piperacillin--tazobactam-drug-combination and Intraabdominal-Infections

Topics: Anti-Bacterial Agents; Carbapenems; Humans; Intraabdominal Infections; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sepsis

An increase in the prevalence of antimicrobial resistance among gram-negative pathogens has been noted recently. A challenge in empiric treatment of complicated intra-abdominal infection (cIAI) is identifying initial appropriate antibiotic therapy, which is associated with reduced length of stay and mortality compared with inappropriate therapy. The objective of this study was to assess the cost-effectiveness of ceftolozane/tazobactam + metronidazole compared with piperacillin/tazobactam (commonly used in this indication) in the treatment of patients with cIAI in UK hospitals.. A decision-analytic Monte Carlo simulation model was used to compare costs (antibiotic and hospitalization costs) and quality-adjusted life years (QALYs) of patients infected with gram-negative cIAI and treated empirically with either ceftolozane/tazobactam + metronidazole or piperacillin/tazobactam. Bacterial isolates were randomly drawn from the Program to Assess Ceftolozane/Tazobactam Susceptibility (PACTS) database, a surveillance database of non-duplicate bacterial isolates collected from patients in the UK infected with gram-negative pathogens. Susceptibility to initial empiric therapy was based on the measured susceptibilities reported in the PACTS database.. Ceftolozane/tazobactam + metronidazole was cost-effective when compared with piperacillin/tazobactam, with an incremental cost-effectiveness ratio (ICER) of £4,350/QALY and 0.36 hospitalization days/patient saved. Costs in the ceftolozane/tazobactam + metronidazole arm were £2,576/patient, compared with £2,168/patient in the piperacillin/tazobactam arm. The ceftolozane/tazobactam + metronidazole arm experienced a greater number of QALYs than the piperacillin/tazobactam arm (14.31/patient vs 14.21/patient, respectively). Ceftolozane/tazobactam + metronidazole remained cost-effective in one-way sensitivity and probabilistic sensitivity analyses.. Economic models can help to identify the appropriate choice of empiric therapy for the treatment of cIAI. Results indicated that empiric use of ceftolozane/tazobactam + metronidazole is cost-effective vs piperacillin/tazobactam in UK patients with cIAI at risk of resistant infection. This will be valuable to commissioners and clinicians to aid decision-making on the targeting of resources for appropriate antibiotic therapy under the premise of antimicrobial stewardship.

Topics: Anti-Bacterial Agents; Bacteriological Techniques; Cephalosporins; Clinical Protocols; Drug Combinations; Drug Therapy, Combination; Female; Gram-Negative Bacterial Infections; Humans; Intraabdominal Infections; Male; Metronidazole; Models, Econometric; Monte Carlo Method; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Quality-Adjusted Life Years; Tazobactam; United Kingdom

This study investigated the clinical features of anaerobic bacteraemia in an acute-care hospital, and evaluated the antimicrobial susceptibility of these isolates to commonly available antibiotics. Microbiological and epidemiological data from 2009 to 2011were extracted from the laboratory information system and electronic medical records. One hundred and eleven unique patient episodes consisting of 116 anaerobic isolates were selected for clinical review and antibiotic susceptibility testing. Susceptibilities to amoxicillin-clavulanate, clindamycin, imipenem, metronidazole, moxifloxacin, penicillin and piperacillin-tazobactam were performed using Etest strips with categorical interpretations according to current CLSI breakpoints. Metronidazole-resistant and carbapenem-resistant anaerobic Gram-negative bacilli were screened for the nim and cfiA genes. Clinical data was obtained retrospectively from electronic medical records. During the 3 year period, Bacteroides fragilis group (41%), Clostridium species (14%), Propionibacterium species (9%) and Fusobacterium species (6%) were the most commonly isolated anaerobes. Patients with anaerobic bacteraemia that were included in the study were predominantly above 60 years of age, with community-acquired infections. The most commonly used empiric antibiotic therapies were beta-lactam/beta-lactamase inhibitor combinations (44%) and metronidazole (10%). The crude mortality was 25%, and appropriate initial antibiotic therapy was not significantly associated with improved survival. Intra-abdominal infections (39%) and soft-tissue infections (33%) accounted for nearly three-quarters of all bacteraemia. Antibiotics with the best anaerobic activity were imipenem, piperacillin-tazobactam, amoxicillin-clavulanate and metronidazole, with in-vitro susceptibility rates of 95%, 95%, 94% and 92% respectively. Susceptibilities to penicillin (31%), clindamycin (60%) and moxifloxacin (84%) were more variable. Two multidrug-resistant isolates of Bacteroides species were positive for nim and cfiA genes respectively, while another two imipenem-resistant Fusobacterium species were negative for cfiA genes. This study demonstrated that anaerobic bacteraemia in our patient population was predominantly associated with intra-abdominal and soft-tissue infections. Overall antibiotic resistance was high for penicillin and clindamycin, and the presence of emerging resistance to carbapenems and metronidazole warrants further monitoring.

