults. No data are available in pediatric cancer patients <25 months of age. In this retrospective, multicenter data survey, the analysis focuses on safety, tolerance, and efficacy. The daily dose administered was 240 mg/kg given in three equally divided doses. Data on 156 Pip-Taz treatment courses in 69 children <25 months from five pediatric cancer treatment centers (2001-2005) were analyzed. The median duration of treatment with Pip-Taz was 5 days (range, 1-23 days; 1-12 Pip-Taz courses per patient). Pip-Taz was started on the first day of fever in 90% of all courses, in 6% in the first 72 h, and in 4% as second- or third-line agent. Forty-five percent of all patients were neutropenic. In all patients, the outcome was favorable independent whether Pip-Taz was given as monotherapy (42 courses; 27%) or in combination. Overall, Pip-Taz was well tolerated and discontinued due to adverse events in only two patients who experienced non-life-threatening allergic reactions (skin rash and wheezing). The results of this study are preliminary due to the methodological limitations of a retrospective survey. Taking this bias into consideration, Pip-Taz appears to be a safe, and feasible alternative in pediatric cancer patients with febrile neutropenia <25 months of age suggesting that the inclusion of children of all age groups in future prospective controlled studies evaluating Pip-Taz is justified.

Topics: Bacterial Infections; Fever of Unknown Origin; Humans; Hypersensitivity; Infant; Infant, Newborn; Neoplasms; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Treatment Outcome; Withholding Treatment

We assessed infections caused by extended-spectrum-beta-lactamase-producing Escherichia coli or Klebsiella spp. treated with piperacillin-tazobactam to determine if the susceptibility breakpoint predicts outcome. Treatment was successful in 10 of 11 nonurinary infections from susceptible strains and in 2 of 6 infections with MICs of >16/4 mug/ml. All six urinary infections responded to treatment regardless of susceptibility.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; beta-Lactamase Inhibitors; Escherichia coli; Female; Humans; Klebsiella oxytoca; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Time Factors; Treatment Outcome; Urinary Tract Infections

The association between piperacillin/tazobactam and the positivity of the galactomannan (GM) detection ELISA test is well described. Little information is available about the kinetics of GM in patients treated with piperacillin/tazobactam. The present study aimed at clarifying the baseline interaction between piperacillin/tazobactam and GM in patients receiving this drug.. Seven patients undergoing abdominal surgery received perioperative prophylaxis with piperacillin/tazobactam. Each patient received three doses of 4.5 g of the drug, administered at 8 h intervals (one before and two after surgery). Three patients received antibiotic batches with 'medium' (GM-index = 1.782) and four patients received antibiotic batches with 'high' (GM-index = 6.665) GM content. Serum samples for GM evaluation were collected before drug infusion and at times +1, +3, +6 and +8 h after the first and third infusions.. GM levels increased after infusion, in particular when batches with 'high' GM content were used. Moreover, a non-statistically significant increase between the first dose and the third dose was observed. All samples taken >6 h after administration were negative (GM-index < 0.2), both with the 'medium' and the 'high' GM content batches.. The low content of GM 8 h after piperacillin/tazobactam infusion suggests that in non-neutropenic cancer patients with solid tumours receiving up to three doses of piperacillin/tazobactam, serum sampling for GM detection should be performed immediately before the next piperacillin/tazobactam administration.

Topics: Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacterial Infections; Colon; False Positive Reactions; Female; Galactose; Gastrectomy; Humans; Kinetics; Male; Mannans; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Rectum

Investigators who perform pharmacokinetic/pharmacodynamic (PK-PD) modeling with Monte Carlo simulation have historically not stratified microbiological data by culture site. This lack of stratification might be problematic if susceptibility patterns differ among sites and might lead to differences in PK-PD.. This study compared the PK-PD of 2 antimicrobial regimens against 5 gram-negative bacterial species form 3 culture sites.. This data analysis was performed at the Department of Pharmacology, The University of Texas Health Science Center, San Antonio, Texas. Blood, pulmonary (ie, bronchial, endotracheal, lung, respiratory, sputum, and tracheal secretions), and wound distributions of MICs were extracted from the 2002 Intensive Care Unit Surveillance System database. Bacteria included Acinetobacter baumannii, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The PK properties of piperacillin/tazobactam (3.375 g every 4 hours) and piperacillin (3 g every 4 hours) were obtained from studies in healthy volunteers. Monte Carlo simulation was used in 10,000 patients for each antimicrobial-bacteria-culture site combination. The cumulative fraction of response (CFR) for a free percentage time above the MIC of > or =50% was determined for each combination, and a clinically significant difference was defined a priori as > or =10%.. Data from 2408 pulmonary, 490 blood, and 242 wound isolates were included. For piperacillin/tazobactam, the CFR varied <10% by culture site in all 5 bacterial species. Site-specific differences were noted in MIC50 for piperacillin versus E cloacae and E coli and MIC90 for piperacillin/tazobactam versus K pneumoniae and P aeruginosa. Likewise, for piperacillin, the CFR was similar among the 3 culture sites for P aeruginosa. However, the CFR for piperacillin varied by > or =10% for A baumannii (blood > wound), E cloacae (pulmonary > blood), E coli (pulmonary and blood > wound), and K pneumoniae (wound > blood).. The PK-PD models based on PK properties found in healthy humans and site-specific MIC distributions in this study suggest that for piperacillin, culture-site differences subsequently resulted in CFR differences that exceeded a predetermined level of clinical significance. Furthermore, these data suggest that traditional reporting strategies for microbiological data (ie, MIC50 and MIC90) might fail to adequately characterize the MIC population.

Topics: Anti-Bacterial Agents; Bacterial Infections; Data Interpretation, Statistical; Enzyme Inhibitors; Gram-Negative Bacteria; Humans; Microbial Sensitivity Tests; Monte Carlo Method; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Tazobactam

Treatment of intra-abdominal infections remains a challenge owing to their polymicrobial nature and associated mortality risk. Treatment regimens must provide broad-spectrum coverage, including Gram-positive and Gram-negative aerobic and anaerobic bacteria of gastrointestinal origin. Ertapenem is a long-acting 1-beta-methyl parenteral group 1 carbapenem antibiotic that has a broad antibacterial spectrum and once-daily dosing supported by clinical studies. It is active against Gram-positive and Gram-negative bacteria, including Enterobacteriaceae, Streptococcus pneumoniae and most species of anaerobic bacteria. The aim of this study was to measure the killing effects of ertapenem against a selected group of strains responsible for intra-abdominal infections. Gram-negative isolates comprised the following species: Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Klebsiella ozaenae, Enterobacter cloacae and Proteus mirabilis (extended-spectrum beta-lactamase (ESBL) producers and non-producers). Gram-positive isolates comprised methicillin-susceptible Staphylococcus aureus (MSSA), Enterococcus faecalis and anaerobic Bacteroides fragilis. Ertapenem activity was tested by determination of minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs). Killing curves were performed in monocultures and co-cultures at selected antibiotic concentrations. Ertapenem showed a rapid and potent bactericidal activity in the first few hours of the kinetic curves against E. coli (6 log(10) colony-forming unit (CFU) reduction in the first 2h), B. fragilis (4 log(10) CFU reduction in 4h), MSSA (3 log(10) CFU reduction in 4-6h), K. ozaenae (ESBL+), K. pneumoniae (ESBL+ and -), E. cloacae (ESBL-) in 1h and P. mirabilis (ESBL+) in the first 2h. The potent bactericidal activity of ertapenem compared with ceftriaxone and piperacillin/tazobactam was well demonstrated in the co-cultures of E. coli-B. fragilis and E. coli-B. fragilis-E. faecalis, whilst ertapenem was shown to be bactericidal at 24h in the mixed culture of S. aureus-P. mirabilis. These results support the potent in vitro bactericidal activity of ertapenem against all multiresistant strains selected in this study and the use of this drug in the treatment of intra-abdominal infections.

Topics: Abdomen; Anti-Bacterial Agents; Bacterial Infections; Bacteroides fragilis; beta-Lactams; Ceftazidime; Ceftriaxone; Digestive System Diseases; Enterobacter cloacae; Enterococcus faecalis; Ertapenem; Escherichia coli; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Klebsiella; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Proteus mirabilis; Staphylococcus aureus; Time Factors

Until now, studies confirming the safety of glycopeptide restriction in the empirical treatment of prolonged fever and neutropenia included only nine children. In an open-label observational study, the use of teicoplanin in paediatric oncology patients was investigated. A period of unrestricted use (2001-2003) was compared with a second period (2004) following implementation of a restrictive treatment guideline. Empirical first-line treatment consisted of piperacillin/tazobactam; in 2004, fosfomycin was added after 72 h as the second-line combination instead of teicoplanin. In total, 213 episodes (n=163 in 2001-2003; n=50 in 2004) managed with teicoplanin or fosfomycin (only 2004) were eligible. Empirical treatment of fever of unknown origin with teicoplanin was reduced by 97%. In 2004, the mean length of stay was 0.4 days shorter, no infection-related death occurred and no vancomycin-resistant enterococci were detected. Restriction of empirical glycopeptides is safe in paediatric cancer patients after first-line treatment with piperacillin/tazobactam. Fosfomycin appears to offer a feasible and cost-saving alternative in second-line combination therapy.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Drug Therapy, Combination; Female; Fever; Fever of Unknown Origin; Fosfomycin; Glycopeptides; Humans; Infant; Length of Stay; Male; Neoplasms; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Teicoplanin; Treatment Outcome

Growing resistance to antibiotics among both community-acquired and hospital pathogens is making the treatment of most infections increasingly difficult. Therefore, the aim of our multi-center study was to determine the antimicrobial susceptibility of the most frequent aerobic microorganisms isolated from children with intraabdominal infections.. Bacterial pathogens were isolated from 256 consecutive patients treated in five large specialized hospitals in Poland from January 2001 to February 2002. Minimal inhibitory concentrations (MICs) of piperacillin, piperacillin-tazobactam, cefotaxime, ceftazidime and cefepime were determined by Etests. The production of extended spectrum beta-lactamases (ESBL) was detected by a double-disk test.. Piperacillin-tazobactam was the most active agent against Enterobacteriaceae and Pseudomonas aeruginosa, inhibiting 92% and 78% of isolates respectively. Susceptibility of Enterobacteriaceae to cefotaxime, ceftazidime and cefepime was 73%, 73% and 87% respectively, and susceptibility of P. aeruginosa to both ceftazidime and cefepime was 76%. Extended-spectrum beta-lactamases were detected in 56% Klebsiella sp. and 11.5% E. coli, but the vast majority of these isolates remained susceptible to piperacillin-tazobactam (MIC(90) = 12 mg/L and MIC(90) = 1 mg/L, respectively).. Piperacillin/tazobactam remains a valuable therapeutic option in Polish pediatric patients with intraabdominal infections, due to its good activity against ESbetaL-producing organisms and P. aeruginosa.

Topics: Abdomen; Adolescent; Bacteria, Aerobic; Bacterial Infections; beta-Lactamases; Child; Child, Preschool; Drug Resistance, Bacterial; Enterobacteriaceae; Escherichia coli; Humans; Infant; Infant, Newborn; Klebsiella; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Poland; Pseudomonas aeruginosa

The aim of the study was to analyse the susceptibility of unique and non-duplicate aerobic and anaerobic isolates from surgical patients to a novel des-F(6)-quinolone (garenoxacin) and other selected antimicrobial agents.. Eleven hundred and eighty-five aerobic and anaerobic isolates from general, vascular, cardiothoracic and otolaryngologic surgical patients were tested for susceptibility to garenoxacin and seven other antibiotics (ciprofloxacin, moxifloxacin, levofloxacin, piperacillin/tazobactam, imipenem, clindamycin and metronidazole) using the referenced microbroth and agar-dilution method.. Garenoxacin exhibited greater antimicrobial activity than comparator quinolones such as ciprofloxacin, levofloxacin and other antimicrobials when tested against selected gram-positive organisms. The in vitro aerobic and anaerobic activity of garenoxacin was similar to that of moxifloxacin. All fluoroquinolones tested were effective against most gram-negative facultative anaerobes including Escherichia coli. Garenoxacin and moxifloxacin demonstrated similar in vitro antimicrobial activity against selected anaerobic gram-positive and gram-negative anaerobic bacteria such as members of the Bacteroides fragilis group. Overall, the in vitro activity of the advanced spectrum quinolones against anaerobic surgical isolates compared favourably with selected comparator agents, metronidazole, imipenem and piperacillin/tazobactam.. These findings suggest that 82.4% of aerobic surgical isolates were susceptible to a concentration of garenoxacin < or = 1.0 mg/L, whereas 84.5% of the anaerobic isolates were susceptible to a garenoxacin concentration < or = 1.0 mg/L. Garenoxacin may be a valuable surgical anti-infective for treatment of serious head and neck, soft tissue, intra-abdominal and diabetic foot infections.

Topics: Anti-Bacterial Agents; Aza Compounds; Bacteria, Aerobic; Bacteria, Anaerobic; Bacterial Infections; Fluoroquinolones; Humans; Imipenem; Metronidazole; Microbial Sensitivity Tests; Moxifloxacin; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Quinolines

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

Piperacillin/tazobactam is used for empirical therapy of severe and complex infections. We assessed its activity, 9 years after launch, against consecutive, clinically significant isolates from in-patients in UK and Ireland. Standardised disc susceptibility tests were performed on 5031 isolates at 28 hospitals. For quality assurance purposes, 5% of these isolates were collected centrally for MIC tests, as were those with exceptional resistances. Compared with a similar pre-launch survey in 1991, there were major increases in the proportions of Staphylococcus aureus, Pseudomonas aeruginosa, beta-haemolytic streptococci and Enterococcus faecium isolates collected, balanced by decreases in Escherichia coli, Proteus mirabilis and coagulase-negative staphylococci. These changes in species prevalence mostly favoured organisms with inherent resistance(s) or-in the case of S. aureus-reflected the massive increase of MRSA, up from 0.7% of all isolates in 1991 to 14.8% in 2001. Based on the disc tests, piperacillin/tazobactam retained activity against 87% of Enterobacteriaceae isolates, 95% of P. aeruginosa, 99% of streptococci and 96% of Enterococcus faecalis. Resistance nevertheless had increased since 1991 in E. coli from 4 to 10%, Klebsiella spp. (5 to 21%) and in AmpC-inducible Enterobacteriaceae (17 to 23%), though not in P. mirabilis or P. aeruginosa. MIC tests confirmed most of the piperacillin/tazobactam resistance found by disc tests in Enterobacter spp., but indicated susceptibility for about half of the E. coli isolates recorded as resistant in disc tests. This situation might be remedied by reducing the zone breakpoint, but this would increase the "false susceptible" rate unacceptably. Thus, if disc tests suggest that an isolate is marginally resistant to piperacillin/tazobactam and the drug is sought as therapy, it is recommended that MIC be determined with, e.g., an Etest.

Topics: Bacteria; Bacterial Infections; Cephalosporins; Drug Resistance, Bacterial; Drug Therapy, Combination; Enterobacteriaceae; Gram-Negative Bacteria; Humans; In Vitro Techniques; Ireland; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Time Factors; United Kingdom

The in vitro activity of ertapenem against bacterial pathogens isolated from patients with moderate to severe complicated intra-abdominal, complicated skin/skin structure, acute pelvic, or complicated urinary tract infection or community acquired pneumonia was compared to ceftriaxone and piperacillin-tazobactam and related to known plasma concentrations of the three agents. Ertapenem was more potent against methicillin-susceptible Staphylococcus aureus (MSSA) than ceftriaxone and piperacillin-tazobactam and was more potent and more active than both of these agents against Enterobacteriaceae and anaerobes. Piperacillin-tazobactam was the most active agent against enterococci and Pseudomonas aeruginosa. All isolates of Enterobacteriaceae (n=1088), Streptococcus pyogenes (n=37), Streptococcus agalactiae (n=48), MSSA (n=187), Haemophilus influenzae (n=59), and Moraxella catarrhalis (n=9) were susceptible to ertapenem; < 1% of 1284 anaerobes and only 1 of 113 Streptococcus pneumoniae (a penicillin-resistant isolate) were resistant to ertapenem. The MIC value at which 90% of all Enterobacteriaceae, streptococci, MSSA, H. influenzae, M. catarrhalis, and anaerobes were inhibited (MIC90) was < or = 1 microg/ml and below the mean plasma concentration of total ertapenem following a 1 g intravenous infusion for at least 24 hours, i.e., the entire recommended dosing interval, and below the free drug concentration for at least 8 h.

Topics: Anti-Bacterial Agents; Bacterial Infections; beta-Lactams; Ceftriaxone; Community-Acquired Infections; Drug Resistance, Microbial; Drug Therapy, Combination; Enterobacteriaceae; Ertapenem; Haemophilus influenzae; Humans; Lactams; Microbial Sensitivity Tests; Moraxella catarrhalis; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Staphylococcus aureus; Streptococcus agalactiae; Streptococcus pyogenes

Treatment of diabetic foot infections (DFIs) represents an important challenge for surgeons, especially in light of the poor results achieved by traditional therapeutic approaches. In this study, the clinical and bacteriological efficacy of TZP for treatment of DFIs in 38 outpatients was evaluated. All patients (median age 63 yrs) were affected by DFIs to different degrees of severity according to Wagner's classification: degree 0, 7 pts; degree 1, 17 pts; degree 2, 10 pts; degree 3, 4 pts. Degree 0-1 infections underwent a 10-18 day course with TZP given i.m. (2.25 g bid); degree 2-3 infections were initially treated with TZP i.v. (4.5 g bid or tid). Some patients began treatment in hospital and after early discharge continued parenteral therapy at home; others were treated exclusively at home. Some pts, after a 5-7-day course of i.v. therapy switched to i.m. route. The average duration of antibiotic therapy was 28 days. At the end of treatment with TZP, some patients underwent a new treatment with oral coamoxi-clav for 10-15 days. A bacteriological examination was done for all patients: ulcus (degree 1) and deep tissue (degree 2-3) swabs at the first surgical toilette. Clinical controls, medications, surgical toilettes and microbiological cultures were performed according to the degree of severity, extension of the lesion and response to treatment. All cultures were positive for polymicrobial infections (Staphylococcus spp, Enterococcus spp, Enterobacteriaceae, Pseudomonas spp). In 30/38 pts (79%) a complete resolution was observed; in 4 pts (10%) an improvement. DFIs require long term parenteral treatment, with wide spectrum antibiotics including Gram +, Gram - and anaerobes. OPAT represents a valid alternative to hospitalisation when the general conditions of the patient are stable, the infection is not too severe and complications are not present. TZP proved to be a good choice for treatment of diabetic foot infections that, due to its high safety, can be successfully utilized also in OPAT programmes

Topics: Adult; Aged; Ambulatory Care; Anti-Bacterial Agents; Bacterial Infections; Diabetic Foot; Female; Humans; Injections; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies

To compare the cost, efficacy and cost efficacy of tazobactam/piperacillin and imipenem/cilastatin in the treatment of intra-abdominal infection.. The analysis was retrospective and based on a decision tree. Effectiveness data were obtained from 19 published clinical trials. Direct costs were quantified per patient from the time the decision was made to administer the antibacterial to the end of the first course of treatment or the end of a subsequent course of treatment, if required. The primary end-point was the cost per successfully treated patient. The cost per life saved was also analysed. Various follow-up times were taken into account.. German National Health Insurance funds.. 1744 patients with intra-abdominal infection.. Tazobactam/piperacillin (total daily dosage of 13.5 g/day) and imipenem/cilastatin (total daily dosage of 1.5 to 4 g/day). The mean duration of treatment varied from 5.5 to 8.2 days for tazobactam/piperacillin and 5 to 9.4 days for imipenem/cilastatin.. Compared with imipenem/cilastatin, treatment with tazobactam/piperacillin was more effective and the overall treatment costs were lower. In the base-case analysis, the cost-efficacy ratio (cost per successfully treated patient) was 7881 German deutschmarks (DM) for tazobactam/piperacillin and DM11,390 for imipenem/cilastatin. The incremental cost-efficacy ratio (per life saved) varied between -DM72,567 and -DM350,738 for tazobactam/piperacillin. Sensitivity analyses revealed that the results were robust against various assumptions on cost parameters, clinical outcomes and length of treatment. All costs reflect 1998 values; $US1 = DM1.85.. This study suggests that compared with imipenem/cilastatin, tazobactam/piperacillin is more cost efficacious in the treatment of intra-abdominal infections and that it offers a cost advantage through fewer relapses and lower daily therapeutic costs.

Topics: Abdomen; Adult; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Cost-Benefit Analysis; Decision Trees; Drug Combinations; Drug Costs; Drug Therapy, Combination; Health Care Costs; Humans; Imipenem; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Protease Inhibitors; Randomized Controlled Trials as Topic; Retrospective Studies; Thienamycins

Combining tazobactam, a beta-lactamase inhibitor, with the ureidopenicillin, piperacillin, successfully restores the activity of piperacillin against beta-lactamase producing bacteria. Thus, piperacillin/tazobactam is highly active against most clinically important species of Gram-negative and Gram-positive bacteria, including anaerobes. We evaluated the in vitro activity of piperacillin/tazobactam against clinical isolates from a tertiary university hospital located in Sao Paulo, Brazil. Its activity was compared to that of ticarcillin/clavulanic acid, ampicillin/sulbactam, ceftazidime, ceftriaxone, cefotaxime, cefoxitin, aztreonam, and imipenem against 820 isolates (608 Gram-negative and 212 Gram-positive) collected from hospitalized patients in 1999. The most frequent species tested were Pseudomonas aeruginosa (168/20%), Escherichia coli (139/17%), Acinetobacter spp. (131/16%), and Staphylococcus aureus (76/9%). Of the isolates studied, 30% were from the bloodstream, 16% from the lower respiratory tract, and 11% from surgical wounds or soft tissue. The isolates were susceptibility tested by the broth microdilution method according to NCCLS procedures. The isolates tested were highly resistant to most antimicrobial agents evaluated. Imipenem resistance was not verified among Enterobacteriaceae, and piperacillin/tazobactam was the second most active beta-lactams against this group of bacteria (80.0% susceptibility). Extended-spectrum beta-lactamase production was very high among E. coli (approximately 20%) and Klebsiella pneumoniae (approximately 40%). Imipenem was uniformly active against these species (100% susceptibility) and piperacillin/tazobactam was the second most active compound inhibiting 84.4% of isolates. Pseudomonas aeruginosa was highly resistant to all beta-lactams evaluated and piperacillin/tazobactam was the most active compound against this species. Our results demonstrate an extremely high level of antimicrobial resistance in the hospital evaluated, especially among non-enteric Gram-negative bacilli. Due to this high level of resistance, piperacillin/tazobactam represents an important contribution to the treatment of nosocomial infections.

Topics: Bacteria; Bacterial Infections; beta-Lactams; Brazil; Cross Infection; Drug Resistance, Microbial; Drug Resistance, Multiple; Drug Therapy, Combination; Hospitals, University; Humans; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

Topics: Bacterial Infections; Clinical Trials as Topic; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination