piperacillin--tazobactam-drug-combination and Cross-Infection

Identifying risk factors predicting acquisition of resistant. MEDLINE®, EMBASE®, and Cochrane Central were searched between 2000 and 2016 for studies examining independent risk factors associated with acquisition of resistant. Of the 54 eligible articles, 28 publications (31studies) examined multi-drug resistant (MDR) or extensively drug resistant (XDR). Prior use of antibiotics and prior hospital or ICU stay was the most significant risk factors for acquisition of resistant

Topics: Adult; Aged; Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Cephalosporins; Critical Care; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Humans; Intensive Care Units; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections; Quinolones; Risk Factors; Vancomycin

Piperacillin-tazobactam (PIP/TAZO) has been extensively used in adults with nosocomial infections and with fever and neutropenia. The available data considering the use of PIP/TAZO have not been reviewed in detail.. Review discussing the use of PIP/TAZO in neonatal and paediatric patients.. Medline search focusing on articles published in English. Owing to the paucity of randomized controlled trails, uncontrolled studies and case series were included.. PIP/TAZO may safely be used in paediatric patients as an empiric treatment for serious infections in hospital environments where resistance to common first-line antimicrobials has emerged. The most common indications in paediatric patients are nosocomial infections owing to resistant Gram-negatives, exacerbation of pulmonary colonization with Psuedomonas aeruginosa in patients with cystic fibrosis, intra-abdominal infections, fever and neutropenia in paediatric cancer patients. The influence of PIP/TAZO routine use on the selection of extended-spectrum beta-lactamase producing Gram-negatives and on the prevalence of vancomycin-resistant enterococci is still a matter of debate. In particular the use of PIP/TAZO in neonates and PIP/TAZO monotherapy in paediatric cancer patients with fever and neutropenia should be investigated in prospective randomized studies including a sufficient number of patients.

Topics: Anti-Bacterial Agents; Child; Clinical Trials as Topic; Cross Infection; Humans; Infant, Newborn; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

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

Due to limited therapeutic options, the spread of extended-spectrum beta-lactamases (ESBLs) have become a major public health concern. We conducted a prospective, randomized, open-label comparison of the therapeutic efficacy of piperacillin-tazobactam (PTZ), cefepime, and ertapenem in febrile nosocomial urinary tract infection with ESBL-producing Escherichia coli (ESBL-EC).. This study was conducted at three university hospitals between January 2013 and August 2015. Hospitalized adult patients presenting with fever were screened for healthcare-associated urinary tract infection (HA-UTI). When ESBL-EC was solely detected and susceptible to a randomized antibiotic in vitro, the case was included in the final analysis. Participants were treated for 10-14 days with PTZ, cefepime, or ertapenem.. A total of 66 participants were evenly assigned to the PTZ and ertapenem treatment groups. After the recruitment of six participants, assignment to the cefepime treatment group was stopped because of an unexpectedly high treatment failure rate. The baseline characteristics of these participants did not differ from participants in other treatment groups. The clinical and microbiological response to PTZ treatment was estimated to be 94% and was similar to the response to ertapenem treatment. The efficacy of cefepime was 33.3%. In the cefepime group, age, Charlson comorbidity index, genotype, and minimal inhibitory concentration (MIC) did not significantly affect the success of treatment. Similarly, genotype seemed to be irrelevant with respect to clinical outcome in the PTZ group. Expired cases tended to involve septic shock with a high Charlson comorbidity index and high MIC.. Results from this study suggest that PTZ is effective in the treatment of urinary tract infection caused by ESBL-EC when the in vitro test indicates susceptibility. In addition, cefepime should not be used as an alternative treatment for urinary tract infection caused by ESBL-EC.. The trial was registered with the Clinical Research Information Service of Korea Centers for Disease Control and Prevention. (KCT0001895).

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Cefepime; Cephalosporins; Cross Infection; Ertapenem; Escherichia coli; Escherichia coli Infections; Female; Genotype; Humans; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Republic of Korea; Tazobactam; Urinary Tract Infections

The purpose of this study was to assess the pharmacokinetic (PK) characteristics, clinical efficiency, and pharmacoeconomic parameters of piperacillin/tazobactam administered by extended infusion (EI) or intermittent infusion (II) in the treatment of hospital-acquired pneumonia (HAP) in critically ill patients with low illness severity in China. Fifty patients completed the study, with 25 patients receiving 4/0.5 g piperacillin/tazobactam over 30 min as the II group and 25 patients receiving 4/0.5 g piperacillin/tazobactam over 3 h every 6 h as the EI group. Drug assay was performed using high-performance liquid chromatography (HPLC). The percentage of the dosing interval for which the free piperacillin concentration (%fT) exceeds the minimum inhibitory concentration (MIC) was calculated. The patients' therapy cost, clinical efficiency, and adverse effects were also recorded. %fT>MIC was about 100, 98.73, and 93.04 % in the EI arm versus 81.48, 53.29, and 42.15 % in the II arm, respectively, when the microorganism responsible for HAP had an MIC of 4, 8, and 16 mg/L. The therapy cost in the EI group was lower than that of the II group ($1351.72 ± 120.39 vs. $1782.04 ± 164.51, p = 0.001). However, the clinical success rate, clinical failure rate, and drug-related adverse events did not significantly differ between groups. EI treatment with piperacillin/tazobactam was a cost-effective approach to the management of HAP, being equally clinically effective to conventional II.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamase Inhibitors; China; Chromatography, High Pressure Liquid; Costs and Cost Analysis; Critical Illness; Cross Infection; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Infusions, Intravenous; Male; Microbial Sensitivity Tests; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Plasma; Pneumonia, Bacterial; Treatment Outcome; Young Adult

There is lack of information on the efficacy and safety of piperacillin–tazobactam administered by continuous infusion.. The aim of this study was to investigate whether continuous infusion of piperacillin–tazobactam is superior in terms of efficacy to a 30 % higher dose administered by intermittent infusion to treat suspected or confirmed infection due to Pseudomonas aeruginosa. Setting Multicenter clinical trial with 11 third level Spanish hospitals.. Randomized, double-blind parallel-group clinical trial, controlled by conventional administration of the drug. Patients randomly assigned in a 1:1 ratio to receive piperacillin–tazobactam as continuous infusion (CI) or intermittent (II).. Primary efficacy endpoint was percentage of patients having a satisfactory clinical response at completion of treatment, defined as clinical cure or clinical improvement. Adverse events were reported. Results 78 patients were included, 40 in the CI group and 38 in the II group. Mean (standard deviation) duration of treatment was 7 (±4.44) days. 58 patients (74.4 %) experienced cure or improvement at the end of the treatment. There were no statistical differences in cure rates between the two treatment arms and no adverse events were reported.. Continuous infusion of piperacillin–tazobactam is an alternative administration drug method at least similar in efficacy and safety to conventional intermittent infusion. Multivariate analysis is needed to determine whether continuous administration might be more beneficial than intermittent in certain patient subgroups.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Load; Cross Infection; Double-Blind Method; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections; Remission Induction; Spain; Time Factors; Treatment Outcome; Young Adult

To observe the serum concentration and evaluate clinical efficacy of piperacillin/tazobactam (TZP) prolonged infusion time in treatment of hospital acquired pneumonia (HAP).. Fifty HAP patients admitted to intensive care unit (ICU) from March 1 to October 31, 2012 were enrolled. The bacterial drug sensitivity results showed that the minimum inhibitory concentration (MIC) of TZP was 8 mg/L or 16 mg/L. According to completely randomized grouping method, the patients were divided into treatment group (n=25) and control group (n=25). The therapeutic regimen in control group was TZP 4.5 g, in regular infusion every 6 hours and finished in 30 minutes; the treatment group was TZP 4.5 g, in prolonged infusion every 6 hours by using infusion pump for continuous intravenous infusion 3 hours. Acute physiology and chronic health evaluation II(APACHEII) score, clinical pulmonary infection score (CPIS) and procalcitonin (PCT) level were compared between the two groups 3 days after treatment. The treatment success rate, remedial treatment rate, antibiotic costs were recorded in both groups. Blood specimen was collected at 0.5, 1, 2, 3, 4, 6 hours at the beginning of administration, and the blood drug concentration of piperacillin and tazobactam was determined using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS).. The PCT (2.16±0.17 μg/L vs. 4.77±0.25 μg/L), CPIS score(6.21±1.14 μg/L vs. 6.92±1.35 μg/L) and remedial treatment rate (12.0% vs. 52.0%) of the treatment group were significantly lower than those of the control group after administration for 3 days (P<0.05 or P<0.01), and APACHEII score was slightly lower than that in control group (21.38±7.37 vs. 22.15±5.46, P>0.05). After active remedial treatment, there were no significant difference in the treatment success rate (88.0% vs. 80.0%) and relapse rate (4.2% vs. 7.7%) between treatment group and control group (both P>0.05). But the antibiotic costs in treatment group were significantly lower than that of control group (4330.38±1087.24 Yuan vs. 5506.15±1361.73 Yuan, P<0.01). The treatment course of antibacterials in treatment group was significantly shorter than that in control group (6.00±1.05 days vs. 8.20±1.03 days, P<0.01). The infection by Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae was monitored, TZP serum concentration administrated at 0.5-6 hours in the treatment group was higher than MIC, but in the control group, TZP blood concentration was lower than MIC after administration for 2-3 hours. In treatment group, the percentage of duration of blood drug level higher than MIC account for dosing interval (%T>MIC) was 86.82%, while in the control group, the %T>MIC was 42.84%.. TZP prolonged the infusion time dosing regimens using in Gram negative bacteria induced by high MIC value of HAP have more stable plasma concentration, curative clinical effect and reduce the cost of treatment.

Topics: Aged; Anti-Bacterial Agents; Cross Infection; Drug Administration Schedule; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Prospective Studies

ß-Lactam antibiotics demonstrate time-dependent killing. Prolonged infusion of these agents is commonly performed to optimize the time the unbound concentration of an antibiotic remains greater than the minimum inhibitory concentration and decrease costs, despite limited evidence suggesting improved clinical results.. To determine whether prolonged infusion of ß-lactam antibiotics improves outcomes in critically ill patients with suspected gram-negative infection.. We conducted a single-center, before-after, comparative effectiveness trial between January 2010 and January 2011 in the intensive care units at Barnes-Jewish Hospital, an urban teaching hospital affiliated with the Washington University School of Medicine in St. Louis, MO. Outcomes were compared between patients who received standardized dosing of meropenem, piperacillin-tazobactam, or cefepime as an intermittent infusion over 30 minutes (January 1, 2010, to June 30, 2010) and patients who received prolonged infusion over 3 hours (August 1, 2010, to January 31, 2011).. A total of 503 patients (intermittent infusion, n = 242; prolonged infusion, n = 261) treated for gram-negative infection were included in the clinically evaluable population. Approximately 50% of patients in each group received cefepime and 20% received piperacillin-tazobactam. More patients in the intermittent infusion group received meropenem (35.5% vs 24.5%; p = 0.007). Baseline characteristics were similar between groups, with the exception of a greater occurrence of chronic obstructive pulmonary disease (COPD) in the intermittent infusion group. Treatment success rates in the clinically evaluable group were 56.6% for intermittent infusion and 51.0% for prolonged infusion (p = 0.204), and in the microbiologically evaluable population, 55.2% for intermittent infusion and 49.5% for prolonged infusion (p = 0.486). Fourteen-day, 30-day, and inhospital mortality rates in the clinically evaluable population for the intermittent and prolonged infusion groups were 13.2% versus 18.0% (p = 0.141), 23.6% versus 25.7% (p = 0.582), and 19.4% versus 23.0% (p = 0.329).. Routine use of prolonged infusion of time-dependent antibiotics for the empiric treatment of gram-negative bacterial infections offers no advantage over intermittent infusion antibiotic therapy with regard to treatment success, mortality, or hospital length of stay. These results were confirmed after controlling for potential confounders in a multivariate analysis.

Topics: Aged; Anti-Bacterial Agents; beta-Lactams; Cefepime; Cephalosporins; Cohort Studies; Cross Infection; Drug Administration Schedule; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Hospitals, Teaching; Hospitals, Urban; Humans; Infusions, Intravenous; Intensive Care Units; Length of Stay; Male; Meropenem; Middle Aged; Missouri; Penicillanic Acid; Pilot Projects; Piperacillin; Piperacillin, Tazobactam Drug Combination; Thienamycins

Healthcare-associated pneumonia (HCAP) may have a more severe course than community-acquired pneumonia (CAP); hence, it is more likely to be caused by drug-resistant bacterial pathogens and anaerobes involved in aspiration pneumonia. We compared the efficacy and safety of initial empiric therapy with piperacillin/tazobactam (PIPC/TAZ, 13.5 g/day) with that of meropenem (MEPM, 1.5 g/day) as single broad-spectrum regimens with gram-negative and anaerobic coverage in patients with HCAP in Japan. The clinical cure rate was 75.9 % (22/29 cases) in the PIPC/TAZ group and 64.3 % (18/28 cases) in the MEPM group. The clinical efficacy rate was 87.9 % (29/33 cases) in the PIPC/TAZ group and 74.2 % (23/31 cases) in the MEPM group. The bacteriological eradication rate was 94.4 % (17/18) in the PIPC/TAZ group and 87.5 % (14/16) in the MEPM group. Adverse drug reactions were seen in 22.4 % (11/49 cases) of patients in the PIPC/TAZ group and 17.4 % (8/46 cases) of patients in the MEPM group. Although not statistically different, the PIPC/TAZ group had a slightly higher efficacy rate than the MEPM group. Both treatment regimens are tolerable and might be appropriate to use as initial empiric therapy for HCAP in Japan. To investigate the differences in efficacy profiles of those two regimens, a further confirmatory study with a larger cohort as determined by a power analysis is recommended.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Cross Infection; Female; Humans; Japan; Male; Meropenem; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Prospective Studies; Statistics, Nonparametric; Thienamycins; 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

In the present study 24 hospitalized patients requiring empirical antibiotic treatment were randomly assigned to receive the beta-lactam antibiotic/beta-lactamase inhibitor combination piperacillin-tazobactam either as an intermittent or as a continuous infusion. According to pharmacokinetic modelling, the daily dose was reduced by 33% in patients receiving continuous infusion compared with intermittent infusion. Dose reduction because of impaired renal function was required in the intermittent dosing group for 5 of 12 patients compared with 1 of 12 patients in the continuous infusion group. However, the mean daily dose in the continuous group was 15% less than the intermittent infusion group. Mean serum concentrations of piperacillin were to 39.0 microg/ml after the end of bolus distribution, exceeding by far the minimal inhibitory concentration of the most clinically relevant pathogens. The corresponding mean value for tazobactam was 6.3 microg/ml. Pharmacokinetic/pharmacodynamic modelling suggests that both treatment schemes should produce virtually identical anti-infective responses to sensitive, intermediate and resistant strains. In the present study the continuous infusion of piperacillin/tazobactam provided adequate antibacterial activity over the 24-h dosing period and offers the potential for a substantial reduction in the total daily dose.

Topics: Adult; Aged; Anti-Bacterial Agents; Cholangitis; Community-Acquired Infections; Cross Infection; Drug Administration Schedule; Female; Fever of Unknown Origin; Hospitalization; Humans; Infections; Infusions, Intravenous; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia; Prospective Studies; Treatment Outcome; Urinary Tract Infections

To compare clinical and bacteriological efficacy as well as tolerability of two regimens of broad-spectrum antibiotics (ceftazidime versus piperacillin/tazobactam) combined with amikacin in the treatment of nosocomial pneumonia in intensive care patients.. Open label, prospective, multicenter, and randomized phase III clinical trial.. Medical or surgical intensive care units (ICUs) of nine acute-care teaching hospitals in Spain.. One hundred and twenty-four ICU patients with nosocomial pneumonia and requiring mechanical ventilation were included. They were randomized to receive amikacin (15 mg/day divided into two doses) combined with either piperacillin (4 g every 6 h) and tazobactam (0.5 g every 6 h) (n = 88) or ceftazidime (2 g every 8 h) (n = 36).. The causative pathogen was determined in 60.2% of patients in the group of amikacin plus piperacillin/tazobactam and in 76.9% in the group of amikacin plus ceftazidime. A total of 94 bacterial organisms were isolated among which gram-negative bacilli predominated, Pseudomonas aeruginosa being the most frequent. Clinical response at the end of antibiotic therapy was considered satisfactory (cure and/or improvement) in 63.9% of patients in the amikacin plus piperacillin/tazobactam group and in 61.5% in the amikacin plus ceftazidime (odds ratio 1.1; 95% confidence interval 0.44-2.75). Eradication or presumptive eradication rates for each pathogen and for either gram-negative or gram-positive bacteria were similar in both antibiotic combinations (odds ratio 1.2; 95% confidence interval 0.39-3.66). A total of 21 adverse effects (23.9%) occurred in the amikacin plus piperacillin and tazobactam group and six (16.7%) in the amikacin plus ceftazidime group, thrombocytosis, renal dysfunction, and hepatic cytolysis being the most common. The efficacy and tolerability of the two therapeutic regimens were similar not only in the whole study population, but also in the subset of P. aeruginosa-related pneumonia (odds ratio 1; 95% confidence interval 0.08-13.37).. Amikacin associated with either ceftazidime or piperacillin and tazobactam has shown comparable efficacy and tolerability in the treatment of ICU patients with nosocomial pneumonia.

Topics: Aged; Amikacin; Ceftazidime; Cephalosporins; Critical Care; Cross Infection; Drug Therapy, Combination; Female; Hospital Mortality; Hospitals, Teaching; Humans; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Proportional Hazards Models; Prospective Studies; Spain; Survival Analysis; Treatment Outcome

An open, randomized, multicenter study was conducted to compare the efficacy and safety of piperacillin/tazobactam and co-amoxiclav plus aminoglycoside in the treatment of hospitalized patients with severe community-acquired or nosocomial pneumonia. Of the 89 patients who entered the study, 84 (94%) were clinically evaluable. A favorable clinical response was observed in 90% of the piperacillin/ tazobactam group and in 84% of the co-amoxiclav/aminoglycoside group (not significant). The bacteriological efficacy was comparable in both groups (96% vs. 92%; not significant). There was only one fatal outcome in the piperacillin/tazobactam group compared to six in the co-amoxiclav/aminoglycoside group regimen (P=0.058). The adverse event rate was non-significantly lower in the piperacillin/ tazobactam group compared to the co-amoxiclav/aminoglycoside group (2% vs. 7%; P=0.32). Piperacillin/tazobactam is safe and highly efficacious in the treatment of serious pneumonia in hospitalized patients. It compares favorably with the combination of co-amoxiclav/aminoglycoside.

Topics: Aged; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Community-Acquired Infections; Cross Infection; Drug Therapy, Combination; Female; Gentamicins; Humans; Male; Middle Aged; Netilmicin; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Treatment Outcome

It is well documented that inappropriate use of antimicrobials is the major driver of antimicrobial resistance. To combat this, antibiotic stewardship has been demonstrated to reduce antibiotic usage, decrease the prevalence of resistance, lead to significant economic gains and better patients' outcomes. In Nigeria, antimicrobial guidelines for critically ill patients in intensive care units (ICUs), with infections are scarce. We set out to develop antimicrobial guidelines for this category of patients.. A committee of 12 experts, consisting of Clinical Microbiologists, Intensivists, Infectious Disease Physicians, Surgeons, and Anesthesiologists, collaborated to develop guidelines for managing infections in critically ill patients in Nigerian ICUs. The guidelines were based on evidence from published data and local prospective antibiograms from three ICUs in Lagos, Nigeria. The committee considered the availability of appropriate antimicrobial drugs in hospital formularies. Proposed recommendations were approved by consensus agreement among committee members.. Candida albicans and Pseudomonas aeruginosa were the most common microorganisms isolated from the 3 ICUs, followed by Klebsiella pneumoniae, Acinetobacter baumannii, and Escherichia coli. Targeted therapy is recognized as the best approach in patient management. Based on various antibiograms and publications from different hospitals across the country, amikacin is recommended as the most effective empiric antibiotic against Enterobacterales and A. baumannii, while colistin and polymixin B showed high efficacy against all bacteria. Amoxicillin-clavulanate or ceftriaxone was recommended as the first-choice drug for community-acquired (CA) CA-pneumonia while piperacillin-tazobactam + amikacin was recommended as first choice for the treatment of healthcare-associated (HA) HA-pneumonia. For ventilatorassociated pneumonia (VAP), the consensus for the drug of first choice was agreed as meropenem. Amoxycillin-clavulanate +clindamycin was the consensus choice for CAskin and soft tissue infection (SSIS) and piperacillin-tazobactam + metronidazole ±vancomycin for HA-SSIS. Ceftriaxone-tazobactam or piperacillin-tazobactam + gentamicin was consensus for CA-blood stream infections (BSI) with first choice+regimen for HA-BSI being meropenem/piperacillin-tazobactam +amikacin +fluconazole. For community-acquired urinary tract infection (UTI), first choice antibiotic was ciprofloxacin or ceftriaxone with a catheter-associated UTI (CAUTI) regimen of first choice being meropenem + fluconazole.. Data from a multicenter three ICU surveillance and antibiograms and publications from different hospitals in the country was used to produce this evidence-based Nigerian-specific antimicrobial treatment guidelines of critically ill patients in ICUs by a group of experts from different specialties in Nigeria. The implementation of this guideline will facilitate learning, continuous improvement of stewardship activities and provide a baseline for updating of guidelines to reflect evolving antibiotic needs.. Il est bien établi que l’utilisation inappropriée des antimicrobiens est le principal moteur de la résistance aux antimicrobiens. Pour lutter contre ce phénomène, il a été démontré que la bonne gestion des antibiotiques permettait de réduire l’utilisation des antibiotiques, de diminuer la prévalence de la résistance, de réaliser des gains économiques significatifs et d’améliorer les résultats pour les patients. Au Nigéria, les directives antimicrobiennes pour les patients gravement malades dans les unités de soins intensifs (USI), souffrant d’infections, sont rares. Nous avons entrepris d’élaborer des lignes directrices sur les antimicrobiens pour cette catégorie de patients.. Un comité de 12 experts, composé de microbiologistes cliniques, d’intensivistes, de médecins spécialistes des maladies infectieuses, de chirurgiens et d’anesthésistes, a collaboré à l’élaboration de lignes directrices pour la prise en charge des infections chez les patients gravement malades dans les unités de soins intensifs nigérianes. Les lignes directrices sont basées sur des données publiées et des antibiogrammes prospectifs locaux provenant de trois unités de soins intensifs de Lagos, au Nigeria. Le comité a pris en compte la disponibilité des médicaments antimicrobiens appropriés dans les formulaires des hôpitaux. Les recommandations proposées ont été approuvées par consensus entre les membres du comité.. Candida albicans et Pseudomonas aeruginosa étaient les microorganismes les plus fréquemment isolés dans les trois unités de soins intensifs, suivis par Klebsiella pneumoniae, Acinetobacter baumannii et Escherichia coli. La thérapie ciblée est reconnue comme la meilleure approche pour la prise en charge des patients. Sur la base de divers antibiogrammes et publications provenant de différents hôpitaux du pays, l'amikacine est recommandée comme l'antibiotique empirique le plus efficace contre les entérobactéries et A. baumannii, tandis que la colistine et la polymixine B se sont révélées très efficaces contre toutes les bactéries. L'amoxicilline-clavulanate ou la ceftriaxone ont été recommandées comme médicaments de premier choix pour les pneumonies communautaires, tandis que la pipéracilline-tazobactam + amikacine ont été recommandées comme médicaments de premier choix pour le traitement des pneumonies associées aux soins. Pour les pneumonies acquises sous ventilation mécanique (PAV), le consensus sur le médicament de premier choix est le méropénem. L'amoxycilline-clavulanate +clindamycine était le choix consensuel pour les infections de la peau et des tissus mous et la pipéracilline-tazobactam + métronidazole ±vancomycine pour les infections de la peau et des tissus mous. HA-SSIS. Ceftriaxone-tazobactam ou pipéracilline-tazobactam + gentamicine a fait l'objet d'un consensus pour les infections de la circulation sanguine de l'AC (BSI), le premier choix de régime pour les HA-BSI étant le méropénem/pipéracilline-tazobactam +amikacine +fluconazole. Pour les infections urinaires communautaires, l'antibiotique de premier choix était la ciprofloxacine ou la ceftriaxone, le régime de premier choix pour les infections urinaires associées à un cathéter étant le meropenem +fluconazole.. Les données issues d’une surveillance multicentrique de trois unités de soins intensifs, d’antibiogrammes et de publications de différents hôpitaux du pays ont été utilisées par un groupe d’experts de différentes spécialités nigérianes pour élaborer ces lignes directrices sur le traitement antimicrobien des patients gravement malades dans les unités de soins intensifs, fondées sur des données probantes et spécifiques au Nigeria. La mise en œuvre de ces lignes directrices facilitera l’apprentissage, l’amélioration continue des activités de gestion et fournira une base de référence pour la mise à jour des lignes directrices afin de refléter l’évolution des besoins en antibiotiques.. Antimicrobiens, Résistance aux antimicrobiens, Gestion des antibiotiques, Lignes directrices, Soins intensifs, Unité de soins intensifs, Infections associées aux soins de santé.

Topics: Amikacin; Anti-Bacterial Agents; Anti-Infective Agents; Ceftriaxone; Clavulanic Acid; Community-Acquired Infections; Critical Illness; Cross Infection; Fluconazole; Humans; Meropenem; Microbial Sensitivity Tests; Nigeria; Piperacillin, Tazobactam Drug Combination; Pneumonia; Prospective Studies; Urinary Tract Infections

Carbapenem-resistant Enterobacteriales has become a threat in Taiwan. This is the first local study focusing on the association between carbapenem-resistant Enterobacteriales and antimicrobial consumption. From January 2012 to December 2020, data were collected in a tertiary care hospital in Taipei, Taiwan. Antimicrobial consumption was estimated by the defined daily dose/1,000 patient-days. During the same period, the prevalence of carbapenem-resistant Escherichia coli (CREC) and carbapenem-resistant Klebsiella pneumoniae (CRKP) were collected through routine surveillance data. The following retrospective analyses were conducted: 1) analysis of antimicrobial consumption over time, (2) analysis and forecast of CREC and CRKP prevalence over time, and 3) analysis of correlation between antimicrobial consumption and the prevalence of CREC and CRKP. The consumption of piperacillin/tazobactam (β = 0.615), fluoroquinolones (β = 0.856), meropenem (β = 0.819), and doripenem (β = 0.891) increased during the observation period (P < 0.001), and the consumption of aminoglycosides (β = -0.852) and imipenem/cilastatin (β = -0.851) decreased (P < 0.001). The prevalence of CRKP rose over time (β = 0.522, P = 0.001) and correlated positively with the consumption of fluoroquinolones, levofloxacin, penicillin/β-lactamase inhibitor, piperacillin/tazobactam, meropenem, and doripenem (P < 0.05). The prevalence of CRKP and CREC both correlated negatively with consumption of aminoglycosides (P < 0.01). The prevalence of CRKP in our hospital increased as the forecast predicted based on an autoregressive integrated moving average model. This study provides alarming messages for members participating in antimicrobial stewardship programs, including the increasing prevalence of CRKP, the increasing consumption of broad-spectrum antibiotics, and the positive correlation between them.

Topics: Aminoglycosides; Anti-Bacterial Agents; Anti-Infective Agents; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Cross Infection; Doripenem; Escherichia coli; Fluoroquinolones; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Piperacillin, Tazobactam Drug Combination; Prevalence; Retrospective Studies; Taiwan; Tertiary Care Centers

To compare the rate of therapeutic failure in critically ill patients treated by third-generation cephalosporins (3GCs) or piperacillin-tazobactam (PTZ) for wild-type AmpC-producing Enterobacterales pulmonary infections.. Over a 4-year period, all adult patients treated for a wild-type AmpC-producing Enterobacterales pulmonary infection were retrospectively included. Two groups of patients were compared according to the definitive antibiotic therapy (3GCs or PTZ) considered after <48 h of empirical antibiotic therapy. The main outcome was the rate of therapeutic failure (impaired clinical response under treatment and/or a relapse of pulmonary infection). The secondary outcome was a secondary acquisition of 3GCs resistance.. Over the study period, 244 patients were included; 56 (23%) experienced therapeutic failure. In the non-adjusted cohort, the rate of therapeutic failure and emergence of resistance were significantly higher in the 3GCs group (32 vs. 18%, p = .011 and 13 vs. 5%, p = .035, respectively). In the propensity score-matched population, the use of 3GCs was associated with higher rates of therapeutic failure (HR = 1.61 [1.27-2.07]). The secondary de-escalation to 3GCs after 48 h of PTZ as a first-line antibiotic therapy was not associated with increased rate of emergence of resistance.. Our study confirms that 3GCs should be avoided as first-line antibiotic therapy in wild-type AmpC-producing Enterobacterales pulmonary infections.

Topics: Aged; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cephalosporins; Critical Illness; Cross Infection; Enterobacter; Family Characteristics; Female; Hospitals; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Penicillanic Acid; Piperacillin, Tazobactam Drug Combination; Pneumonia, Ventilator-Associated; Retrospective Studies; Ventilators, Mechanical

Cefoperazone-sulbactam (CS) and piperacillin-tazobactam (TZP) are used in the treatment of Gram-negative nosocomial infections (NIs). We aimed to compare the effects of these two antibiotics on mortality and treatment success. Patients treated with CS or TZP empirically for at least three days with suspicion of NI were included in this retrospective study. In total, 308 (154 patients in both treatment arms) patients were analyzed. Treatment success rate in CS and TZP group respectively (50% vs 51.2%,

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Cefoperazone; Cross Infection; Drug Combinations; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sulbactam

Piperacillin/tazobactam (TZP ) is commonly used against multi-resistant nosocomial. A 73-year-old-man experienced severe pulmonary hemorrhage and bloody diarrhea during the treatment with TZP for. Platelet dysfunction is a little-known mechanism of TZP-induced bleeding. This is the second reported case of TZP-related bleeding that has been attributed to platelet dysfunction, and the first case report that has not been associated with surgery. While thrombocytopenia is easily recognized, this form of TZP-induced bleeding can be detected only by platelet functional tests.

Topics: Aged; Anti-Bacterial Agents; Blood Platelet Disorders; Cross Infection; Humans; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Ventilator-Associated

Topics: Anti-Bacterial Agents; Child; Child, Preschool; Cross Infection; Female; Humans; Infant; Male; Microbial Sensitivity Tests; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Tazobactam

To determine the percentage of patients given standard doses of piperacillin/tazobactam or meropenem by continuous  infusion who achieved the target pharmacokinetic/pharmacodynamic  (PK/PD) index, which was defined as free concentrations four times  more than the minimum inhibitory concentration (CMI) for 100% of the  dosing interval (100% fT≥ 4 x MIC).. Preliminary data from a larger prospective clinical study  analysing the PK/PD behaviour of β-lactams antibiotics continuous  infusion (CI) in critical patients. The study was conducted in the  intensive care units of a tertiary university hospital for adults (June  2015-May 2017). Inclusion criteria: normal renal function (glomerular  renal function (GFR) CKD-EPI formula ≥ 60 mL/min/1.73 m2) and  treatment with standard dose β-lactams CI. Concentrations at steady  state (Css) conditions were determined using UHPLC-MS/MS. We  selected the highest susceptible MIC for all likely organisms according to  European Commitee on Antimicrobial Susceptibility Testing's (i.e.  piperacillin/tazobactam: 8 mg/L for enterobacteriaceae and 16 mg/L for  Pseudomonas aeruginosa; meropenem: 2 mg/L for any  microorganism). In addition, a subanalysis of patients was conducted using actual MIC values.. 61 patients were enrolled (25 to meropenem and 36 to  piperacillin/tazobactam). Average age was 59 (15) years and median  GFR rate was 95 mL/min/1.73 m2 (83-115). Median meropenem and  piperacillin free concentrations were 16 mg/L (11-29) and 40 mg/L (21- 51), respectively. 88% of patients treated with meropenem reached the  PK/PD target, without differences between both microorganisms. For  piperacillin/tazobactam, 61% and 11% of patients reached the target,  with enterobacteriaceae and Pseudomonas as suspected  microorganisms, respectively. The pathogen was isolated in 35 (57%)  patients: 94% reached the target PK/PD, without differences between  both antibiotic therapies.. Standard doses of meropenem CI are sufficient to  achieve a PK/PD target of 100% fT≥ 4 x MIC in suspected infections  with high MICs (Pseudomonas aeruginosa or enterobacteriaceae).  However, higher doses of piperacillin/tazobactam could be considered to  achieve this goal. In patients with isolated microorganisms, a  standard dose of both antibiotic therapies would be sufficient to achieve  the target. Therapeutic drug monitoring is highly recommended for  therapeutic optimization.. Objetivo: Determinar el porcentaje de pacientes, a los que se les  administró dosis estándar de piperacilina/tazobactam o meropenem en  perfusión continua, que alcanzaban el índice  farmacocinético/farmacodinámico diana definido como el 100% del  intervalo de administración en que las concentraciones de antibiótico  libre fueron cuatro veces iguales o superiores a la concentración mínima  inhibitoria (100% fT ≥ 4 x CMI).Método: Datos preliminares obtenidos de un estudio clínico prospectivo que analiza el comportamiento  farmacocinético/farmacodinámico de los antibióticos betalactámicos  administrados en perfusión continua en pacientes críticos. Se realizó en  unidades de cuidados intensivos de un hospital universitario de tercer  nivel, desde junio de 2015 a mayo de 2017. Criterios de inclusión:  adultos con función renal correcta (filtrado glomerular según la fórmula  CKD-EPI ≥ 60 ml/min/1,73 m2) y tratados con dosis estándar de  antibióticos betalactámicos en perfusión continua. Las concentraciones  en estado de equilibrio estacionario fueron determinadas mediante  cromatografía líquida acoplada a espectrometría de masas (UHPLC- MS/MS). Se utilizaron valores de concentración mínima  inhibitoria  teóricos para microorganismos más resistentes (piperacilina/ tazobactam: 16 mg/l para Pseudomonas aeruginosa y 8 mg/l para Enterobacteriaceae; meropenem: 2 mg/l, independientemente del  microorganismo). Además, se realizó un subanálisis de los pacientes con aislamiento microbiológico (concentraciones mínimas inhibitorias  reales).Resultados: Se incluyeron 61 pacientes (25 meropenem y 36  piperacilina/ tazobactam). Edad media 59 años (15), mediana de  filtrado glomerular 95 ml/min/1,73 m2 (83-115). Mediana de  concentraciones en estado de equilibrio estacionario libre: 16 mg/l (11- 29) meropenem y 40 mg/l (21-51) piperacilina. El 88% de los pacientes  tratados con meropenem alcanzaron el objetivo  farmacocinético/farmacodinámico, sin diferencias entre Enterobacteriaceae y Pseudomonas. En el caso de  piperacilina/tazobactam, el 61% y el 11% de los pacientes alcanzaron la  diana, considerando Enterobacteriaceae y Pseudomonas como  microorganismo sospechoso. Un total de 35 (57%) pacientes  presentaron aislamiento microbiológico. El 94% de ellos alcanzaron la  diana, sin diferencias entre los dos antibióticos.Conclusiones: Ante la sospecha de infecciones por microorganismos con concentraciones mínimas inhibitorias elevadas  (Pseudomonas aeruginosa o enterobacterias),

Topics: Adult; Aged; Anti-Bacterial Agents; Clinical Studies as Topic; Critical Illness; Cross Infection; Enterobacteriaceae Infections; Female; Hospitals, University; Humans; Infusions, Intravenous; Intensive Care Units; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Pseudomonas Infections; Tertiary Care Centers

Pseudomonas aeruginosa bacteraemia is associated with a very high mortality, conditioned by comorbidity, source, severity of the episode and lack of adequate treatment. The aim of the study is to know the mortality and prognostic factors of bacteraemia by P.aeruginosa in our hospital.. We conducted a retrospective study of P.aeruginosa bacteraemia detected between 2009 and 2014. Epidemiological, clinical and microbiological characteristics were described. A risk factor analysis for mortality was performed.. We analysed 110 episodes of bacteraemia, which was more frequent in men of advanced age and with a history of hospitalisation, comorbidity and immunosuppression. Most of the bacteraemias were secondary (mainly of respiratory or urinary source) and led to a significant clinical deterioration. The presence of antibiotic resistance was very high, with 27.3% of multiresistant strains. Empirical treatment was adequate in 60.0% and 92.3% for definite treatment. Overall mortality was 37.3% and attributable mortality was 29.1%. The most important prognostic factors were Charlson index ≥3, history of haematologic malignancy, neutropenia and previous use of corticosteroids, source of bacteraemia, Pitt index ≥4, renal insufficiency, adequate definite treatment, empiric treatment with piperacillin/tazobactam in severe episodes and focus control.. P.aeruginosa bacteraemia is associated with a very high mortality, possibly more related to previous comorbidity and severity of the episode than to the treatment chosen. However, the main goal in management remains to optimise treatment, including focus control.

Topics: Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Community-Acquired Infections; Comorbidity; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Hospitalization; Humans; Immunocompromised Host; Male; Middle Aged; Neoplasms; Piperacillin, Tazobactam Drug Combination; Prognosis; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Spain; Tertiary Care Centers

Topics: Anti-Bacterial Agents; Carbapenems; Cephalosporins; Cross Infection; Cross-Sectional Studies; Drug Resistance, Multiple, Bacterial; Hospitals; Humans; Intensive Care Units; Microbial Sensitivity Tests; Piperacillin, Tazobactam Drug Combination; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; United States

Elizabethkingia meningoseptica is a non-fermentative Gram-negative bacillus that has emerged as an important pathogen in nosocomial infections and is usually associated with high mortality. E. meningoseptica is inherently resistant to many broad-spectrum antibiotics, and appropriate antibiotic selection is crucial for survival. Data about the therapeutic efficacy of fluoroquinolone in E. meningoseptica bacteraemia are limited. We retrospectively enrolled patients with E. meningoseptica bacteraemia who were treated with a single antimicrobial agent with in vitro activity against E. meningoseptica for at least 48 hours in a Taiwanese medical centre between January 2011 and June 2016. We compared the therapeutic efficacy of fluoroquinolone and non-fluoroquinolone treatment. A logistic regression and a propensity score-adjusted model were used to evaluate the risk factors for 14-day mortality. A total of 66 patients were identified, 24 who received fluoroquinolone treatment (ciprofloxacin, n = 9; levofloxacin, n = 15) and 42 who received non-fluoroquinolone treatment (piperacillin/tazobactam, n = 26; trimethoprim/sulfamethoxazole, n = 15; minocycline, n = 1). The fluoroquinolone group had significantly lower 14-day mortality than the non-fluoroquinolone group (8.3% vs. 33.3%, P = 0.023). The APACHE II score was significantly higher in the non-fluoroquinolone group than in the fluoroquinolone group. In a propensity-adjusted analysis, fluoroquinolone use was an independent factor associated with 14-day survival. After stratification using the APACHE II score, treatment with fluoroquinolone was associated with 14-day survival, but did not reach statistical significance in both groups with greater and lesser severity. Therefore, fluoroquinolone is a suitable antimicrobial agent for treating E. meningoseptica bacteraemia.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Chryseobacterium; Cross Infection; Female; Flavobacteriaceae Infections; Fluoroquinolones; Humans; Male; Microbial Sensitivity Tests; Minocycline; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Taiwan; Trimethoprim, Sulfamethoxazole Drug Combination

 Drug supply bottleneck is a worldwide challenge, e. g. the antibiotics Piperacillin/Tazobactam shortage in 2016/2017. The efficacy of an appropriate replacement management was evaluated at the University Hospital Frankfurt (UHF)..  The Antibiotic-Stewardship (ABS)-Team at UHF decreed a restriction of PIP/TAZ and provided alternative antibiotic therapy recommendations during the shortage period. Consequences of this intervention on antibiotic consumption and overall costs were investigated..  Over 12-weeks, PIP/TAZ-mean application rate was reduced by 71 % and was predominantly used to treat hospital acquired pneumonia (62 %), febrile neutropenian children (12 %), followed by other indications (< 10 %, each). Alternative substances' use increased (Ceftazidim + 229 %, Imipenem/Cilastatin + 18 %, Meropenem + 27 %, Ceftriaxon + 26 %, Levofloxacin + 11 %, Ciprofloxacin + 14 %, Ampicillin/Sulbactam + 83 %), however the overall antibiotic consumption declined by -5.8 % (cost savings: 13 %). Simultaneously, additional personnel costs have been noted (+ 4300 €). The evidence rate of bloodstream infections with resistant bacteria and detection of Clostridium-difficile-toxin were both not significantly elevated, compared to windows just ahead, after and one year before intervention period..  Drug shortages challenge hospital antibiotic-stewardship programs by enforced use of broad spectrum-antibiotics, endanger patient safety and require rational replacement strategies, following infectious diseases- and microbiological outlines. Whilst personnel expenditures are higher, antimicrobial-stewardship interventions may successfully contribute to prevent additional medication costs..  Arzneimittel-Lieferengpässe stellen ein zunehmendes Problem dar, wie z. B. im Fall des Breitspektrum-Antibiotikums Piperacillin/Tazobactam (PIP/TAZ) in 2016/2017. Die Effektivität eines aktiven Ausfallmanagements am Universitätsklinikum Frankfurt (UKF) soll bewertet werden..  Das Antibiotic-Stewardship (ABS) -Team des UKF beschloss klinikumsweit den restriktiven Einsatz von PIP/TAZ und empfahl alternative Antibiotikatherapien im Zeitraum des Lieferengpasses. Die Konsequenzen dieser Intervention auf Antibiotikaeinsatz und Kosten wurden retrospektiv untersucht..  Über 12 Wochen wurde der Verbrauch von PIP/TAZ um durchschnittlich 71 % reduziert. Im Interventionszeitraum wurde PIP/TAZ vorwiegend zur Behandlung nosokomialer Pneumonien (62 %) und Fieber in der Neutropenie bei Kindern (12 %) eingesetzt, andere Indikationen lagen bei jeweils < 10 %. Der Verbrauch der Alternativsubstanzen stieg prozentual an (Ceftazidim + 229 %, Imipenem/Cilastatin + 18 %, Meropenem + 27 %, Ceftriaxon + 26 %, Levofloxacin + 11 %, Ciprofloxacin + 14 %, Ampicillin/Sulbactam + 83 %), insgesamt sank der Antibiotikaverbrauch jedoch um 5,8 % (Kostenersparnis: 13 %), bei moderat ansteigenden Personalkosten (+ 4300,- €). Die Rate nachgewiesener Blutstrominfektionen mit resistenten Bakterien und Clostridium difficile-Toxinnachweise im Stuhl waren nicht signifikant erhöht, verglichen mit Zeiträumen direkt vor und nach Intervention sowie ein Jahr zuvor..  Lieferengpässe untergraben die Ziele des Antibiotic-Stewardship durch erzwungenen Einsatz von Breitspektrum-Antibiotika, bedrohen potenziell die Patientensicherheit und erfordern ein Ausfallmanagement nach mikrobiologisch-infektiologisch sinnvollen Kriterien. Bei moderat erhöhtem Personalaufwand können Antibiotic-Stewardship-Maßnahmen erfolgreich beitragen, Mehrkosten für Arzneimittel zu vermeiden.

Topics: Anti-Bacterial Agents; Antimicrobial Stewardship; Cross Infection; Hospitals; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Practice Guidelines as Topic

The ongoing extended spectrum β-lactamase-producing. This ward-level multicentre retrospective study was based on data from French antibiotic and multidrug-resistant bacteria surveillance networks in healthcare facilities. Antibiotic use was expressed in defined daily doses per 1000 patient-days. Factors associated with the reduction in carbapenem use (yes/no) over the study period were determined from random-effects logistic regression model (493 wards nested within 259 healthcare facilities): ward characteristics (type, size…), ward antibiotic use (initial antibiotic use [i.e., consumption of a given antibiotic in 2009], initial antibiotic prescribing profile [i.e., proportion of a given antibiotic in the overall antibiotic consumption in 2009] and reduction in the use of a given antibiotic between 2009 and 2013) and regional ESBL-PE incidence rate in acute care settings in 2011.. Our study suggests that a decrease in 3GCs in the overall antibiotic use and the continuation of reduction in fluoroquinolone use, could allow reducing carbapenem use, given the well-demonstrated role of 3GCs and fluoroquinolones in the occurrence of ESBL-PE. Thus, antibiotic stewardship programs should target wards with higher 3GC prescription proportions to reduce them.

Topics: Anti-Bacterial Agents; Antimicrobial Stewardship; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Cephalosporins; Cross Infection; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Fluoroquinolones; France; Glycopeptides; Guidelines as Topic; Hospitals; Humans; Intensive Care Units; Logistic Models; Piperacillin, Tazobactam Drug Combination; Practice Patterns, Physicians'; Prescriptions; Probability; Retrospective Studies

　Tazobactam/piperacillin (TAZ/PIPC) is an antimicrobial drug agent with a broad spectrum of antibacterial activity and is recommended as first-line therapy for hospital-acquired pneumonia, nursing- and healthcare-associated pneumonia, and other severe pneumonias. Nevertheless, in clinical settings, TAZ/PIPC is not fully effective in the treatment of pneumonia in the elderly. In the present study, we retrospectively investigated the efficacy of TAZ/PIPC for pneumonia in elderly patients and identified factors that reduced its efficacy. Ninety-nine patients (mean age of 83.4 years and no significant difference in the sex ratio) were included in the present study. The efficacy rate of TAZ/PIPC for pneumonia in elderly patients was 81.8%, which was approximately 7 to 10% lower than that in domestic phase III trials. A multivariate analysis identified the complications of chronic respiratory disease as a significant factor attenuating the therapeutic effects of TAZ/PIPC [odds ratio 4.050, 95% confidence interval (CI) 1.008-16.271]. In conclusion, TAZ/PIPC may not be sufficiently effective for pneumonia in elderly patients with the complications of chronic respiratory disease as a background.

Topics: Age Factors; Aged; Aged, 80 and over; Anti-Bacterial Agents; Chronic Disease; Cross Infection; Female; Hospitals; Humans; Male; Multivariate Analysis; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Respiratory Tract Diseases; Retrospective Studies; Severity of Illness Index; Treatment Outcome

A total of 18,656 Enterobacteriaceae and 4,175 Pseudomonas aeruginosa were consecutively collected from 85 US hospitals and tested for susceptibility by broth microdilution methods in a central monitoring laboratory (JMI Laboratories). The antimicrobial susceptibility and frequency of key resistance phenotypes were assessed and stratified by infection type as follows: bloodstream (BSI; 3,434 isolates; 15.0%), pneumonia (6,439; 28.2%), skin and skin structure (SSSI; 4,134; 18.1%), intra-abdominal (IAI; 951; 4.2%), and urinary tract (UTI; 7,873; 34.5%). Ceftazidime-avibactam was active against 99.9% to 100.0% of Enterobacteriaceae and 97.0% (pneumonia) to 99.4% (UTI) of P. aeruginosa isolates. Susceptibility rates were consistently lower for β-lactams, such as ceftazidime (82.3% vs. 87.1-90.8%), piperacillin-tazobactam (87.5% vs. 90.2-95.6%), and meropenem (96.8% vs. 98.4-99.4%) among Enterobacteriaceae from pneumonia compared to other infection types. Susceptibility to gentamicin was also generally lower among isolates from pneumonia, whereas susceptibility to levofloxacin and colistin were lowest among BSI and SSSI isolates, respectively. The occurrence of multidrug-resistance (MDR; 8.2% overall), extensively drug-resistance (XDR; 1.1% overall), and carbapenem-resistant Enterobacteriaceae (CRE; 1.3% overall) phenotypes were markedly higher among isolates from patients with pneumonia compared to other infection types. Among P. aeruginosa, susceptibility rates for ceftazidime, piperacillin-tazobactam, and gentamicin were lowest among isolates from pneumonia, whereas susceptibility to meropenem was similar among isolates from BSI, pneumonia, and IAI (77.3-77.9%), and susceptibility to levofloxacin was markedly lower among UTI isolates (67.1%). The frequencies of P. aeruginosa isolates with MDR and XDR phenotypes were highest among isolates from patients with pneumonia.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Ceftazidime; Colistin; Cross Infection; Drug Combinations; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections; Thienamycins; United States

Piperacillin, in combination with tazobactam, is frequently used in infants for treating nosocomial infections, although safety data in this population are limited. Electronic health record (EHR) data can be used to evaluate drug safety in infants, but measures of drug exposure are lacking.. To relate simulated piperacillin exposure with adverse events (AEs) in infants using EHR data, we identified infants discharged from 333 neonatal intensive care units managed by the Pediatrix Medical Group between 1997 and 2012. Using a previously published population pharmacokinetic model in the target population, we simulated piperacillin steady state area under the concentration versus time curve from zero to τ (AUCss,0-τ) and steady state maximal drug concentration (Cmaxss). Next, we used multivariable logistic regression to evaluate the association between simulated AUCss,0-τ and Cmaxss with clinical AEs (seizure and rash) and laboratory AEs controlling for gestational age. The odds ratios (95% confidence intervals) comparing the third versus the first tertiles for AUCss,0-τ and Cmaxss were reported.. We identified 746 infants with a median (interquartile range) gestational age of 30 weeks (26-33) and postnatal age of 11 days (6-25). The median (interquartile range) piperacillin dose was 225 mg/kg/d (176-300). No significant associations were found between simulated piperacillin exposure (AUCss,0-τ and Cmaxss) and clinical and laboratory AEs.. We found no associations between predicted piperacillin exposures and the occurrence of AEs. This study confirms the feasibility of using population pharmacokinetics and EHR to relate drug exposure with safety.

Topics: Anti-Bacterial Agents; Area Under Curve; Cross Infection; Electronic Health Records; Female; Humans; Infant; Infant, Newborn; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies

Acinetobacter pittii is a nosocomial pathogen rarely involved in community-acquired infections. We report for the first time that A. pittii can be responsible for cavitary community-acquired pneumonia and study its virulence, and discuss its pathogenesis and treatment options.. A 45-year-old woman with a history of smoking and systemic lupus was admitted to Nimes University Hospital (France) with coughing and sputum lasting for three weeks. Thoracic CT scanner showed cavitary pneumonia. Broncho-alveolar lavage cultures found community-acquired Acinetobacter calcoaceticus-baumannii complex. The clinical outcome was favourable after twenty-one days of antimicrobial treatment by piperacillin/tazobactam and amikacin then cefepime. Multilocus sequence typing (MLST) analyses identified an A. pittii ST249. Despite the atypical clinical presentation with an unexpected partial destruction of lung parenchyma, we found very low virulence potential of the A. pittii strain with nematode killing assays and biofilm formation test. The median time required to kill 50% of the nematodes was 7 ± 0.3 days for A. pittii ST249, 7 ± 0.2 days for A. baumanii NAB ST2 and 8 ± 0.2 days for E. coli OP50, (p > 0,05). A. pittii ST249 showed significantly slower biofilm formation than A. baumanii NAB ST2: BFI = 8.83 ± 0.59 vs 3.93 ± 0.27 at 2 h (p < 0.0001), BFI = 6.3 ± 0.17 vs 1.87 ± 0.12 at 3 h (p < 0.0001) and BFI = 3.67 ± 0.41 vs 1.7 ± 0.06 after 4 h of incubation (p < 0.01).. Community-acquired A. pittii should be considered as possible cause of sub-acute cavitary pneumonia particularly in a smoking and/or immunocompromised patient despite its low virulence potential.

Topics: Acinetobacter; Acinetobacter Infections; Amikacin; Animals; Caenorhabditis elegans; Community-Acquired Infections; Cross Infection; Female; France; Humans; Middle Aged; Multilocus Sequence Typing; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Virulence

Anti-infective shortages represent a growing threat to optimum management of infected patients and alter the institutional selective pressure against hospital-acquired infections (HAIs). The objective of this analysis was to assess the impact of a shortage of piperacillin/tazobactam (TZP) on overall antibacterial use and HAI rates at an academic institution.. Antimicrobial use and infection data were extracted from TheraDoc Clinical Surveillance Software (Premier, Inc.) for adult patients and were stratified as pre-shortage (October-December 2014) and post-shortage (February-April 2015). Paediatric and emergency department use were excluded. Antimicrobial use was reported as percent change and defined daily doses (DDD)/1000 patient-days (PD). Pre- and post-shortage vancomycin-resistant enterococci (VRE) and Clostridium difficile-associated diarrhoea (CDAD) rates were normalised to 1000 PD/month.. Total use of target antimicrobials remained constant before and after TZP shortage (990.29 vs. 957.77). Total TZP use fell 95.2% (81.1 vs. 3.9). Total meropenem use rose 96.0% (42.3 vs. 82.9) after the shortage, driven by a 125.4% increase in use for non-ICU patients. Cefepime and ceftazidime use rose 97.9% (28.2 vs. 55.8) and 94.2% (1.6 vs 3.0), respectively. Cefepime use in non-ICU patients rose 223.2%. Fluoroquinolone consumption did not differ between periods. CDAD rates decreased (-21.8%), whilst VRE rates doubled during the shortage (0.6 vs. 1.3 infections/1000 PD/month).. Whilst overall antimicrobial use appeared steady, the TZP shortage resulted in increased use of multiple other antimicrobials. The doubling of VRE rates is concerning and illustrates the need for increased antimicrobial stewardship vigilance and education in response to shifting prescribing patterns during shortages.

Topics: Academic Medical Centers; Adult; Anti-Bacterial Agents; Antimicrobial Stewardship; Clostridioides difficile; Cross Infection; Drug Resistance, Bacterial; Drug Utilization; Enterococcus; Female; Humans; Male; Piperacillin, Tazobactam Drug Combination

The prevalence and antibiotic resistance of Acinetobacter spp. from fifty samples of meat (chicken, turkey, beef and pork) were evaluated. Acinetobacter spp. was recovered from all samples and the clonal relatedness of 223 isolates identified to belong to the genus Acinetobacter was established by PFGE. A high genetic diversity was observed and 166 isolates from different samples, 141 representing different PFGE profiles, were further identified to the species level by rpoB gene sequencing. Thirteen distinct Acinetobacter species were identified among 156 isolates. The remaining ten isolates may represent three putatively novel species since rpoB sequence homologies with type strains of all available described Acinetobacter species, were <95%. The most common species was Acinetobacter guillouiae with a prevalence of 34.9%. However 18.7% of the strains belong to the Acinetobacter baumannii group (n=31) which include the species Acinetobacter baumannii (n=7), Acinetobacter pittii (n=12), Acinetobacter seifertii (n=8) and Acinetobacter nosocomialis (n=4) that are the species most frequently associated with nosocomial infections worldwide. In general, strains were resistant to some of the antimicrobials most frequently used to treat Acinetobacter infections such as piperacillin-tazobactam (64.9% of strains resistant), ceftazidime (43.5%), ciprofloxacin (42.9%), as well as to colistin (41.7%) and polymyxin B (35.1%), the last-resort drugs to treat infections caused by multidrug-resistant Acinetobacter. The percentage of resistant strains to trimethoprim-sulfamethoxazole, tetracycline, aminoglycosides (amikacin and tobramycin) and ampicillin-sulbactam was >10% (23.2%, 23.2%, 14.3%, 12.5%, 12.5%, respectively). However, resistances to meropenem, imipenem and minocycline were only sporadically observed (8.3%, 1.2% and 1.2%, respectively). Overall, 51.2% of the strains were considered as multidrug-resistant (MDR) and 9.6% as extensively drug-resistant (XDR). The prevalence of MDR strains within the A. baumannii group (38.7%) was lower than the prevalence within the others species identified (54.1%). Therefore, food of animal origin may be a vehicle of spread Acinetobacter strains resistant to several antibiotics in the community and in the hospital setting environment. This may led to nosocomial and community-acquired infections in susceptible individuals.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Ampicillin; Animals; Anti-Bacterial Agents; Cattle; Ceftazidime; Chickens; Ciprofloxacin; Cross Infection; DNA-Directed RNA Polymerases; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prevalence; Red Meat; Sulbactam; Swine; Trimethoprim, Sulfamethoxazole 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

The study was to establish a population pharmacokinetic (PPK) model of piperacillin (PIP) and tazobactam (TAZ) that explain pharmacokinetic variability and to propose optimized dosage regimens in patients with nosocomial infections.. In total, 310 PIP and 280 TAZ concentration-time points were collected at steady state over multiple dosing intervals from 50 patients who received PIP/TAZ infused within 30 min or over 3 h. Drug analysis was performed by high-performance liquid chromatography (HPLC). Nonlinear mixed effects modeling was employed to develop PPK model and 1000 Monte Carlo simulation was used to predict the probability of target attainment (PTA) with a target time of non-protein-bound concentration above MIC > 50 % of the dosing interval.. A model with one-compartment model had the best predictive performance for the PPK model. The population estimates of PIP were 13.8 L/h (31.1 %) for clearance (CL) and 21.7 L (38 %) for volume of distribution (V). The population estimates of TAZ were 9.3 L/h (29.1 %) for CL and 16 L (35.3 %) for V. Influence of creatinine clearance (CLcr) and body weight were identified as important covariates for PIP/TAZ CL and V, respectively. A 30-min infusion of 4 g every 6 h achieved robust (≥90 %) PTAs for MIC ≤ 16 mg/L. As an alternative mode of administration, a 3-h infusion of 4 g every 6 h achieved robust PTAs for Pseudomonas aeruginosa and Klebsiella pneumoniae.. Prolonged infusions achieved better PTAs compared with shorter infusions at similar daily doses. This benefit was most pronounced for MICs between 16 and 40 mg/L.

Topics: Anti-Bacterial Agents; Body Weight; Cross Infection; Female; Humans; Infusions, Intravenous; Male; Microbial Sensitivity Tests; Middle Aged; Models, Biological; Monte Carlo Method; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Tazobactam

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

Fluoroquinolone resistance in both Gram-positive and Gram-negative bacteria has increased with the widespread use of fluoroquinolones. Fluoroquinolone resistance in Gram-negative bacilli has been widely studied, though staphylococci and enterococci are also notably resistant. Enterococci being the second most common cause of healthcare-associated urinary tract infections (UTIs) fluoroquinolones are often the drug of choice. This study was undertaken to assess the risk factors associated with fluoroquinolone-resistant enterococcal UTI in a tertiary level health facility in north India.. A total of 365 patients with UTI caused by enterococci were studied over a period of two years. Patients with ciprofloxacin-resistant and susceptible UTI were considered as cases and controls, respectively. Resistance profile of the isolates against common antibiotics was studied by minimum inhibitory concentration (MIC) determination. Mechanisms for fluoroquinolone resistance was studied by efflux pump inhibitor activity and multiplex PCR targeting the qnr genes.. A total of 204 (55.89%) cases and 161 (44.1%) controls were identified. The fluoroquinolone-resistant isolates were significantly resistant to ampicillin, high strength aminoglycosides and vancomycin. The majority (78%) of the resistant isolates showed efflux pump activity. Treatment in indoor locations, presence of urinary catheters and pregnancy along with recent exposure to antibiotics especially fluoroquinolones, third generation cephalosporins and piperacillin-tazobactam were identified as independent risk factors.. Our results showed that fluoroquinolone resistance in enterococcal UTI was largely associated with indoor usage of antibiotics and use of indwelling devices. Knowledge of risk factors is important to curb this emergence of resistance.

Topics: Ciprofloxacin; Cross Infection; Drug Resistance, Bacterial; Enterococcus; Female; Fluoroquinolones; Hospitals, University; Humans; India; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pregnancy; Risk Factors; Tertiary Care Centers; Urinary Tract Infections

The relationship between fluoroquinolone resistance in Escherichia coli isolates causing nosocomial infection and hospital antibiotic consumption were investigated. Restriction of levofloxacin use was implemented to control the incidence of fluoroquinolone-resistant E coli in the hospital.. The study was conducted from January 2004 to December 2010. Antimicrobial agent consumption was obtained from the pharmacy computer system and presented as the defined daily doses per 1000 patient-days every 6 months. The incidence of fluoroquinolone-resistant E coli isolates causing nosocomial infections was obtained from the Department of Infection Control every 6 months. An antimicrobial stewardship program, restricting levofloxacain use, was implemented in July 2007.. The incidence of fluoroquinolone-resistant E coli causing nosocomial infections was significantly correlated with fluoroquinolone usage (p = 0.005), but not with the use of third- or fourth-generation cephalosporins, piperacillin-tazobactam, or carbapenems. Parenteral (p = 0.002), oral (p = 0.018), and total levofloxacin (p = 0.001) use were significantly correlated with the extent of fluoroquinolone resistance. With a reduction of levofloxacin use, a decrease of the incidence of fluoroquinolone resistance in E coli isolates was observed.. There is a significant correlation between levofloxacin use and the incidence of nosocomial fluoroquinolone-resistant E coli isolates. The incidence of fluoroquinolone-resistant E coli could be reduced by limiting levofloxacin consumption.

Topics: Anti-Bacterial Agents; Carbapenems; Cephalosporins; Cross Infection; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Humans; Levofloxacin; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

Stenotrophomonas maltophilia is a bacterial pathogen associated with health-care associated infections, particularly in immunocompromised patients. Members of the fluoroquinolone drug class are frequently used to treat S. maltophilia infection; however, S. maltophilia resistance to fluoroquinolones, especially levofloxacin, has been increasing.. We sought to identify risk factors associated with levofloxacin resistance using a case-control study. We examined sputum from 76 S. maltophilia-positive patients admitted to our hospital between January 1, 2010 and June 30, 2011. Case groups were defined as patients who had S. maltophilia infections resistant to levofloxacin, and control groups were defined as patients who had S. maltophilia infections susceptible to levofloxacin treatment. Patient information including demographics, previous antibiotic use, and other traits were recorded. In addition, S. maltophilia isolates from patient sputum were assessed for antibiotic resistance as well as for the presence of genes associated with drug resistance.. Previous antibiotic treatment with first- or second-generation cephalosporin was found more often in the levofloxacin-susceptible group; by contrast, previous piperacillin/tazobactam treatment occurred more often in the levofloxacin-resistant group. Three genes associated with drug resistance, including SmeA, SmeD, and SpgM were not significantly different between these groups.. Piperacillin/tazobactam treatment is associated with subsequent isolation of levofloxacin-resistant S. maltophilia from the respiratory tract.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Case-Control Studies; Cross Infection; Drug Resistance, Bacterial; Drug Utilization; Female; Gram-Negative Bacterial Infections; Hospitals; Humans; Levofloxacin; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Respiratory Tract Infections; Risk Factors; Sputum; Stenotrophomonas maltophilia

Although Morganella morganii causes a variety of clinical infections, there are limited studies on M. morganii bacteremia after the year 2000. A total of 109 patients with M. morganii bacteremia at a medical center in Taiwan from 2003 to 2012 were studied. Among them, 30.3 % had polymicrobial bacteremia and 75.2 % had community-acquired infection. The most common underlying diseases were hypertension (62.4 %) and diabetes mellitus (38.5 %). The urinary tract (41.3 %) was the major portal of entry, followed by the hepatobiliary tract (27.5 %), skin and soft tissue (21.1 %), and primary bacteremia (10.1 %). Susceptibility testing of M. morganii isolates showed ubiquitous resistance to first-generation cephalosporins and ampicillin-clavulanate; resistance rates to gentamicin, piperacillin-tazobactam, and ciprofloxacin were 30.3 %, 1.8 %, and 10.1 %, respectively. Overall, the 14-day mortality was 14.7 %. Univariate analysis revealed that elevated blood urea nitrogen (BUN) values [p = 0.0137, odds ratio (OR) 5.26], intensive care unit (ICU) admission (p = 0.011, OR 4.4), and higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (p < 0.001, OR 1.62) were significantly associated with mortality. The APACHE II score remained the only significant risk factor for mortality in multivariate analysis (p = 0.0012, OR 1.55). In conclusion, M. morganii bacteremia patients were mostly elderly, with one or more comorbidities. Most of the patients had community-acquired infection via the urinary and hepatobiliary tracts. Furthermore, prognosis can be predicted according to disease severity measured by the APACHE II score.

Topics: Age Factors; Aged; Aged, 80 and over; Ampicillin; Anti-Bacterial Agents; Bacteremia; Cephalosporins; Community-Acquired Infections; Cross Infection; Drug Resistance, Bacterial; Enterobacteriaceae Infections; Female; Gentamicins; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Morganella morganii; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Risk Factors; Taiwan

We determined the prevalence of ESBL Enterobacteriaceae in urinary tract infections among inpatients, identified risk factors of acquisition, and evaluated the effectiveness of alternatives to carbapenems.. The clinical, microbiological, and therapeutic data as well as the outcomes were recorded for all ESBL-E positive urine samples for three months.. Thirty-one (4%) of the 762 Enterobacteriaceae positive cultures were ESBL producers. The predisposing conditions for being infected with those strains were: immunodepression (61%), recent hospitalization (52%), recent antibiotic therapy (52%), and urinary catheterization (61%). 19% of infections were community acquired. The seven cases of acute pyelonephritis and five of prostatitis were treated with piperacillin-tazobactam (5), fluoroquinolones (4), ceftazidime (2), or carbapenems (only 1) after specialized advice. Four (33%) patients relapsed at week 10: three were immunodepressed and three presented with bacteremia.. Alternatives to carbapenems (especially piperacillin-tazobactam) seem to be a good option for non-bacteremic UTI in immunocompetent patients.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Catheter-Related Infections; Ceftazidime; Community-Acquired Infections; Cross Infection; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Fluoroquinolones; Hospitalization; Hospitals, University; Humans; Immunocompromised Host; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prevalence; Prostatitis; Recurrence; Retrospective Studies; Risk Factors; Urinary Tract Infections; Young Adult

Carbapenems have an overall broad antibacterial spectrum and should be protected against from the acquisition of drug resistance. The clinical advantages of carbapenem in cases of pneumonia have not been certified and the need for antipseudomonal antimicrobial agents to treat healthcare-associated pneumonia (HCAP) remains controversial. We introduced an antimicrobial stewardship program for carbapenem and tazobactam/piperacillin use and investigated the effects of this program on the clinical outcomes of 591 pneumonia cases that did not require intensive care unit management, mechanical ventilation or treatment with vasopressor agents [221 patients with community-acquired pneumonia (CAP) and 370 patients with HCAP]. Compared with the pre-intervention period, age, comorbidities and the severity and etiology of pneumonia did not differ during the intervention period. Carbapenems were rarely used during the intervention period in cases of pneumonia (CAP: 12% vs. 1%, HCAP: 13% vs. 1%), while antipseudomonal beta-lactam use was reduced from 33% to 8% among cases with HCAP. This reduction in the rate of carbapenem administration did not have an impact on the prognosis in the cases of CAP, and the in-hospital mortality was lower among the patients with HCAP during the intervention period (15% vs. 5%, p = 0.013). The causes of death in the cases of HCAP were not directly related to pneumonia during the intervention period. The current study shows that carbapenem use can be avoided in cases of CAP or HCAP that are not in a critical condition. The frequent use of antipseudomonal beta-lactams does not improve the clinical outcomes of HCAP.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Community-Acquired Infections; Cross Infection; Female; Hospital Mortality; Humans; Male; Middle Aged; Needs Assessment; Organizational Policy; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Prognosis; Pseudomonas Infections

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

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

The purpose of this study was to review central line-associated blood stream infection (CLABSI) data from a surgical trauma intensive care unit to better understand patient risk factors, pathogens, and treatment interventions. We performed a retrospective review of all surgical ICU patients who met the Centers for Disease Control definition for Gram-negative CLABSI from 2006 through 2013. Demographics, pathogens, interventions, and outcomes were evaluated. A total of 40 patients were included with an average age of 49.9 ± 19 years and 72.5 per cent male. The average length of central venous line (CVL) was 11 ± 5.9 days with average time from line placement to positive culture 9.4 ± 6.8 days. Most common organisms were Enterobacter species (37.5%) with 17.8 per cent of all cultured organisms considered multidrug resistant. Piperacillin-tazobactam (67.5%) was the most commonly used antibiotic. Overall mortality rate was 22.5 per cent. A total of 11 patients who developed a recurrence did so at 10.7 ± 8 days and were similar to those without recurrence. Predominant pathogens associated with surgical trauma intensive care unit CLABSI in this study are different from those Gram-negative bacteria associated with published studies in the general hospital population. Further investigation into risk factors for infection and relapse is important to minimize such consequences. Understanding appropriate line placement and use as well as clarifying optimal duration of therapy is integral in improving outcomes.

Topics: Adult; Aged; Bacteremia; Catheter-Related Infections; Catheterization, Central Venous; Cohort Studies; Comprehension; Cross Infection; Female; Follow-Up Studies; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Hospital Mortality; Humans; Incidence; Intensive Care Units; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Risk Assessment; Survival Rate; Tertiary Care Centers; Treatment Outcome; Urban Population; Virginia

Topics: Cross Infection; Environmental Exposure; Equipment Contamination; Fatal Outcome; Female; Humans; Italy; Legionella pneumophila; Legionnaires' Disease; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

OprD loss and hyperexpression of AmpC, MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM were evaluated among 120 Pseudomonas aeruginosa isolates collected during 2012 in U.S. hospitals and selected based on ceftazidime MIC values (1 to >32 μg/ml). AmpC derepression (10-fold greater than that with the control) and OprD loss (decreased/no band) were the most prevalent resistance mechanisms: 47.5 and 45.8% of the isolates were considered positive, respectively. Elevated expression of the efflux pumps MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM was observed in 32.5, 8.3, 0.0, and 28.4% of the isolates, respectively. A total of 21 different combinations of resistance mechanisms were noted, and the most prevalent included AmpC derepression with OprD loss with and without efflux hyperexpression (38 and 10 isolates, respectively). A total of 26 isolates had no changes in the resistance mechanisms tested and had lower MIC values for all β-lactams or β-lactam/β-lactamase inhibitor combinations analyzed. OprD loss had a strong correlation with elevated MIC results for imipenem and meropenem (median MIC values of 8 and 4 μg/ml, respectively), with all combinations displaying OprD loss also displaying elevated median MIC values for these carbapenems (4 to >8 μg/ml). AmpC expression levels were greater in isolates displaying elevated cefepime, ceftazidime, or piperacillin-tazobactam MIC values (≥4, ≥4, and ≥16 μg/ml, respectively). Isolates displaying derepressed AmpC had ceftolozane-tazobactam MIC values ranging from 1 to 16 μg/ml. No strong correlation was noticed with MIC values for this β-lactam/β-lactamase inhibitor combination and OprD loss or hyperexpression of efflux systems. Two KPC-producing isolates were detected among 16 isolates displaying ceftolozane-tazobactam MIC values of ≥8 μg/ml.

Topics: Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Cefepime; Ceftazidime; Cephalosporins; Cross Infection; Gene Expression Regulation, Bacterial; Humans; Membrane Transport Proteins; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Porins; Pseudomonas aeruginosa; Pseudomonas Infections

This study aimed to clarify the efficacy, safety, and pharmacokinetics of piperacillin–tazobactam (PIPC– TAZ) in late elderly Japanese patients. This is the first antimicrobial pilot study in late elderly patients with nursing and healthcare associated pneumonia. After PIPC–TAZ administration, PIPC concentrations in plasma were measured chromatographically and the pharmacokinetic parameters were estimated. Efficacy, safety, and bacteriological evaluations were also carried out. The mean age was 85.0 years old and most of the patients were late elderly. Chest X-rays, body temperature, white blood cell count, and C reactive protein all improved significantly, and a high efficacy ratio of 90.9% was observed. Serious nephrotoxicity was observed in 4 cases (18.2%) after administration of PIPC–TAZ. Creatinine clearance (meanS.D.) measured before PIPC–TAZ therapy was significantly lower in the nephrotoxicity group (32.54.4 mL/min) than in the non-nephrotoxicity group (46.116.7 mL/min), although the ages were not different between the 2 groups. In the pharmacokinetic parameters for PIPC, total clearance was slightly lower in the nephrotoxicity group than in the non-nephrotoxicity group. However, no significant difference was observed in plasma PIPC levels between the 2 groups. In patients with renal impairment, especially with a creatinine clearance of <40 mL/ min, renal impairment was found to be an influencing factor for severe nephrotoxicity following PIPC–TAZ administration. In conclusion, the results suggest that physicians should pay close attention in order to avoid possible toxicity, and that deliberate administration planning and careful follow-up are required in late elderly patients with comprised organ dysfunction.

Topics: Aged; Aged, 80 and over; Aging; Anti-Bacterial Agents; Asian People; Cross Infection; Female; Humans; Kidney Diseases; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial

Nosocomial pneumonia remains an important cause of mortality and morbidity worldwide. Surveillance programs play an important role in the identification of common etiologic agents and local patterns of antimicrobial resistance.. In this study we determined the frequency and antimicrobial susceptibility of pathogens isolated from patients with nosocomial pneumonia during 2009 to 2011.. A total of 642 bacteria were isolated from 516 suspected samples. Acinetobacter baumannii (21.1%, n = 136), was the commonest isolated pathogen followed by Pseudomonas aeruginosa (17.4%, n = 112), Staphylococcus aureus (15.8%, n = 102) and enterococci (8.4% n = 54). The most effective therapeutic agents against A. baumannii were polymyxin B (95.5% susceptible), ceftriaxone/tazobactam (72% susceptible) and levofloxacin (52.9% susceptible). Polymixin B (89.2% susceptible), ceftriaxone/tazobactam (89.2% susceptible) and piperacillin-tazobactam (80.3% susceptible) were found to be the most active agents against P. aeruginosa. Extended-spectrum beta-lactamases were detected among isolates of K. pneumoniae (45.4%) and E. coli (20.3%). Overall, the prevalence of methicillin-resistant S. aureus and vancomycin resistant enterococci were 80.4% and 40.7% respectively. Linezolid was found to be the most active antibiotic against these pathogens. The etiology of 50% of the nosocomial infection cases was polymicrobial.. The combination of ceftriaxone/tazobactam seems to be beneficial agent against multidrug-resistant Gram-negative bacilli isolated form respiratory tract infections. The results of our study can be used for guiding appropriate empiric therapy in this geographic region.

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Ceftriaxone; Cross Infection; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Hospitals; Humans; Iran; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Polymyxin B; Prevalence; Pseudomonas aeruginosa; Respiratory Tract Infections; Sputum; Staphylococcus aureus

Pneumonia is associated with an extremely high mortality rate in patients of late elderly age. Piperacillin/tazobactam and carbapenems are drugs of first choice for hospitalized patients with potentially resistant bacteria. We compared the efficacy and safety of piperacillin/tazobactam and biapenem. Among elderly patients with nursing- and healthcare-associated pneumonia, we extracted 53 patients treated with piperacillin/tazobactam and 53 patients treated with biapenem who were matched for sex, age, and severity of pneumonia. The average age was more than 80 years; most of the patients were middle- to oldest old in age. Although clinical efficacy was equally good, patients in the piperacillin/tazobactam group achieved significantly faster improvements on chest X-ray and body temperature on day 7. However, in the piperacillin/tazobactam group, nephrotoxicity frequently led to a need for a reduction in the dose or complete discontinuation of treatment. The average age of patients who developed significant nephrotoxicity was high, at 83.2 years. The biapenem group exhibited significantly better continuation of treatment than the piperacillin/tazobactam group. Toxicity profiles were different between the two groups. Hepatic toxicity was significantly higher in the biapenem group, whereas nephrotoxicity was significantly more common in the piperacillin/tazobactam group. Rate of decrease in bacteria was equally good between the two groups. Providing careful follow-up and conducting more detailed examinations, including studies to determine optimal dose and timing of administration, are necessary for the treatment of late elderly patients with numerous underlying diseases and potential organ dysfunctions.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Cross Infection; Female; Hospitalization; Humans; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Retrospective Studies; Sputum; Thienamycins

Nosocomial infection caused by carbapenem-resistant Acinetobacter baumannii is a worldwide problem and treatment options remain controversial. This study investigated the in vitro effect of various antibiotic combinations against carbapenem-resistant A. baumannii strains.. Antibiotic susceptibility of A. baumannii strains was analysed. In vitro synergistic efficacy of colistin combined with tigecycline, cefoperazone/sulbactam or piperacillin/tazobactam was tested against carbapenem-resistant A. baumannii strains. Synergy studies were performed using an eplisometer test-strip method.. Of the 50 carbapenem-resistant A. baumannii strains tested, 96% were susceptible to colistin and 64% were susceptible to tigecycline. Colistin-tigecycline, colistin-cefoperazone/sulbactam and colistin-piperacillin/tazobactam combinations were found to have synergistic effects against six (12%), two (4%), and one (2%), respectively, of the strains tested.. Colistin combined with tigecycline, cefoperazone/sulbactam or piperacillin/tazobactam revealed synergistic effects in some carbapenem-resistant A. baumannii strains. These results, together with the shortage of treatment options and the risk of developing resistance to colistin, suggest that clinicians should use colistin combined with other antibiotics or β-lactamase inhibitors when treating carbapenem-resistant A. baumannii infection.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamase Inhibitors; Carbapenems; Cefoperazone; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Microbial Sensitivity Tests; Minocycline; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sulbactam; Tigecycline

The pharmacokinetics-pharmacodynamics (PK-PD) breakpoint of piperacillin/tazobactam (PIPC/TAZ) for hospital-acquired pneumonia (HAP) and Pseudomonas aeruginosa-induced bacteremia is controversial, since the susceptibility of P. aeruginosa to PIPC/TAZ is known to be lower than that set by the Clinical Laboratory Standards Institute (CLSI), ≤64 mg/L. The association between MIC levels and bacterial eradication after various PIPC/TAZ treatments was investigated. In all, 61 and 17 Japanese patients from the microbiology laboratory database with HAP and P. aeruginosa-induced bacteremia, respectively, who were treated with PIPC/TAZ (4.5 g, b.i.d., t.i.d., or q.i.d.) between 2008 and 2009 were retrospectively analyzed. Pertinent clinical data were retrieved from medical records. The MIC level was determined using the microdilution method. Appropriate empirical therapy with PIPC/TAZ was selected for all patients within 24 h of positive culture results. The microbiological effect after treatment was used to determine the efficacy of each PIPC/TAZ administration method. In PIPC/TAZ-treated HAP patients (4.5 g, t.i.d.), the microbiological efficacy was 93.3% (28/30) when the MIC was ≤16 mg/L, while it was 50.0 (5/9) and 0% (0/3) with MICs of 32 (p < 0.05) and 64 mg/L, respectively. In PIPC/TAZ-treated bacteremia patients (4.5 g, t.i.d. or q.i.d.), the microbiological efficacy was 100% (11/11) when the MIC was <16 mg/L, while it was 33.3 (1/3) and 0% (0/3) with MICs of 32 (p < 0.05) and ≥64 mg/L, respectively. The present CLSI susceptibility breakpoints do not necessarily predict clinical outcomes. The appropriateness evaluation of the current CLSI resistance breakpoint of PIPC/TAZ and the PK-PD breakpoint determination warrant further studies.

Topics: Anti-Bacterial Agents; Bacteremia; Cross Infection; Humans; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies

Six years after initiating a monthly antibiotic cycling protocol in the surgical intensive care unit (SICU), we retrospectively reviewed antibiogram-derived sensitivities of predominant gram-negative pathogens before and after antibiotic cycling. We also examined susceptibility patterns in the medical intensive care unit (MICU) where antibiotic cycling is not practiced.. Antibiotic cycling protocol was implemented in the SICU starting in 2003, with monthly rotation of piperacillin/tazobactam, imipenem/cilastin, and ceftazidime. SICU antibiogram data from positive clinical cultures for years 2000 and 2002 were included in the pre-cycling period, and those from 2004 to 2009 in the cycling period.. Profiles of SICU pseudomonal isolates before (n = 116) and after (n = 205) implementing antibiotic cycling showed statistically significant improvements in susceptibility to ceftazidime (66% versus 81%; P = 0.003) and piperacillin/tazobactam (75% versus 85%; P = 0.021), while susceptibility to imipenem remained unaltered (70% in each case; P = 0.989). Susceptibility of E. coli isolates to piperacillin/tazobactam improved significantly (46% versus 83%; P < 0.0005), trend analysis showing this improvement to persist over the study period (P = 0.025). Similar findings were not observed in the MICU. Review of 2004-2009 antibiotic prescription practices showed monthly heterogeneity in the SICU, and a 2-fold higher prescribing of piperacillin/tazobactam in the MICU (P < 0.0001).. Six years into antibiotic cycling, we found either steady or improved susceptibilities of clinically relevant gram-negative organisms in the SICU. How much of this effect is from cycling is unknown, but the antibiotic heterogeneity provided by this practice justifies its ongoing use.

Topics: Anti-Bacterial Agents; Ceftazidime; Cilastatin; Cilastatin, Imipenem Drug Combination; Critical Care; Cross Infection; Drug Combinations; Drug Resistance, Bacterial; Enterobacter cloacae; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Infections; Humans; Imipenem; Infection Control; Klebsiella Infections; Klebsiella pneumoniae; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Surgical Wound Infection

While extended infusions of piperacillin-tazobactam (TZP) are increasingly used in practice, the effect of infusion on the pharmacokinetic (PK) profile of TZP has not been widely assessed. To assess its effect on the pharmacokinetic profile of TZP, seven serum samples were collected from 11 hospitalized patients who received 3.375 g TZP intravenously for 4 h every 8 h. Population pharmacokinetic models were fit to the PK data utilizing first-order, Michaelis-Menten (MM), and parallel first-order/MM clearance. A population PK model with first-order clearance was fit to the tazobactam PK data. Monte Carlo simulations (MCSs) were used to determine the most effective administration schedule to ensure that free piperacillin concentrations were above the MIC for at least 50% of the dosing interval (50% fT>MIC) and to quantify the extent of the nonlinear clearance. The model incorporating parallel linear/MM clearance best fit the piperacillin PK data. The MCSs demonstrated that approximately 50% of the administered piperacillin is cleared by the nonlinear clearance mechanism. The results of the MCSs also revealed that more intensive TZP extended infusion dosing schemes (3.375 to 4.5 g intravenously [3-h infusion] every 6 h) than those commonly used in clinical practice were needed to maximize the 50% fT>MIC for MICs of ≥8 mg/liter. This study suggests that extended infusion of TZP is the most effective method of administration for patients with nosocomial infections. Due to the hyperclearance nature of the hospitalized patient populations studied, more intensive TZP dosing regimens may be needed to maximize fT>MIC in certain hospitalized populations.

Topics: Adult; Anti-Bacterial Agents; Cross Infection; Drug Administration Schedule; Female; Hospitalization; Humans; Infusions, Intravenous; Male; Metabolic Clearance Rate; Microbial Sensitivity Tests; Middle Aged; Monte Carlo Method; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Young Adult

Antimicrobial resistance among microorganisms is a global concern. In 2003, a nationwide antibiotic restriction program (NARP) was released in Turkey. In this study we evaluated the effect of NARP on antibiotic consumption, antimicrobial resistance, and cost.. The data obtained from all of the four university hospitals, and one referral tertiary-care educational state hospital in Ankara. Antimicrobial resistance profiles of 14,233 selected microorganisms all grown in blood cultures and antibiotic consumption from 2001 to 2005 were analyzed retrospectively.. A negative correlation was observed between the ceftriaxone consumption and the prevalence of ceftriaxone resistant E.coli and Klebsiella spp. (rho:-0.395, p:0.332 and rho:-0.627, p:0.037, respectively). The decreased usage of carbapenems was correlated with decreased carbapenems-resistant Pseudomonas spp. and Acinetobacter spp (rho:0.155, p:0.712 and rho:0.180, p:0.668, respectively for imipenem). Methicillin resistance rates of S.aureus were decreased from 44% to 41%. After two years of NARP 5,389,155.82 USD saving occurred.. NARP is effective in lowering the costs and antibiotic resistance.

Topics: Acinetobacter; Anti-Bacterial Agents; Cefepime; Ceftazidime; Ceftriaxone; Cephalosporins; Cost Savings; Cross Infection; Drug Costs; Drug Prescriptions; Drug Resistance, Bacterial; Drug Utilization; Escherichia; Health Policy; Hospitals; Humans; Imipenem; Klebsiella; Meropenem; Methicillin Resistance; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas; Staphylococcus aureus; Teicoplanin; Thienamycins; Turkey; Vancomycin

Sphingomonas paucimobilis, is a yellow-pigmented, aerobic, non fermentative, gram negative motile bacillus. S. paucimobilis which is widely found in nature and hospital environments rarely cause serious or life threatening infections. In this report, a case of hospital acquired bloodstream infection due to S. paucimobilis in a patient with Down syndrome who was on treatment for presumed pneumonia is presented. A one year-old child patient who was a known case of Down syndrome and had previously experienced cardiac surgery was hospitalized and treated for pneumonia. On the 12th day of hospitalization, blood cultures were taken because of a high body temperature. One of the blood cultures was positive for gram-negative rods. After 48 hour of incubation, the sub-cultures on blood agar medium yielded pure growth of a yellow, non-fermentative, gram-negative, rod-shaped bacterium. The microorganism was positive for oxidase, and esculin hydrolysis, while negative for urea and nitrate reduction, citrate utilisation and motility. The isolate had been identified as S. paucimobilis by using Vitek 2 system. The antibiotic susceptibility test was also performed with the same system and the strain was found to be susceptible to piperacillin-tazobactam and other antibiotics. Treatment with intravenous piperacilin-tazobactam (150 mg/kg/day) was initiated. He responded well to the treatment and was discharged after 10 days. This case is reported to emphasize that S. paucimobilis should be kept in mind as a nosocomial infectious agent in patients with Down syndrome and immunosuppressive patients and the infections should be treated according to the sensitivity test results.

Topics: Bacteremia; Cross Infection; Down Syndrome; Gram-Negative Bacterial Infections; Humans; Infant; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia; Sphingomonas

This study examined the effect of various levels of renal impairment on the probability of achieving free drug concentrations that exceed the MIC for 50% of the dosing interval (50% fT > MIC) for traditional and extended-infusion piperacillin-tazobactam (TZP) dosing strategies. It also identified optimal renal dosage adjustments for traditional and extended-infusion dosing schemes that yielded probability of target attainment (PTA) and exposure profiles that were isometric to those of the parent regimens. Data from 105 patients were analyzed using the population pharmacokinetic modeling program BigNPAG. To assess the effect of creatinine clearance (CL(CR)) on overall clearance, TZP clearance was made proportional to the estimated CL(CR). A Monte Carlo simulation (9,999 subjects) was performed for the traditional dosing scheme (4.5 g infused during 30 min every 6 h) and the extended-infusion TZP dosing scheme (3.375 g infused during 4 h every 8 h). The fraction of simulated subjects who achieved 50% fT > MIC was calculated for the range of piperacillin MICs from 0.25 to 32 mg/liter and stratified by CL(CR). The traditional TZP regimen displayed the greatest variability in PTA across MIC values, especially for MIC values exceeding 4 mg/liter, when stratified by CL(CR). In contrast, the PTA for the extended-infusion TZP regimen exceeded >or=80% for MIC values of or=32 mg/liter irrespective of the CL(CR). The CL(CR) adjustments for traditional and extended-infusion TZP dosing regimens should be considered at a CL(CR) of

Topics: Area Under Curve; Bayes Theorem; Cross Infection; Drug Combinations; Female; Hospitalization; Humans; Infusions, Intravenous; Kidney; Kidney Function Tests; Male; Microbial Sensitivity Tests; Middle Aged; Models, Statistical; Monte Carlo Method; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Pneumococcal; Reproducibility of Results; Tazobactam; United States; United States Food and Drug Administration

Initial treatment of nosocomial pneumonia (NP), including ventilator-associated pneumonia (VAP), is usually empirical. The use of a broad-spectrum antibiotic regimen to treat NP-VAP that is active against suspected multidrug-resistant pathogens maximizes the likelihood of a favorable outcome. In a post hoc analysis of pooled data from 2 prospective, randomized, open-label, phase 3 NP-VAP trials, doripenem, a new broad-spectrum carbapenem with antipseudomonal activity, demonstrated noninferiority to standard comparator regimens (imipenem and piperacillin-tazobactam) with regard to clinical and microbiological outcomes. In subgroup analyses, doripenem continued to show noninferiority to the comparator drugs in achieving clinical and microbiological cures in populations at high risk of multidrug-resistant infection, such as patients with late-onset VAP (defined as patients who develop VAP >5 days after intubation) or those with NP-VAP caused by Pseudomonas aeruginosa or complicated by bacteremia. Overall, the clinical data indicate that doripenem has the potential to be an important option in the treatment of NP, including VAP.

Topics: Carbapenems; Cross Infection; Doripenem; Humans; Imipenem; Infusions, Intravenous; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Ventilator-Associated

The MICs of imipenem, meropenem, piperacillin-tazobactam, cefotaxime, polymixin B and tigecycline against 80 isolates of Acintobacter baumanii from 6 hospitals were determined. A multiplex-PCR was used to detect the genes encoding carbapenemases. Field Inversion Gel Electrophoresis (FIGE) was then used to investigate the genetic relationships among the carbapenem-resistant isolates. Only 7 isolates were resistant to polymixin B and tigecycline (MIC = 16). All isolates were positive for at least 2 carbapenemase genes. At least 10 distinct clones were detected by FIGE. A dominant pattern designated as pulsotype A consisting of 23 isolates was detected from 4 hospitals. The majority of isolates in this pulsotype had a bla(OXA-51/23-like) and bla(OXA-51/24-like) carbapenemase genes and cultured from the patients at burns and ICU. The pan drug resistant isolates belonged to different FIGE patterns. Nosocomial infections with different clones of Acintobacter baumanii occur at Tehran hospitals. However, inter-hospital transmission with certain pulsotypes is likely.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Cefotaxime; Cross Infection; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Genes, Bacterial; Hospitals; Humans; Imipenem; Iran; Meropenem; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Thienamycins

Meticillin-resistant Staphylococcus aureus (MRSA) is a very significant agent of recalcitrant healthcare-associated infections. A major risk of acquiring such infections is thought to be modulated by the use of particular antimicrobial therapies. The aim of this research was to evaluate prospectively the impact of using either ciprofloxacin or Tazocin (piperacillin+tazobactam) on the incidence of MRSA in an Intensive Care Unit (ICU). The 1-year (2 x 6 months) cross-over study was carried out in a medium-sized (426 beds) teaching hospital. During the first 6-month period, ciprofloxacin was used as the first-line broad-spectrum antibiotic therapy of choice. During the second 6-month period, Tazocin was used as first-line therapy. The incidence of hospital-acquired MRSA (i.e. colonised and/or infected) and rates of compliance of the ICU healthcare workers to optimal hand hygiene practices were recorded throughout the study. The study observed no statistically significant differences (P = 0.1) between MRSA incidence rates in the ICU during the ciprofloxacin (4.4/1000 bed-days) or Tazocin (11.4/1000 bed-days) arms of the study. Interestingly, observing healthcare workers' hand hygiene practices throughout the entire study showed that healthcare workers adhered to these practices 59.2% of the time during the ciprofloxacin arm and 66.0% during the Tazocin arm. The low incidence rates within the unit demonstrated the importance of infection control in limiting the spread of MRSA despite the extensive use of antibiotics in a high-risk setting.

Topics: Anti-Bacterial Agents; beta-Lactamase Inhibitors; Ciprofloxacin; Cross Infection; Data Interpretation, Statistical; Drug Combinations; Electrophoresis, Gel, Pulsed-Field; Hand Disinfection; Hygiene; Intensive Care Units; Methicillin-Resistant Staphylococcus aureus; Penicillanic Acid; Personnel, Hospital; Piperacillin; Piperacillin, Tazobactam Drug Combination; Staphylococcal Infections; Tazobactam

The aim of this study was to determine the risk factors for nosocomial infections of imipenem-resistant Pseudomonas aeruginosa (IRPA). A prospective case-control study was performed at a tertiary care hospital in Ankara from January to December 2004. The patients with nosocomial P. aeruginosa infection were included in the study. The features of the patients with IRPA infections were compared to those with imipenem-sensitive P. aeruginosa (ISPA) infections. Only the first isolation of P. aeruginosa was considered. Nosocomial infections were defined according to Center for Disease Control (CDC) criteria. IRPA was isolated from 75 (44.1%) patients, and ISPA was isolated from 95 (55.9%) patients during the study period. IRPA were most frequently isolated from endotracheal aspirate (19%) cultures (p=0.048), whereas ISPA were most frequently isolated from urine (28%) cultures (p=0.023). In multivariate analysis, a longer duration of hospital stay until P. aeruginosa isolation (odds ratio [OR], 1.027; 95% confidence interval [CI], 1.002-1.054, p=0.034), arterial catheter administration (OR, 2.508; 95% CI, 1.062-5.920, p=0.036), vancomycin (OR, 2.882; 95% CI, 1.130-7.349, p=0.027), piperacillin-tazobactam (OR, 6.425; 95% CI, 2.187-18.875, p=0.001), and imipenem (OR, 3.580; 95% CI, 1.252-10.245, p=0.017) treatment within the 14 days before isolation of IRPA were independently associated with imipenem resistance. It was concluded that treatment with imipenem, vancomycin and piperacillin-tazobactam were major risk factors for IRPA infections in hospitalized patients. The nosocomial occurrence of IRPA was also strongly related to the duration of hospital stay, arterial catheter administration.

Topics: Adult; Aged; Anti-Bacterial Agents; Case-Control Studies; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Humans; Imipenem; Length of Stay; Male; Microbial Sensitivity Tests; Middle Aged; Multivariate Analysis; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Risk Factors; Vancomycin

A pharmacodynamic model was used to generate supportive data comparing tigecycline with other broad-spectrum agents against pathogens implicated in hospital-acquired pneumonia (HAP). A 5000 patient Monte Carlo simulation determined the probability of target attainment (PTA) of tigecycline (+/- ceftazidime) compared with imipenem, levofloxacin, and piperacillin/tazobactam (+/- vancomycin). PTA was calculated over MICs of current Gram-positive and Gram-negative bacteria collected from worldwide surveillance and weighted by the expected prevalence of these pathogens causing HAP. For monotherapy, the weighted PTA was imipenem (78.2%), piperacillin/tazobactam (73.3%), tigecycline (62.9%), and levofloxacin (62.5%). By pathogen PTA was greatest for tigecycline against Gram-positives, and ceftazidime or imipenem against Gram-negatives. Combination therapy increased PTA to 88.6%, 85.5%, 80.6%, and 69.8% for tigecycline, imipenem, piperacillin/tazobactam, and levofloxacin, respectively. Based on contemporary resistance data, tigecycline plus ceftazidime is predicted to achieve its pharmacodynamic targets similarly to combination therapy with imipenem plus vancomycin for the treatment of patients with HAP.

Topics: Anti-Bacterial Agents; Cross Infection; Humans; Imipenem; Levofloxacin; Microbial Sensitivity Tests; Minocycline; Models, Biological; Monte Carlo Method; Ofloxacin; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia; Tigecycline

Piperacillin-tazobactam is frequently used to treat Pseudomonas aeruginosa infections in critically ill patients. In an effort to improve clinical outcomes, an extended-infusion dosing scheme for piperacillin-tazobactam therapy was devised using a Monte Carlo simulation and was adopted into clinical practice at Albany Medical Center (Albany, New York). This study evaluates the clinical implications of extended infusion of piperacillin-tazobactam therapy for critically ill patients with P. aeruginosa infection.. We performed a cohort study of patients who received piperacillin-tazobactam therapy for a P. aeruginosa infection that was susceptible to piperacillin-tazobactam during the period January 2000-June 2004. Prior to February 2002, all patients received intermittent infusions of piperacillin-tazobactam (3.375 g intravenously for 30 min every 4 or 6 h); after this time, all patients received extended infusions of piperacillin-tazobactam (3.375 g intravenously for 4 h every 8 h). Data on demographic characteristics, disease severity, and microbiology were collected, and outcomes were compared between groups.. A total of 194 patients comprised the 2 study groups: 102 patients received extended infusions of piperacillin-tazobactam, and 92 patients received intermittent infusions of piperacillin-tazobactam. No differences in baseline clinical characteristics were noted between the 2 groups. Among patients with Acute Physiological and Chronic Health Evaluation-II scores > or =17, 14-day mortality rate was significantly lower among patients who received extended-infusion therapy than among patients who received intermittent-infusion therapy (12.2% vs. 31.6%, respectively; P=.04), and median duration of hospital stay after collection of samples for culture was significantly shorter for patients who received extended-infusion therapy than for patients who received intermittent-infusion therapy (21 days vs. 38 days; P=.02).Conclusions. These results indicate that extended-infusion piperacillin-tazobactam therapy is a suitable alternative to intermittent-infusion piperacillin-tazobactam therapy, and they strongly suggest that improved outcomes may be realized by administering extended-infusion piperacillin-tazobactam therapy to critically ill patients with P. aeruginosa infection.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; APACHE; beta-Lactams; Cohort Studies; Critical Illness; Cross Infection; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Male; Microbial Sensitivity Tests; Middle Aged; Models, Biological; Monte Carlo Method; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas Infections; Retrospective Studies

The aim of this study was to determine the frequency of PER-1 type extended-spectrum beta-lactamase (ESBL) in nosocomial Pseudomonas aeruginosa strains isolated in Hacettepe University Adult Hospital. Sixty-seven non-duplicate P. aeruginosa isolates from patients with nosocomial infections between January 2002 and December 2004 were included in the study. The isolates were identified at species-level by Sceptor (Becton Dickinson, USA) system, and all the strains were stored at -80 degrees C until further testing. Polymerase chain reaction (PCR) was performed for the detection of (bla)PER-1 genes, and PFGE analysis was used to investigate their genetic relatedness. The antimicrobial susceptibilities of the PER-1 positive isolates were determined by Etest (AB Biodisk, Solna, Sweden) method. According to the results of PCR, 22.7% (15/67) of the isolates were positive for PER-1 enzyme. Those 15 (bla)PER-1 positive isolates showed eight different PFGE patterns, indicating the presence of multiple clones. Of the PER-1 positive P. aeruginosa isolates, nine were resistant to imipenem/meropenem, and 11 were resistant to piperacillin-tazobactam and tobramycin. The epidemiological investigation of multidrug resistant P. aeruginosa should give important clues for the initial empirical therapy, especially in certain geographic locations where ESBL-producing P. aeruginosa strains seemed to be highly prevalent.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cross Infection; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Humans; Imipenem; Meropenem; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Polymerase Chain Reaction; Pseudomonas aeruginosa; Pseudomonas Infections; Thienamycins; Tobramycin

We report the case of a 52-year-old man, ASA 3-4, malnourished, heavy smoker and drinker at the stage of chronic obstructive pulmonary disease and cirrhosis. The postoperative course of a cervical cancer surgery was complicated by a pneumonia with fatal outcome in the intensive care unit. Taking into account the patient's history and surgical requirements, this nosocomial infection did not appear easily preventable. The multiple risk factors and the few preventive measures usable were analyzed. In this context, the media and legal trend to make the doctors responsible for the nosocomial infections should be revised.

Topics: Alcoholism; Amoxicillin-Potassium Clavulanate Combination; Antibiotic Prophylaxis; Carcinoma, Squamous Cell; Ciprofloxacin; Cross Infection; Disease Susceptibility; Fatal Outcome; Humans; Iatrogenic Disease; Immunocompromised Host; Liver Cirrhosis, Alcoholic; Male; Malnutrition; Malpractice; Middle Aged; Mouth; Neck Dissection; Neoplasm Recurrence, Local; Oxygen; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia; Postoperative Complications; Pulmonary Disease, Chronic Obstructive; Risk Factors; Smoking; Tongue Neoplasms

States in 2002 on antimicrobial prescribing and associated rates of vancomycin-resistant enterococci (VRE) and Clostridium difficile infections.Design. Retrospective chart review.Setting. University-affiliated medical center. Measurements and Main Results. Microbiologic reports, patient demographics, and antimicrobial utilization were evaluated for patients admitted 6 months before the shortage (March 1-August 31, 2001) and for 6 months during the shortage (March 1-August 31, 2002). Significant increases in usage of alternative mu-lactamase inhibitor combinations, cefepime, levofloxacin, vancomycin, clindamycin, and metronidazole were observed during the shortage; in contrast, a significant decrease in the use of ceftriaxone took place. No change in the rate of VRE infection was observed from before to during the piperacillin-tazobactam shortage. However, a paradoxical 47% decrease in the rate of C. difficile colitis was documented during the shortage. Subsequent multivariate analyses suggested the reduced use of ceftriaxone and increased use of levofloxacin, but not the reduced use of piperacillin-tazobactam, correlated with the decreased rate of C. difficile infections.. The piperacillin-tazobactam shortage was associated with significant changes in antimicrobial prescribing, which resulted in a significant reduction in the rate of C. difficile but not VRE infections.

Topics: Anti-Bacterial Agents; California; Clostridioides difficile; Cross Infection; Drug Prescriptions; Drug Utilization; Enterococcus; Enterocolitis, Pseudomembranous; Gram-Positive Bacterial Infections; Humans; Length of Stay; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; United States; Vancomycin Resistance

Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli, particularly those producing CTX-M types of ESBL, are emerging pathogens. Bacteremia caused by these organisms represents a clinical challenge, because the organisms are frequently resistant to the antimicrobials recommended for treatment of patients with suspected E. coli sepsis.. A cohort study was performed that included all episodes of bloodstream infection due to ESBL-producing E. coli during the period from January 2001 through March 2005. Data on predisposing factors, clinical presentation, and outcome were collected. ESBLs were characterized using isoelectric focusing, polymerase chain reaction, and sequencing.. Forty-three episodes (8.8% of cases of bacteremia due to E. coli) were included; 70% of the isolates produced a CTX-M type of ESBL. The most frequent origins of infection were the urinary (46%) and biliary tracts (21%). Acquisition was nosocomial in 21 cases (49%), health care associated in 14 cases (32%), and strictly community acquired in 8 cases (19%). Thirty-eight percent and 25% of patients had obstructive diseases of the urinary and biliary tracts, respectively, and 38% had recently received antimicrobials. Nine patients (21%) died. Compared with beta-lactam/beta-lactamase-inhibitor and carbapenem-based regimens, empirical therapy with cephalosporins or fluoroquinolones was associated with a higher mortality rate (9% vs. 35%; P=.05) and needed to be changed more frequently (24% vs. 78%; P=.001).. ESBL-producing E. coli is a significant cause of bloodstream infection in hospitalized and nonhospitalized patients in the context of the emergence of CTX-M enzymes. Empirical treatment of sepsis potentially caused by E. coli may need to be reconsidered in areas where such ESBL-producing isolates are present.

Topics: Adult; Aged; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Cephalosporins; Cohort Studies; Community-Acquired Infections; Cross Infection; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Fluoroquinolones; Humans; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

To compare the probability of achieving specific pharmacodynamic exposures of commonly used intravenous antibiotics for the empirical treatment of nosocomial pneumonia against those pathogens most commonly implicated in the disease.. Ten thousand-subject Monte Carlo simulation.. Research center.. None.. Pharmacodynamic analysis was conducted for the following antimicrobials at standard doses: meropenem, imipenem-cilastatin, ceftazidime, cefepime, piperacillin/tazobactam, and ciprofloxacin. Prevalence of causative pathogens was based on the 2000 SENTRY Antimicrobial Surveillance Study, and minimum inhibitory concentration (MIC) values were obtained using the 2003 US MYSTIC database. The probabilities of each drug and dosing regimen in achieving pharmacodynamic targets were calculated. Bactericidal targets were defined as 40% T>MIC for the carbapenems, 50% T>MIC for other beta-lactams, and an area under the curve (AUC)/MIC ratio of 125 for ciprofloxacin. A sensitivity analysis was performed using two alternate models to determine the impact of varying pathogen prevalence on target attainment.. Meropenem and imipenem provided high probabilities of achieving their bactericidal target of 40% T>MIC, with target attainments of 98% for all regimens. At the bactericidal end point of 50% T>MIC, cefepime 2 g every 8 hrs displayed the highest target attainment at 99.9%, followed by cefepime 2 g every 12 hrs, ceftazidime 2 g every 8 hrs, piperacillin/tazobactam 4.5 g every 6 hrs and 3.375 g every 6 hrs, cefepime 1 g every 12 hrs, and ceftazidime 1 g every 8 hrs with target attainments of 95.0%, 92.5%, 92.3%, 91.3%, 90.3%, and 67.9%, respectively. Ciprofloxacin presented the lowest probability of achieving its bactericidal target of an AUC/MIC ratio of 125, with target attainments of 54.7% and 12.0% when given as 400 mg every 8 hrs and 400 mg every 12 hrs, respectively.. Meropenem, imipenem, cefepime, ceftazidime (2 g every 8 hrs), and piperacillin/tazobactam have high probabilities of achieving adequate pharmacodynamic exposures when given for the empirical treatment of nosocomial pneumonia in the absence of methicillin-resistant S. aureus. Ceftazidime 1g every 8 hrs and ciprofloxacin produce low target attainment rates and will not likely result in high clinical success rates when given as monotherapy.

Topics: Anti-Bacterial Agents; Cefepime; Ceftazidime; Cephalosporins; Ciprofloxacin; Cross Infection; Dose-Response Relationship, Drug; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Monte Carlo Method; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Thienamycins

The incidence of infections caused by Candida glabrata and Candida krusei, which are generally more resistant to fluconazole than Candida albicans, is increasing in hospitalized patients. However, the extent to which prior exposure to specific antimicrobial agents increases the risk of subsequent C. glabrata or C. krusei candidemia has not been closely studied. A retrospective case-case-control study was performed at a university hospital. From 1998 to 2003, 60 patients were identified with hospital-acquired non-C. albicans candidemia (C. glabrata or C. krusei; case group 1). For comparison, 68 patients with C. albicans candidemia (case group 2) and a common control group of 121 patients without candidemia were studied. Models were adjusted for demographic and clinical risk factors, and the risk for candidemia associated with exposure to specific antimicrobial agents was assessed. After adjusting for both nonantimicrobial risk factors and receipt of other antimicrobial agents, piperacillin-tazobactam (odds ratio [OR], 4.15; 95% confidence interval [CI], 1.04 to 16.50) and vancomycin (OR, 6.48; CI, 2.20 to 19.13) were significant risk factors for C. glabrata or C. krusei candidemia. For C. albicans candidemia, no specific antibiotics remained a significant risk after adjusted analysis. Prior fluconazole use was not significantly associated with either C. albicans or non-C. albicans (C. glabrata or C. krusei) candidemia. In this single-center study, exposure to antibacterial agents, specifically vancomycin or piperacillin-tazobactam, but not fluconazole, was associated with subsequent hospital-acquired C. glabrata or C. krusei candidemia. Further studies are needed to prospectively analyze specific antimicrobial risks for nosocomial candidemia across multiple hospital centers.

Topics: Anti-Infective Agents; Candida glabrata; Candidiasis; Case-Control Studies; Cross Infection; Female; Fluconazole; Fungemia; Humans; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Risk Factors; Vancomycin

Currently, the use of beta-lactamase inhibitors in combination with beta-lactam antibiotics represents an effective measure to combat a specific resistance mechanism of beta-lactamase producing organisms. Knowledge about the susceptibility profile of bacteria to different combination agents available is essential to guide appropriate treatment of severe infections in hospitalized patients. The present study compares the in vitro activity of three commercially available beta-lactam/beta-lactamase inhibitor combinations (piperacillin/tazobactam, cefoperazone/sulbactam, ticarcillin/clavulanic acid) against beta-lactamase producing gram negative bacteria in a tertiary care hospital in north India.. A total of 9004 consecutively isolated extended spectrum beta-lactamase (ESBL) producing gram negative bacteria isolated from various clinical samples from patients admitted to the All India Institute of Medical Sciences, New Delhi, from September 2003 to August 2004 were included in the study. These isolates were screened for ESBL production by the inhibitor based test recommended by the National Committee for Clinical Laboratory Standards (NCCLS). Antibiotic susceptibility testing was carried out by disc diffusion method as per NCCLS guidelines.. Of the 9004 isolates tested, 3232 (35.89%) were sensitive and 568 (6.31%) were resistant to all three combination agents, and rest 5204 (57.80%) were resistant to at least one of the combinations. Susceptibility to piperacillin/tazobactam, cefoperazone/sulbactam, and ticarcillin/clavulanic acid was 81.37, 76.06 and 45.48 per cent respectively. Piperacillin/tazobactam exhibited significantly (P<0.05) greater antimicrobial activity against Pseudomonas spp., Escherichia coli and Klebsiella spp. compared to cefoperazone/sulbactam.. Overall piperacillin/tazobactam was observed to be the best combination agent followed by cefoperazone/sulbactam in our setting. This difference in activities of these combination agents needs to be evaluated further by ascertaining their efficacy in clinical studies.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamase Inhibitors; Cefoperazone; Clavulanic Acids; Cross Infection; Gram-Negative Bacteria; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sulbactam; Ticarcillin

We have previously observed a significant reduction of ceftriaxone resistance in Proteus mirabilis associated with an increase in the use of cefepime, along with a decrease in the consumption of broad-spectrum cephalosporins (CEP). However, we did not observe such a reduction with Klebsiella pneumoniae. Therefore, we sought to determine whether replacement of CEP by piperacillin-tazobactam might be useful in reducing sustained high rates of CEP resistance by this organism. We used a 6-month "before and after model"; during the second (intervention) period, most prescriptions of CEP were changed to piperacillin-tazobactam at the pharmacy. No additional barrier precautions were undertaken. During intervention, consumption of ceftazidime decreased from 17.73 to 1.14 defined daily doses (DDD) per 1,000 patient-days (P < 0.0001), whereas that of piperacillin-tazobactam increased from 0 to 30.57 DDD per 1,000 patient-days (P < 0.0001). The levels of resistance to CEP by K. pneumoniae and P. mirabilis decreased from 68.4 and 57.9% to 37.5 and 29.4%, respectively (P < 0.05). We conclude that replacement of ceftazidime by piperacillin-tazobactam might be a suitable strategy to decrease endemic CEP resistance by K. pneumoniae and P. mirabilis, even where there are high bacterial resistance rates and irrespective of any additional precautions for controlling nosocomial infection.

Topics: Anti-Bacterial Agents; Argentina; Cephalosporin Resistance; Cephalosporins; Cross Infection; Drug Prescriptions; Drug Utilization; Humans; Infection Control; Klebsiella Infections; Klebsiella pneumoniae; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

To determine the steady-state plasma and epithelial lining fluid (ELF) concentrations of piperacillin/tazobactam (P/T) administered to critically ill patients with severe bacterial pneumonia.. Prospective, open-label study.. An intensive care unit and research ward in a university hospital.. Ten adult patients with severe nosocomial bacterial pneumonia on mechanical ventilation.. All subjects received a 30-min intravenous infusion of P/T 4 g/0.5 g every 8 h. The steady-state plasma and ELF concentrations of P/T were determined by high-performance liquid chromatography.. The mean+/-SD steady-state plasma trough, peak, and intermediate concentrations were 8.5+/-4.6 microg/ml, 55.9+/-21.6 microg/ml, and 24.0+/-13.8 microg/ml for piperacillin, and 2.1+/-1.0 microg/ml, 4.8+/-2.1 microg/ml, and 2.4+/-1.2 microg/ml for tazobactam, respectively. The mean+/-SD steady-state intermediate ELF concentrations were 13.6+/-9.4 microg/ml for piperacillin and 2.1+/-1.1 microg/ml for tazobactam, respectively, showing a mean percentage penetration of piperacillin and tazobactam into ELF of 56.8% and 91.3 %, respectively, with a P/T ratio of 6.5:1.. Our results show that during the treatment of severe nosocomial pneumonia, a regimen of P/T 4 g/0.5 g every 8 h might provide insufficient concentrations into lung tissue to exceed the MIC of many causative pathogens. This suggests that higher doses of P/T should be administered in order to maximize the antibiotic concentration at the site of infection, or that a second antimicrobial agent should be used in association.

Topics: Cross Infection; Epithelial Cells; Female; Humans; Intensive Care Units; Lung; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Prospective Studies; Respiration, Artificial

The prevalence of vancomycin-resistant enterococci (VRE) is increasing, despite infection control measures. Limited data link ticarcillin-clavulanate to higher VRE prevalence.. Active surveillance for VRE was conducted before and after a formulary switch from ticarcillin-clavulanate to piperacillin-tazobactam. Rectal swabs were obtained serially in 863 adult patients admitted to intensive care units (ICUs) between November 1, 2000 and September 30, 2004.. In the postswitch period, 38 of 497 (7.6%) patients acquired VRE versus 42 of 366 (11.5%) patients in the preswitch period. Survival analysis showed an overall hazard ratio (HR) of .68 postswitch versus preswitch ( P = .07), with the greatest change in the surgical ICU (HR = .17, P = .006). Multivariate analysis showed an overall HR = .51 ( P = .004). Hospital-wide, nonstool VRE clinical cultures fell from 39 (.58/1000 patient days) in the 10-month preswitch period to 27 (.33/1000 patient days) in the 12-month postswitch period. Infection control practices and use of other antibiotics remained stable.. VRE acquisition appeared to decrease in association with a formulary change from ticarcillin-clavulanate to piperacillin-tazobactam.

Topics: Anti-Bacterial Agents; Carrier State; Clavulanic Acids; Cross Infection; Enterococcus faecium; Female; Formularies, Hospital as Topic; Gastrointestinal Tract; Humans; Intensive Care Units; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Risk Factors; Ticarcillin; Time Factors; Vancomycin Resistance

Topics: Cross Infection; Drug Therapy, Combination; Humans; Intensive Care Units; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia; Respiration, Artificial; Treatment Outcome

To describe the variation in clinical practice strategies for the treatment of suspected ventilator-associated pneumonia (VAP) in a population of critically ill patients, and to determine whether initial empiric treatment with certain antibiotics, monotherapy vs combination antibiotic therapy, or appropriate vs inappropriate antibiotic therapy is associated with survival, length of hospital stay, or days free of antibiotics.. Prospective, observational cohort study.. Medical-surgical ICUs of two university-affiliated tertiary medical centers.. Between May 1, 1998, and August 1, 2000, we screened 7,030 ICU patients and identified 156 patients with clinically suspected VAP. Patients were followed up until death or discharge from the hospital.. The mean age was 62 years, mean APACHE (acute physiology and chronic health evaluation) II score was 14, and mortality was 34%. Combination antibiotic therapy was used in 53% of patients. Piperacillin-tazobactam, fluoroquinolones, vancomycin, cephalosporins, and aminoglycosides were the most commonly employed antibiotics. Initial empiric antibiotics were deemed appropriate in 92% of patients. The predominant organisms isolated from respiratory secretions included Pseudomonas aeruginosa and Staphylococcus aureus. Patients had lower in-hospital mortality rates if their initial treatment regimen included an antipseudomonal penicillin plus beta-lactamase inhibitor (hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.21 to 0.80; p = 0.009). There was also a strong trend toward reduced mortality rates in patients treated with aminoglycosides (HR, 0.43; 95% CI, 0.16 to 1.11; p = 0.08). Specific antibiotic therapy was not associated with length of hospital stay or days free of antibiotics. Outcomes were similar for patients treated with monotherapy vs combination therapy, and for patients who received initial appropriate vs inappropriate therapy.. Patients with clinically suspected VAP who receive initial empiric therapy with antipseudomonal penicillins plus beta-lactamase inhibitors, and possibly aminoglycosides, have lower in-hospital mortality rates when compared with those who are not treated with these antibiotics. These agents should be considered for the initial empiric therapy of VAP.

Topics: Aminoglycosides; Anti-Bacterial Agents; Anti-Infective Agents; California; Cross Infection; Drug Therapy, Combination; Female; Fluoroquinolones; Humans; Intensive Care Units; Male; Middle Aged; Multivariate Analysis; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia; Proportional Hazards Models; Prospective Studies; Respiration, Artificial; Survival Rate; Treatment Outcome

We investigated the antimicrobial activity of piperacillin-tazobactam versus piperacillin-sulbactam against common nosocomial pathogens (n = 565) isolated from intensive care patients. For Gram-positive bacteria, antimicrobial susceptibilities to the two piperacillin-beta-lactamase inhibitor combinations were almost identical. For Gram-negative bacteria, piperacillin-tazobactam exhibited greater activity against Escherichia coli and Proteus vulgaris than piperacillin-sulbactam. Both combinations, however, were equally effective against the other Enterobacteriaceae and Pseudomonas aeruginosa isolates. Piperacillin-sulbactam exhibited better antimicrobial activity against Acinetobacter baumannii. Our findings might prove important for the appropriate choice of antibiotic therapy with beta-lactam-beta-lactamase inhibitor combinations.

Topics: Anti-Bacterial Agents; Cross Infection; Drug Therapy, Combination; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sulbactam

To evaluate the effect of a change in antibiotic protocol on pathogens that cause neonatal sepsis.. Suspected sepsis was treated with amikacin together with ceftazidime in 1995-1998 and piperacillin/tazobactam in 1999-2002.. The annual rate for Klebsiella sepsis fell from 2.5 to 0.45 cases per 1000 admission days (p = 0.0001) between the two periods studied.. The change from ceftazidime to piperacillin/tazobactam is associated with a decrease in the incidence of Klebsiella sepsis.

Topics: Anti-Bacterial Agents; Ceftazidime; Cross Infection; Drug Resistance, Multiple, Bacterial; Humans; Infant, Newborn; Infection Control; Israel; Klebsiella Infections; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

This study was designed to test whether rotation of antibiotics can reduce colonization with resistant Gram-negative bacilli in a neonatal intensive care unit (NICU).. A monthly rotation of gentamicin, piperacillin-tazobactam, and ceftazidime was compared with unrestricted antibiotic use in side-by-side NICU populations (rotation team vs control team). Pharyngeal and rectal samples were obtained 3 times a week and tested for Gram-negative bacilli resistant to each of the rotation antibiotics. Pulsed-field gel electrophoresis analysis determined the numbers of genetically discordant resistant organisms on each team. The association between colonization with a resistant bacillus (the primary outcome) and team assignment was tested.. A total of 1062 infants were studied during a 1-year period. A total of 10.7% infants on the rotation team versus 7.7% on the control team were colonized with a resistant bacillus. No interteam differences were distinguishable when the numbers of genetically discordant resistant organisms were normalized to the total number of team admissions. The incidence of nosocomial infection and mortality also were similar across teams.. These data indicate that rotation of parenteral antibiotics according to the applied protocol has no detectable effect in decreasing the reservoir of resistant Gram-negative bacilli in a tertiary-care NICU.

Topics: Anti-Bacterial Agents; Ceftazidime; Cross Infection; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Gentamicins; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Microbial Sensitivity Tests; Penicillanic Acid; Pharynx; Piperacillin; Piperacillin, Tazobactam Drug Combination; Rectum

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

Pseudomonas aeruginosa is a major problem as a multiresistant nosocomial pathogen, especially in burns and other immunocompromised patients in our hospital. The present prospective study, conducted between June 1996 and December 1997, was aimed at determining the extent of its resistance against highly active antipseudomonal drugs, such as carbapenems (imipenem and meropenem) and ureidopenicillin with beta-lactamase inhibitor (piperacillin/tazobactam); existence of any cross resistance or difference in susceptibility between imipenem and meropenem; and to compare the activity of piperacillin/tazobactam with the two carbapenems against P. aeruginosa. Of the 357 P. aeruginosa isolates tested from 188 patients 37 (10.4%) were resistant to imipenem, 21 (5.9%) to meropenem and 50 (14%) to piperacillin/tazobactam. Cross resistance between the two carbapenems was observed in 5.9% of the isolates. Sixteen (43%) of the imipenem-resistant isolates were susceptible to meropenem but the reverse was observed in none. Amongst the 50 piperacillin/tazobactam-resistant isolates cross resistance with the two carbapenems was observed in 18 (36%) and in 9 (18%) only with imipenem; 23 (46%) were susceptible to both. Our results indicate that P. aeruginosa is least resistant to meropenem followed by imipenem and piperacillin/tazobactam. Cross resistance between the carbapenems and between carbapenems and piperacillin/tazobactam was found. The study further suggests that burns, cardiac-neuro-pediatric surgical, cancer and transplant patients are more susceptible to acquiring infection due to multiresistant P. aeruginosa than other types of patients and common infection sites were wounds, respiratory tract, urine, blood and intravascular lines.

Topics: Carbapenems; Cross Infection; Drug Resistance, Multiple; Drug Therapy, Combination; Humans; Incidence; Microbial Sensitivity Tests; Penicillanic Acid; Penicillin Resistance; Penicillins; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Pseudomonas aeruginosa; Risk Factors

Burn patients are at high risk for nosocomial infections due to multiresistant bacteria, a large proportion of which are gram-negative. Tazobactam, a potent inhibitor of beta-lactamases, extends the spectrum of piperacillin to include many beta-lactamase producing bacteria. Consequently, it was decided to evaluate the activity of piperacillin/tazobactam in comparison with that of eight other antibiotics that are usually used for therapy against gram-negative bacterial infections in our burn unit. All consecutive gram-negative isolates from wounds, blood, respiratory tract, urine etc. from burn patients considered to be clinically significant were tested for their susceptibility to piperacillin/tazobactam, piperacillin, ceftazidime, cefotaxime, ceftriaxone, ciprofloxacin, gentamicin, amikacin and imipenem, determined by disk diffusion test. The zone inhibition was interpreted according to NCCLS recommendations. A total of 948 strains, isolated during the period of July, 1994 to September, 1995, made up of Pseudomonas spp (326), Acinetobacter spp (268) and Enterobacteriaceae (354), were tested. Overall piperacillin/tazobactam showed superior activity over the other antibiotics except for imipenem. Of the 948 isolates, 87% were susceptible to the combination, 56% to the three third generation cephalosporins, 69% to ciprofloxacin, 59% to the aminoglycosides and 97% to imipenem. Piperacillin/tazobactam showed strikingly superior activity over piperacillin alone against Acinetobacter spp followed by Enterobacteriaceae and the least against Pseudomonas. The emergence of Acinetobacter spp as a dominant gram-negative pathogen in burn patients and its high level of resistance against most of the antibiotics tested except piperacillin/tazobactam (87%) and imipenem (100%) were significant in light of the epidemiology of burn infections and treatment. This study suggests that piperacillin/tazobactam holds good promise against gram-negative infections in burn patients.

Topics: Burns; Cross Infection; Drug Therapy, Combination; Gram-Negative Bacteria; Humans; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

Due to increasing frequency of infections caused by pathogens that are resistant to beta-lactam antibiotics, combinations of such antibiotics and beta-lactamase inhibitors were introduced into therapy in last few years. Tazobactam is the most potent beta-lactamase inhibitor. The purpose of the study was to evaluate in vitro susceptibility to piperacillin and piperacillin with tazobactam of 256 isolates cultured from biological samples obtained from 203 patients. The biological materials obtained were as follows: urine (44.9%), post-operative and post-traumatic wound swabs (27.3%), BAL (12.1%), blood (6.6%), drain swabs and other (5.5%). The isolates predominantly found were Escherichia coli (22.3%), Pseudomonas aeruginosa (16.0%), Staphylococcus aureus MSSA (13.7%), Proteus mirabilis (11.7%) and other. There were 95.5% of strains found susceptible to piperacillin with tazobactam and only 4.3% resistant ones. On the other hand, piperacillin only susceptible strains were 59.4% and resistant ones in 40.6%. Great differences in susceptibility to examined antimicrobial agents were observed in Enterobacteriaceae family and Staphylococcus (MSS) genus. There were no differences in susceptibility to piperacillin and tazobactam and piperacillin alone in anaerobic Enterobacteriaceae strains and non-fermenting Gram-negative bacilli.

Topics: beta-Lactamase Inhibitors; Body Fluids; Cross Infection; Drug Resistance, Microbial; Drug Therapy, Combination; Enterobacteriaceae; Gram-Negative Bacteria; Humans; Microbial Sensitivity Tests; Penicillanic Acid; Penicillins; Piperacillin; Piperacillin, Tazobactam Drug Combination; Species Specificity; Tazobactam

The aim of the study was to determine the activity of four beta-lactam antibiotics against nosocomial strains of Gram-positive bacteria. Two antibiotics combined with beta-lactamase inhibitors: timentin (TIC/CLAV) and tazocin (PIP/TZB) and two carbapenems: imipenem and meropenem were applied. The clinical strains were isolated from patients hospitalized in surgical ward of the National Clinical Hospital No 1 in Warsaw. The strains were identified in the automatic ATB system using ID 32 STAPH, API STREP, API CORYNE and API 20 A strips. The susceptibility of isolates to antibacterial agents was determined in the automatic ATB system using ATB STAPH, ATB STREP and ATB ANA strips. The susceptibility of strains to timentin, tazocin, imipenem and meropenem was tested with disc diffusion method. 111 strains of Gram-positive bacteria were cultured. Staphylococci (49) and enterococci (44) dominated among isolated strains. 33 Staphylococcus spp. strains were identified as methicillin-resistant. The obtained results indicate a significant role of Gram-positive cocci (staphylococci and enterococci) in the aetiology of nosocomial infections. Antibiotics combined with beta-lactamase inhibitors and carbapenems demonstrate broad antibacterial spectrum against clinical strains of Gram-positive bacteria except E. faecium strains.

Topics: Anti-Bacterial Agents; beta-Lactamase Inhibitors; Clavulanic Acids; Cross Infection; Drug Resistance, Microbial; Drug Therapy, Combination; Gram-Positive Bacteria; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Species Specificity; Thienamycins; Ticarcillin