Topics: Anaerobiosis; Anti-Infective Agents; Bacteremia; Bacteria, Anaerobic; Bacteroides; Carbapenems; Clindamycin; Clostridium; Drug Resistance, Microbial; Fusobacterium; Gram-Positive Bacteria; Humans; Intraabdominal Infections; Metronidazole; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Propionibacterium; Retrospective Studies

Gram-negative ESKAPE pathogens (Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) are responsible for increases in antimicrobial-resistant infections worldwide. We determined in vitro susceptibilities to eight parenteral antimicrobial agents using Clinical and Laboratory Standards Institute broth microdilution methodology for Gram-negative ESKAPE pathogens isolated from hospitalized patients with intra-abdominal infections (IAIs) (n=3052) and urinary tract infections (UTIs) (n=1088) in 11 Asia-Pacific countries/regions from 2013 to 2015. Amikacin (98.3, 96.4 %), imipenem (97.1, 95.5 %) and ertapenem (95.3, 93.2 %) demonstrated the highest rates of susceptibility for isolates of K. pneumoniae from IAI and UTI, respectively, whereas susceptibility to advanced-generation cephalosporins was <84 and <71 %, respectively. K. pneumoniae with an extended-spectrum β-lactamase-positive phenotype were more common in UTI (27.1 %) than IAI (16.2 %). Imipenem and amikacin were the most active agents against extended-spectrum β-lactamase-positive K. pneumoniae from IAI (95.1, 91.8 %) and UTI (94.9, 92.3 %), respectively, whereas <54 % were susceptible to piperacillin-tazobactam. Against Enterobacter spp. and P. aeruginosa, amikacin demonstrated the highest rates of susceptibility for isolates from IAI (99.7, 95.5 %) and UTI (90.9, 91.5 %), respectively. K. pneumoniae, Enterobacter spp. and P. aeruginosa from urine demonstrated lower susceptibility to levofloxacin (74.1, 81.8 and 73.8 %) than from IAI (87.6, 91.8 and 85.4 %). For A. baumannii, rates of susceptibility to all agents tested were <43 %. We conclude that the studied Gram-negative ESKAPE pathogens demonstrated reduced susceptibility to commonly prescribed advanced-generation cephalosporins, piperacillin-tazobactam and levofloxacin, while amikacin and carbapenems were the most active. Ongoing surveillance to monitor evolving resistance trends and the development of novel antimicrobial agents with potent activity against Gram-negative ESKAPE pathogens are mandatory.

Topics: Acinetobacter baumannii; Amikacin; Anti-Infective Agents; Asia; beta-Lactamases; beta-Lactams; Carbapenems; Cephalosporins; Drug Resistance, Multiple, Bacterial; Enterobacter; Ertapenem; Gram-Negative Bacteria; Hospitalization; Humans; Imipenem; Intraabdominal Infections; Klebsiella pneumoniae; Levofloxacin; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Urinary Tract Infections

Sub-inhibitory concentrations of antibiotics are always generated as a consequence of antimicrobial therapy and the effects of such residual products in bacterial morphology are well documented, especially the filamentation generated by beta-lactams. The aim of this study was to investigate some morphological and pathological aspects (virulence factors) of Escherichia coli cultivated under half-minimum inhibitory concentration (1.0 µg/mL) of piperacillin-tazobactam (PTZ sub-MIC). PTZ sub-MIC promoted noticeable changes in the bacterial cells which reach the peak of morphological alterations (filamentation) and complexity at 16 h of antimicrobial exposure. Thereafter the filamentous cells and a control one, not treated with PTZ, were comparatively tested for growth curve; biochemical profile; oxidative stress tolerance; biofilm production and cell hydrophobicity; motility and pathogenicity in vivo. PTZ sub-MIC attenuated the E. coli growth rate, but without changes in carbohydrate fermentation or in traditional biochemical tests. Overall, the treatment of E. coli with sub-MIC of PTZ generated filamentous forms which were accompanied by the inhibition of virulence factors such as the oxidative stress response, biofilm formation, cell surface hydrophobicity, and motility. These results are consistent with the reduced pathogenicity observed for the filamentous E. coli in the murine model of intra-abdominal infection. In other words, the treatment of E. coli with sub-MIC of PTZ suggests a decrease in their virulence.

Topics: Animals; Anti-Bacterial Agents; Biofilms; Disease Models, Animal; Escherichia coli; Escherichia coli Infections; Intraabdominal Infections; Locomotion; Metabolism; Mice; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Virulence

To evaluate the antimicrobial susceptibility of Gram-negative bacilli that caused hospital-acquired and community-acquired intra-abdominal infections (IAIs) in China between 2012 and 2013, we determined the susceptibilities to 12 antimicrobials and the extended-spectrum β-lactamase (ESBL) statuses of 3,540 IAI isolates from seven geographic areas in China in a central laboratory using CLSI broth microdilution and interpretive standards. Most infections were caused by Escherichia coli (46.3%) and Klebsiella pneumoniae (19.7%). Rates of ESBL-producing E. coli (P = 0.031), K. pneumoniae (P = 0.017), and Proteus mirabilis (P = 0.004) were higher in hospital-acquired IAIs than in community-acquired IAIs. Susceptibilities of enterobacteriaceae to ertapenem, amikacin, piperacillin-tazobactam, and imipenem were 71.3% to 100%, 81.3% to 100%, 64.7% to 100%, and 83.1% to 100%, respectively, but imipenem was ineffective against P. mirabilis (<20%). Although most ESBL-positive hospital-acquired isolates were resistant to third- and fourth-generation cephalosporins, the majority were susceptible to cefoxitin (47.9% to 83.9%). Susceptibilities of ESBL-positive isolates to ampicillin-sulbactam (<10%) were low, whereas susceptibilities to ciprofloxacin (0% to 54.6%) and levofloxacin (0% to 63.6%) varied substantially. The prevalences of cephalosporin-susceptible E. coli and K. pneumoniae were higher in the northeastern and southern regions than in the central and eastern regions, reflecting the ESBL-positive rates in these areas, and were lowest in the Jiangsu-Zhejiang (Jiang-Zhe) area where the rates of carbapenem resistance were also highest. Ertapenem, amikacin, piperacillin-tazobactam, and imipenem are the most efficacious antibiotics for treating IAIs in China, especially those caused by E. coli or K. pneumoniae. Resistance to cephalosporins and carbapenems is more common in the Jiang-Zhe area than in other regions in China.

Topics: Amikacin; Ampicillin; Anti-Bacterial Agents; beta-Lactamases; beta-Lactams; Cefoxitin; China; Ciprofloxacin; Community-Acquired Infections; Cross Infection; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Ertapenem; Gene Expression; Humans; Imipenem; Intraabdominal Infections; Levofloxacin; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sulbactam

It is unknown if β-lactam monotherapy is sufficient for complicated intra-abdominal infections or if broader coverage is required, such as with vancomycin. This study sought to determine the clinical outcomes of piperacillin/tazobactam (PIP/TAZ) monotherapy compared to combination therapy with vancomycin and PIP/TAZ for complicated intra-abdominal infections among patients within a surgical intensive care unit (ICU).. Retrospective cohort study.. Three surgical ICUs at a tertiary academic medical center.. Four hundred seventeen patients with a secondary peritonitis identified by International Classification of Diseases, Ninth Revision codes who received either PIP/TAZ monotherapy (228 patients) or PIP/TAZ and vancomycin combination therapy (189 patients).. The primary outcome was day 28 clinical cure; secondary outcomes included day 7 clinical cure, length of stay (LOS), and mortality. There were no statistically significant differences between the monotherapy and combination therapy groups with respect to day 28 clinical cure (33.9% vs 25.5%, p=0.064), day 7 clinical cure (23.6% vs 17.6%, p=0.14), or 28-day mortality (7% vs 7.9%, p=0.72). LOS in the ICU was significantly shorter in the monotherapy group (6 days) compared with the combination therapy group (7 days; p=0.04); however, hospital LOS was not significantly different.. No difference was observed in clinical cure rates at day 28 or day 7 between those who received PIP/TAZ monotherapy compared to PIP/TAZ and vancomycin combination therapy.

Topics: Academic Medical Centers; Aged; Anti-Bacterial Agents; Cohort Studies; Drug Therapy, Combination; Female; Humans; Intensive Care Units; Intraabdominal Infections; Length of Stay; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Time Factors; Treatment Outcome; Vancomycin

The microbial susceptibility of many antibiotics has been affected by prescribing patterns and their extensive use. The purpose of this evaluation was to assess how these changes could affect the initial efficacy of ertapenem and piperacillin/tazobactam in the treatment of complicated intra-abdominal infections (IAIs) acquired in the community and the potential consequences this may have in healthcare costs in Spain.. The Initial efficacy of ertapenem and piperacillin/tazobactam for patients with APACHE (Acute Physiology and Chronic Health Evaluation) II scores <10 was extracted from a multicenter randomized study and were combined with the current microbial susceptibilities obtained from the SMART study, a multinational surveillance program. Country-specific pathogens distribution was extracted from a national study in patients with community-acquired IAI. The estimated effectiveness was used in a decision-analytic model to compare total costs between ertapenem and piperacillin/tazobactam in the treatment of complicated IAI. The model performs extensive one-way and probabilistic sensitivity analyses.. The model suggested a savings of €209 (year 2012 values) per patient when complicated IAIs acquired in the community (APACHE II <10) were treated with ertapenem instead of piperacillin/tazobactam. One-way sensitivity analyses showed length of stay as the key driver parameter. Further analysis of this parameter and probabilistic sensitivity analysis confirmed the robustness of our evaluation, with a 58% likelihood of ertapenem being dominant.. Ertapenem appears to be a cost-saving strategy over piperacillin/tazobactam for the treatment of patients with complicated IAIs acquired in the community in Spain.

Topics: Anti-Bacterial Agents; APACHE; beta-Lactams; Clinical Trials, Phase III as Topic; Community-Acquired Infections; Cost-Benefit Analysis; Decision Trees; Double-Blind Method; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Ertapenem; Humans; Intraabdominal Infections; Length of Stay; Models, Economic; Monte Carlo Method; Multicenter Studies as Topic; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Spain

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

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

Escherichia coli is commonly involved in infections with a heavy bacterial burden. Piperacillin-tazobactam and carbapenems are among the recommended empirical treatments for health care-associated complicated intra-abdominal infections. In contrast to amoxicillin-clavulanate, both have reduced in vitro activity in the presence of high concentrations of extended-spectrum β-lactamase (ESBL)-producing and non-ESBL-producing E. coli bacteria. Our goal was to compare the efficacy of these antimicrobials against different concentrations of two clinical E. coli strains, one an ESBL-producer and the other a non-ESBL-producer, in a murine sepsis model. An experimental sepsis model {~5.5 log10 CFU/g [low inoculum concentration (LI)] or ~7.5 log(10) CFU/g [high inoculum concentration (HI)]} using E. coli strains ATCC 25922 (non-ESBL producer) and Ec1062 (CTX-M-14 producer), which are susceptible to the three antimicrobials, was used. Amoxicillin-clavulanate (50/12.5 mg/kg given intramuscularly [i.m.]), piperacillin-tazobactam (25/3.125 mg/kg given intraperitoneally [i.p.]), and imipenem (30 mg/kg i.m.) were used. Piperacillin-tazobactam and imipenem reduced spleen ATCC 25922 strain concentrations (-2.53 and -2.14 log10 CFU/g [P < 0.05, respectively]) in the HI versus LI groups, while amoxicillin-clavulanate maintained its efficacy (-1.01 log10 CFU/g [no statistically significant difference]). Regarding the Ec1062 strain, the antimicrobials showed lower efficacy in the HI than in the LI groups: -0.73, -1.89, and -1.62 log10 CFU/g (P < 0.05, for piperacillin-tazobactam, imipenem, and amoxicillin-clavulanate, respectively, although imipenem and amoxicillin-clavulanate were more efficacious than piperacillin-tazobactam). An adapted imipenem treatment (based on the time for which the serum drug concentration remained above the MIC obtained with a HI of the ATCC 25922 strain) improved its efficacy to -1.67 log10 CFU/g (P < 0.05). These results suggest that amoxicillin-clavulanate could be an alternative to imipenem treatment of infections caused by ESBL- and non-ESBL-producing E. coli strains in patients with therapeutic failure with piperacillin-tazobactam.

Topics: Amoxicillin-Potassium Clavulanate Combination; Animals; Anti-Bacterial Agents; beta-Lactamases; Colony Count, Microbial; Escherichia coli; Escherichia coli Infections; Female; Imipenem; Injections, Intramuscular; Injections, Intraperitoneal; Intraabdominal Infections; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis; Treatment Outcome

Complicated intra-abdominal infections (cIAI) are a common problem in surgical practice. The effect of body mass index (BMI) on the outcome is poorly understood. We compared the association of BMI and type of antibiotic therapy for cIAI described in a previously published trial of ertapenem vs. piperacillin-tazobactam (Namias N, Solomkin JS, Jensen EH, et al. Randomized, multicenter, double-blind study of efficacy, safety, and tolerability of intravenous ertapenem versus piperacillin/tazobactam in treatment of complicated intra-abdominal infections in hospitalized adults. Surg Infect 2007;8:15-28).. A post-hoc analysis was performed using data obtained from the published study. The effect of BMI and type of antibiotic used for therapy were calculated for clinically favorable outcomes at early follow-up assessment (EFA).. The 231 patients who were microbiologically evaluable at EFA were stratified by BMI (<30 or ≥30 kg/m(2)). Twelve patients were excluded because of missing BMI data, leaving 219 patients for analysis. There were some differences in baseline characteristics between patients with a BMI <30 kg/m(2), including the source of intra-abdominal infection (more appendicitis in BMI <30 group; p=0.01) and gender (more men in the BMI <30 group; p=0.03). There was no difference in cure rates between the groups (82.9% for BMI <30 kg/m(2) vs. 74.5% for those with BMI ≥30 kg/m(2); 8% difference in proportions, 95% confidence interval [CI] -5%, 25%). There was an 80% favorable clinical response to ertapenem in the BMI <30 group compared with an 81% favorable rate in the BMI ≥30 group (-1% difference in proportions; 95% CI -22%, 19%). This compared with an 86% favorable response rate to piperacillin-tazobactam in the BMI <30 group vs. a 65% favorable clinical response rate in the BMI ≥30 group (21% difference in proportions; 95% CI -1%, 47%).. There was no difference in the cure rate of patients with cIAI in the BMI <30 and BMI ≥30 kg/m(2) groups. There were no statistically significant differences in the likelihood of response to an antibiotic regimen. However, there was a nominally 21% lower cure rate in the high BMI group receiving piperacillin-tazobactam (86% vs. 65%; 21% difference in proportions; 95% CI -1%, 47%), whereas there was only a 1% difference in the cure rate between BMI groups in the patients receiving ertapenem. This difference may be related to gender and etiology of infection. Although limited by the small number of high BMI patients and post-hoc methodology, these results merit consideration of the design of future prospective antibiotic trials to include stratification for BMI and consideration of the effect of BMI on pharmacokinetics and pharmacodynamics.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactams; Body Mass Index; Ertapenem; Female; Humans; Intraabdominal Infections; Male; Middle Aged; Multicenter Studies as Topic; Obesity, Morbid; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Randomized Controlled Trials as Topic; Young Adult

The Study for Monitoring Antimicrobial Resistance Trends (SMART) is an international surveillance study designed to monitor resistance trends among aerobic and facultative Gram-negative bacilli (GNB) isolated from intra-abdominal infections. During 2003-2010, a total of 20710 GNB isolates were collected at medical centers in China, Hong Kong, Korea, New Zealand, and Taiwan. The susceptibility profiles of 2252 isolates of non-Enterobacteriaceae GNB were determined. At least 10 isolates of a given organism were required for that organism to be included in the analysis. Pseudomonas aeruginosa was the leading organism (49.2% of non-Enterobacteriaceae GNB), followed by Acinetobacter baumannii (21.5%), Aeromonas spp. (11.6%), and Stenotrophomonas maltophilia (9.1%). All the other species/genera made up less than 2%. The rates of susceptibility of the four major organisms were examined for two different time periods and according to whether the isolates had been obtained <48 h after hospitalization or ≥ 48 h after hospital admission. P. aeruginosa, Aeromonas spp., and S. maltophilia showed sustained levels of susceptibility to several antimicrobial agents in the two time periods, whereas A. baumannii exhibited very high rates of resistance to most antimicrobial agents including imipenem. Nosocomial P. aeruginosa and A. baumannii were more resistant than community-acquired pathogens, although this was not the case for Aeromonas spp. and S. maltophilia. Worldwide and regional surveillance is necessary to guide empirical antimicrobial therapy for infections due to non-Enterobacteriaceae GNB.

Topics: Acinetobacter Infections; Aeromonas; Anti-Bacterial Agents; Asia; Australasia; Drug Resistance, Bacterial; Humans; Imipenem; Intraabdominal Infections; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Population Surveillance; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections