piperacillin--tazobactam-drug-combination and Pneumonia--Bacterial

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

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

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

Given the high frequency of acute pulmonary exacerbations due to Pseudomonas aeruginosa in patients with cystic fibrosis (CF), piperacillin/tazobactam is commonly used in empirical regimens. While extended-infusion piperacillin/tazobactam has been employed as one strategy to optimize this agent's pharmacodynamics, this approach has not been well characterized in patients with CF. The objectives of this study were to characterize the pharmacokinetics and pharmacodynamics of extended-infusion piperacillin/tazobactam in adult patients with CF and derive optimized piperacillin/tazobactam dosing recommendations.. Six serum samples were collected from nine adult patients with CF hospitalized for acute pulmonary exacerbations who received 3/0.375 g of piperacillin/tazobactam intravenously for 4 h every 8 h. Population pharmacokinetic models were fitted to the data utilizing first-order, Michaelis-Menten (MM) and parallel first-order/MM clearance. Monte Carlo simulations were performed to determine the probability of target attainment (PTA) for regimens where free piperacillin concentrations were above the MIC for at least 50% of the dosing interval.. The model incorporating MM clearance best described the data. Results of our simulation revealed that piperacillin/tazobactam dosed at 3-4 g for 30 min every 6-8 h led to <90% PTA against MIC values >4 mg/L. More intensive prolonged infusion regimens than are commonly used in practice, such as continuous infusions or 3 h infusions every 6 h, were needed to maximize the PTA for MICs ≥ 8 mg/L.. Intensive prolonged infusion regimens are the best option to ensure optimal exposures against most susceptible isolates in adult patients with CF.

Topics: Adult; Anti-Bacterial Agents; Cystic Fibrosis; Female; Humans; Infusions, Intravenous; Male; Microbial Sensitivity Tests; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Serum; 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

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

The standard mode of administration of piperacillin treatment is by intermittent infusion. However, continuous infusion may be advantageous as beta-lactam antibiotics exhibit time-dependent antibacterial activity. In previous studies, we found a higher rate of clinical cure of ventilator-associated pneumonia (VAP) by continuous infusion rather than intermittent infusion of meropenem and ceftazidime. Therefore, the objective of this historical cohort study was to establish the clinical efficacy of piperacillin/tazobactam (PIP/TAZ) administered by continuous and intermittent infusion in the treatment of VAP in patients without renal failure. Logistic regression analysis showed a higher probability of clinical cure of VAP by continuous compared with intermittent infusion when the microorganism responsible for VAP had a minimum inhibitory concentration (MIC) of 8 microg/mL [8/9 (88.9%) vs. 6/15 (40.0%); odds ratio (OR)=10.79, 95% confidence interval (CI) 1.01-588.24; P=0.049] or 16 microg/mL [7/8 (87.5%) vs. 1/6 (16.7%); OR=22.89, 95% CI 1.19-1880.78; P=0.03]. Thus, administration of PIP/TAZ by continuous infusion may be considered more effective than intermittent infusion for the treatment of VAP caused by Gram-negative bacteria when the MIC of the microorganism responsible for VAP is 8-16 microg/mL in patients without renal failure.

Topics: Aged; Anti-Bacterial Agents; Bacteria; Cohort Studies; Female; Humans; Infusions, Intravenous; Male; Microbial Sensitivity Tests; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Treatment Outcome

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

In a randomized trial conducted in 27 intensive care units, we compared the clinical efficacy and safety of piperacillin-tazobactam (TAZ; 4 g/0.5 g q.i.d.) and of ceftazidime (CAZ; 1 g q.i.d.), both combined with amikacin (7.5 mg/kg b.i.d.), as therapy for ventilator-associated pneumonia (VAP; acquired after > or =48 hours of mechanical ventilation). VAP was diagnosed with use of protected samples and quantitative cultures, and outcome was assessed blindly from treatment. Of 204 patients suspected of having VAP and randomized to a treatment arm of the study, 127 (64%) had bacteriologically confirmed infections, of which 37% were polymicrobial and 32% involved Pseudomonas aeruginosa; 115 patients (51 TAZ and 64 CAZ recipients) remained evaluable as per protocol. Clinical/bacteriologic cure rates (TAZ vs. CAZ, 51% vs. 36%; 95% confidence interval of difference, -0.2% to 30.2%), and 28-day mortality rates (16% vs. 20%) were similar; however, fewer bacteriologic failures occurred with TAZ (33% vs. 51%; P = .05). We conclude that the two regimens were of equivalent clinical efficacy in therapy for confirmed VAP.

Topics: Amikacin; Anti-Bacterial Agents; Ceftazidime; Cephalosporins; Consumer Product Safety; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Population; Treatment Failure; Ventilators, Mechanical

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

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

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

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

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

A 52-year-old female patient was admitted to our clinic with complaints of cough, sputum, fever and fatigue. The patient has been receiving immunosuppressive therapy for thrombocytopenic purpura for 5 years.. Inspiratory crackles were heard on both hemithorax. Oxygen saturation measured with the pulse oximeter was 97%. Chest X-ray showed diffuse reticular opacities that were more prominent in the upper zones of both lungs. WBC counts were 17,600 mm. The patient was hospitalized with suspicion of opportunistic pulmonary infections and cavitary lung disease. After the empirical treatment of intravenous piperacillin-tazobactam and oral clarithromycin, her clinical and radiological findings significantly regressed, and she was discharged with outpatient follow-up.. This is the first example of cavitary pneumonia due to. Una mujer de 52 años llegó a la clínica con tos, esputo, fiebre y fatiga. El paciente estuvo recibiendo terapia inmunosupresora durante 5 años para el tratamiento de la púrpura trombocitopénica.. se escucharon crepitaciones inspiratorias en ambos hemitórax. La saturación de oxígeno fue del 97%. La radiografía de tórax mostró opacidades reticulares difusas que eran más prominentes en las zonas superiores de ambos pulmones. Los recuentos de leucocitos fueron de 17,600 mm. La paciente fue hospitalizado con una sospecha de infección oportunista pulmonar y enfermedad pulmonar cavitaria. Después del tratamiento empírico de piperacilina-tazobactam intravenosa y claritromicina oral, los síntomas y signos retrocedieron significativamente, y fue dada de alta con seguimiento ambulatorio.. este es el primer registro de neumonía cavitaria causado por

Topics: Anti-Bacterial Agents; Clarithromycin; Delftia acidovorans; Female; Gram-Negative Bacterial Infections; Humans; Immunocompromised Host; Lung; Middle Aged; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Tomography, X-Ray Computed

Enterobacter spp. are a common cause of nosocomial pneumonia and treatment can be complicated by AmpC resistance. Carbapenems are the treatment of choice; however, alternatives are needed. Cefepime has been shown to be non-inferior to carbapenems. There are limited data to support the use of piperacillin/tazobactam. The objective of this study was to determine if piperacillin/tazobactam is non-inferior to cefepime or ertapenem for Enterobacter pneumonia treatment.. To compare the rate of clinical cure in patients with Enterobacter pneumonia receiving definitive treatment with piperacillin/tazobactam, cefepime, or ertapenem. Secondary outcomes included hospital mortality, infection-related length of stay, duration of mechanical ventilation, recurrent pneumonia, and resistance.. Retrospective, single-center study.. Of 114 patients included, 59 received definitive treatment with piperacillin/tazobactam and 55 received cefepime or ertapenem. There was no difference in the proportion of patients who achieved clinical cure in the piperacillin/tazobactam group compared to the cefepime or ertapenem group (76.3% vs. 87.3%, P = 0.13). Treatment group was not associated with clinical cure when controlling for confounders in multivariable logistic regression (adjusted odds ratio [OR] 0.59, 95% confidence interval [CI] 0.15-2.37). The rate of recurrent pneumonia was 11.4% in the piperacillin/tazobactam group and 6.7% in the cefepime or ertapenem group (P = 0.48). Other secondary outcomes did not differ between the groups.. In this retrospective study of patients with Enterobacter pneumonia, clinical cure with piperacillin/tazobactam was comparable to that with cefepime or ertapenem; however, a prospective trial with a larger population is needed to determine if definitive treatment with piperacillin/tazobactam is non-inferior to definitive treatment with cefepime or ertapenem.

Topics: Aged; Anti-Bacterial Agents; Cefepime; Enterobacter; Enterobacteriaceae Infections; Ertapenem; Female; Humans; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Retrospective Studies; Treatment Outcome

 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 activities of ceftolozane-tazobactam and comparator agents against organisms deemed to be the cause of pneumonia among patients hospitalized in the United States during 2013 to 2015 were evaluated. Organisms included 1,576

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefepime; Ceftazidime; Cephalosporins; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Gene Expression; Hospitalization; Humans; Isoenzymes; Meropenem; Microbial Sensitivity Tests; Piperacillin, Tazobactam Drug Combination; Plasmids; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory System; Retrospective Studies; Tazobactam; United States

　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

Implementing a mouse model of Acinetobacter baumannii (AB) digestive colonization and studying the propensity of an intestinal reservoir of AB to be at the origin of pneumonia.. After a disruption of the digestive flora by piperacillin-tazobactam, two multidrug-resistant AB strains were intranasally inoculated to two cohorts of ten mice daily. For each strain, five mice were rendered transiently neutropenic.. One strain persisted several weeks in the digestive tract, even after stopping piperacillin-tazobactam injections, leading to the hypothesis that some AB strains can authentically colonize the gut. Most of the immunocompromised mice experienced clinical signs and positive lung cultures, which were associated with positive spleen cultures, an argument in favor of bacterial translocation.

Topics: Acinetobacter; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Translocation; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Gastrointestinal Tract; Immunosuppression Therapy; Lung; Mice; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial

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

 Tazobactam/piperacillin (TAZ/PIPC) is a combination antibiotic frequently used to treat pneumonia. It has recently been reported that TAZ/PIPC worsens renal function in patients with existing renal impairment. Creatinine clearance is generally between 10 and 40 mL/min in Japanese patients, so TAZ/PIPC is given at a dose of 2.25 g three times daily or 4.5 g twice daily. If pneumonia is severe or intractable, the dose frequency may be increased to 2.25 g four times daily and 4.5 g three times daily. We examined the effect of these different dosing regimens on renal function. We studied a cohort of 57 patients with impaired renal function hospitalized with pneumonia and treated with TAZ/PIPC between January 2015 and November 2016. Patients were classified into four groups according to TAZ/PIPC dose: 2.25 g three times daily (Group A); 2.25 g four times daily (B); 4.5 g twice daily (C) and 4.5 g three times daily (D). We examined the frequency of acute kidney injury (AKI) and treatment effectiveness. In Groups A, B, C and D, AKI occurred in 5.6%, 0.0%, 25.0% and 38.5% of patient. In groups C and D, hydration and dose reduction were required to address early signs of impending AKI. Our findings suggest that the higher TAZ/PIPC dose of 4.5 g was responsible for the decline in renal function, even if the dose frequency was reduced.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Retrospective Studies; Treatment Outcome

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

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

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

Inhalation injury is suspected in patients with facial and neck burn-injuries and in patients who suffered burns in an enclosed space. Inhalation injury is associated with a disappointingly high morbidity and mortality in spite of advances in diagnostics and therapy.Prophylactic antibiotic therapy in patients with diagnosed inhalation injury is still a controversial subject.The epidemiologic characteristics of the burn patients with diagnosed inhalation injury in our clinic receiving prophylactic antibiotic therapy and mortality of these patients will be referred in this study.. Patients >16 years of age admitted to the burn unit between January 2008 and December 2012 and fulfilling the burn center referral criteria according the German Burn Association were enrolled in the study.. 58 patients (male:female 47:11) were diagnosed with an inhalation injury by their admission. The average length of hospital stay was 27.5 days, whereas of the patients with no inhalation injury was 16 days (p=0.04). 56.9% of the patients underwent tracheostomy. An escalation of the antibiotic therapy was done in 39.7% of the patients with inhalation injury and in 20.3% of the patients without one. The mortality of inhalation injury patients was 12.1%.. The development of pneumonia is not influenced in a statistical significant way by the use of prophylactic antibiotics. We do recommend the administration of prophylactic antibiotic therapy to patients with diagnosed inhalation trauma, as the mortality of these patients was lower in comparison to other studies.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Burn Units; Burns; Burns, Inhalation; Case-Control Studies; Female; Humans; Length of Stay; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Respiration, Artificial; Retrospective Studies; Tracheostomy; Young Adult

The inoculum effect is a laboratory phenomenon in which the minimal inhibitory concentration (MIC) of an antibiotic is increased when a large number of organisms are exposed. Due to the emergence of extended-spectrum β-lactamase-producing Klebsiella pneumoniae (ESBL-Kpn) infections, the inoculum effect of ESBL-Kpn on β-lactams was studied in vitro and in vivo using an experimental model of pneumonia. The in vitro inoculum effect of 45 clinical ESBL-Kpn isolates on β-lactams was evaluated at standard (10(5) CFU/mL) and high (10(7) CFU/mL) organism concentrations. The MIC50 of piperacillin-tazobactam, cefotaxime and cefepime was increased eight-fold or more and that of meropenem was increased two-fold. The in vivo inoculum effect was evaluated in an ESBL-Kpn pneumonia mouse model treated with bacteriostatic effect-adjusted doses of piperacillin-tazobactam (1000 mg/kg four times daily, %T>MIC; 32.60%) or meropenem (100 mg/kg twice daily, %T>MIC; 28.65%) at low/standard (10(4) CFU/mouse) and high (10(6) CFU/mouse) inocula. In mice administered a low inoculum, no mice died after treatment with piperacillin-tazobactam or meropenem, whereas all the control mice died. In contrast, in the high inoculum model, all mice in the piperacillin-tazobactam-treated group died, whereas all meropenem-treated mice survived and had a decreased bacterial load in the lungs and no invasion into the blood. In conclusion, meropenem was more resistant to the inoculum effect of ESBL-Kpn than piperacillin-tazobactam both in vitro and in vivo. In the management of severe pneumonia caused by ESBL-Kpn, carbapenems may be the drugs of choice to achieve a successful outcome.

Topics: Animals; Anti-Bacterial Agents; Bacterial Load; Disease Models, Animal; Klebsiella Infections; Klebsiella pneumoniae; Lung; Male; Meropenem; Mice, Inbred BALB C; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Survival Analysis; Thienamycins

The aim of this study was to compare ceftolozane with ceftazidime, piperacillin/tazobactam (TZP) and imipenem in an experimental rabbit model of Pseudomonas aeruginosa pneumonia. Efficacy was assessed following 2 days of treatment by total colony counts in different tissues (lung, spleen and blood culture). Mean ± standard deviation pulmonary bacterial loads were 4.9 ± 0.3, 3.6 ± 0.3, 4.8 ± 0.2, 5.5 ± 0.8 and 3.9 ± 0.3 log₁₀CFU/g of lung for ceftolozane (1g), ceftolozane (2g), ceftazidime, TZP and imipenem, respectively, compared with 6.3 ± 0.9 log₁₀CFU/g of lung for control animals. The higher ceftolozane dose [2g three times daily (t.i.d.)] showed significantly better efficacy than the lower dose (1g t.i.d.). In conclusion, in this rabbit model of P. aeruginosa pneumonia, ceftolozane had an efficacy equivalent to that of comparator agents at a dose of 1g t.i.d. and had better efficacy at a higher dose (2g t.i.d.).

Topics: Animal Structures; Animals; Anti-Bacterial Agents; Bacterial Load; Ceftazidime; Cephalosporins; Colony Count, Microbial; Disease Models, Animal; Female; Humans; Imipenem; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Rabbits; Treatment Outcome

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

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

Topics: Anti-Bacterial Agents; beta-Lactamase Inhibitors; Coronary Vasospasm; Diagnosis, Differential; Electrocardiography; Follow-Up Studies; Humans; Infusions, Intravenous; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Syndrome

Topics: Adult; Animals; Anti-Bacterial Agents; C-Reactive Protein; Ceftriaxone; Ciprofloxacin; Female; Fusobacterium Infections; Humans; Hypoxia; Meningitis, Bacterial; Penicillanic Acid; Pets; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Rats; Respiratory Distress Syndrome; Streptobacillus; Thrombocytopenia

Meropenem is a carbapenem that has an excellent activity against many gram-positive and gram-negative aerobic, facultative, and anaerobic bacteria. The major objective of the present study was to assess the in vitro activity of meropenem compared to imipenem and piperacillin/tazobactam, against 1071 non-repetitive isolates collected from patients with bacteremia (55%), pneumonia (29%), peritonitis (12%) and wound infections (3%), in 15 French hospitals in 2006. The secondary aim of the study was to compare the results of routinely testings and those obtained by a referent laboratory.. Susceptibility testing and Minimum Inhibitory Concentrations (MICs) of meropenem, imipenem and piperacillin/tazobactam were determined locally by Etest method. Susceptibility to meropenem was confirmed at a central laboratory by disc diffusion method and MICs determined by agar dilution method for meropenem, imipenem and piperacillin/tazobactam.. Cumulative susceptibility rates against Escherichia coli were, meropenem and imipenem: 100% and piperacillin/tazobactam: 90%. Against other Enterobacteriaceae, the rates were meropenem: 99%, imipenem: 98% and piperacillin/tazobactam: 90%. All Staphylococci, Streptococci and anaerobes were susceptible to the three antibiotics. Against non fermeters, meropenem was active on 84-94% of the strains, imipenem on 84-98% of the strains and piperacillin/tazobactam on 90-100% of the strains.. Compared to imipenem, meropenem displays lower MICs against Enterobacteriaceae, Escherichia coli and Pseudomonas aeruginosa. Except for non fermenters, MICs90 of carbapenems were <4 mg/L. Piperacillin/tazobactam was less active against Enterobacteriaceae and Acinetobacter but not P. aeruginosa. Some discrepancies were noted between MICs determined by Etest accross centres and MICs determined by agar dilution method at the central laboratory. Discrepancies were more common for imipenem testing and more frequently related to a few centres. Overall MICs determined by Etest were in general higher (0.5 log to 1 log fold) than MICs by agar dilution.

Topics: Anti-Bacterial Agents; Bacteremia; France; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Peritonitis; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Thienamycins; Wound Infection

This study evaluated the pharmacodynamics of continuous infusion beta-lactams against pulmonary isolates of Gram-negative bacteria from patients managed in intensive care units (ICUs) in the USA. Multiple 10,000-patient Monte Carlo simulations were performed by integrating pharmacokinetic data from healthy individuals with 2408 MICs from the 2002 Intensive Care Unit Surveillance System database. These pharmacodynamic simulations suggested that continuous infusion regimens of cefepime, aztreonam, ceftazidime and piperacillin-tazobactam 13.5 g have the greatest likelihood of achieving pharmacodynamic targets against isolates of Enterobacteriaceae in the ICU. Beta-lactams are unlikely to achieve pharmacodynamic targets against Pseudomonas aeruginosa or Acinetobacter baumannii when administered as monotherapy.

Topics: Anti-Bacterial Agents; Aztreonam; beta-Lactams; Cefepime; Ceftazidime; Cephalosporins; Computer Simulation; Drug Combinations; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Intensive Care Units; Microbial Sensitivity Tests; Monte Carlo Method; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; United States

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

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 antibacterial activity of imipenem, cefepime and piperacillin-tazobactam alone or in combination with amikacin against a Pseudomonas aeruginosa strain producing an extended-spectrum beta-lactamase (PER-1) were compared using an experimental model of pneumonia in non-leucopenic rats. Animals were infected intratracheally with 8.0 +/- 0.4 log10 cfu of P. aeruginosa, and therapy was initiated 3 h later, by which time animal lungs showed bilateral pneumonia containing >7 log10 P. aeruginosa cfu/g of tissue. Since rats eliminate antibiotics much more rapidly than humans, renal impairment was induced in all animals to simulate the pharmacokinetic parameters of humans. MICs determined using an inoculum of 4 log10 cfu/mL were as follows: imipenem, 1 mg/L; cefepime, 8 mg/L; piperacillin-tazobactam, 32 mg/L; and amikacin, 16 mg/L. A noticeable inoculum effect was observed with the four antimicrobial agents tested, which was greatest for cefepime and piperacillin-tazobactam. In-vitro studies indicated that imipenem was the beta-lactam with the greatest bactericidal effect and that amikacin was synergic only in combination with cefepime and imipenem. Cefepime and piperacillin-tazobactam alone failed to decrease bacterial counts in the rats' lungs 60 h after therapy onset, whereas imipenem and, to a lesser extent, amikacin significantly reduced the number of viable microorganisms. Combination of amikacin with any of the three beta-lactams tested was synergic, despite a high amikacin MIC for the infecting strain. These results paralleled our in-vitro data showing a marked inoculum effect for cefepime and piperacillin-tazobactam. Based on the results of this study, the best treatment for infections caused by this type of extended-spectrum beta-lactamase-possessing strain would be imipenem plus amikacin.

Topics: Amikacin; Animals; Anti-Bacterial Agents; beta-Lactamases; Cefepime; Cephalosporins; Colony Count, Microbial; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Imipenem; Lung; Male; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Rats; Rats, Wistar

Bordetella bronchiseptica rarely causes disease in man, and is an unusual pathogen in animals. It causes a pertussis-like syndrome, but pneumonia and sepsis have been described in the immunocompromised as well as in the immunocompetent. A 53-year-old man with adult-onset diabetes and healed pulmonary tuberculosis presented with lobar pneumonia and rapidly developed septic shock with adult respiratory distress syndrome. He responded well to the combination of piperacillin-tazobactam.

Topics: Bordetella bronchiseptica; Bordetella Infections; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial