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PubMed2002

[Piperacillin-tazobactam in the treatment of severe nosocomial infections].

Epidemiology and clinical manifestations of nosocomial infections have been progressively evolving through last three decades. New pathogens, often associated to multiple antibiotic-resistances, are now among the leading etiologies in a patient population mainly represented by individuals debilitated by serious underlying diseases, immunosuppressive treatments and multiple diagnostic and therapeutic invasive procedures. Under these circumstances, when an infectious complication develops, prompt initiation of empiric antibiotic therapy, based on general and/or local epidemiology of nosocomial infections, may be crucial for survival of more critically ill patients. Based on recent data, the antibiotics of choice for treatment of nosocomial infections should have not only a bactericidal activity and a broad antibacterial spectrum, but also poor propensity to induce antibiotic-resistance and a satisfactory pharmacoeconomy profile. After a detailed description of the above mentioned context, the pre-eminent role of piperacillin-tazobactam in the treatment of nosocomial infections is reviewed and discussed.

Bacteria↗
PubMed1992

[A clinical study of transfer of cefminox and piperacillin into pulmonary tissue].

Serum concentrations of cefminox (CMNX) and piperacillin (PIPC) and their transfer into pulmonary tissue during surgery were serially studied following 1-hour intravenous instillation of 1 g of CMNX or PIPC immediately before thoracotomy, and the following results were obtained. Maximum serum concentrations of CMNX and PIPC were observed 1 hour after the commencement of administration, and their levels gradually decreased thereafter. The mean peak level of CMNX was 72.21 micrograms/ml, and T 1/2 was 1.62 hours. The mean peak level of PIPC was 43.26 micrograms/ml, and T 1/2 was 1.54 hours. In the pulmonary tissue, mean concentrations of CMNX in the normal pulmonary (alveolar) tissue were 28.80, 26.50 and 17.80 micrograms/g at 2.5, 3 and 4 hours, respectively, after the commencement of administration, and the corresponding levels for bronchiolar tissue were 19.6, 18.40 and 20.53 micrograms/g, respectively. The mean concentrations of PIPC in the normal pulmonary (alveolar) tissue were 18.97, 7.34 and 5.0 micrograms/g at 2, 3 and 4 hours, respectively, after the commencement of administration, and the corresponding levels for bronchiolar tissue were 7.2, 9.20 and less than 0.2 micrograms/g, respectively. PIPC also showed favorable transfer into the hilar lymph node tissue and obstructive pneumonitic lesions. The transfer of both drugs into pulmonary tissue suggests that both drugs are useful for the treatment of respiratory infectious diseases and the prevention of postoperative infections.

Adult↗
PubMed1992

[Comparative study of cefpiramide + amikacin versus piperacillin + amikacin in granulocytopenic patients: a randomized, prospective study].

Cefpiramide + amikacin (CPM + AMK) was compared in a prospective randomized trial with our standard regimen of piperacillin plus amikacin (PIPC + AMK) as an empiric therapy for fever in 252 episodes of 141 patients with granulocytopenia. Initial profound granulocytopenia (fewer than 100/mm3 mature granulocytes) was present in approximately 69% of the patient trials in both treatment groups. Both groups were equally distributed in regard to age, disease, pretreatment WBC count and duration of antibiotic treatment, although septic shock was more frequently seen in CPM + AMK. Responses to PIPC + AMK and CPM + AMK were similar for microbiologically and clinically documented infection, while the response rate for clinically documented infections treated with PIPC + AMK was superior to CPM + AMK (63% vs. 52%). Patients with persistent granulocytopenia of less than 100/mm3 of mature granulocytes without a rise during therapy responded significantly less in both groups (22% vs. 9%) than those in whom the granulocyte count rose (79% vs. 79%). Toxicities of jaundice or disordered hepatic function test were infrequent in both groups. Disordered renal function test occurred in one case in PIPC + AMK groups.

Adolescent↗
PubMed1992

[Protective effect by piperacillin against renal impairment caused by amikacin].

This study is aimed to demonstrate that renal impairment caused by administration of amikacin (AMK) alone can be lessened by co-administration of piperacillin (PIPC). The patients in the present study were divided into three groups. In "group P" and "group A", PIPC alone and AMK alone were administered, respectively. In "group P+A", PIPC and AMK were co-administered. Dosage of AMK was individualized based upon the therapeutic drug monitoring method, and that of PIPC was adjusted depending upon the creatinine clearance of a patient. In group A, urinary concentrations of beta 2-microglobulin and lysozyme, and urinary excretion of beta 2-microglobulin, lysozyme and gamma-GTP per day were significantly higher (p less than 0.05) than those in group P. These differences were not observed, however, between group P and group P+A. The trough value of AMK, 11 days after AMK administration, was significantly higher in group A (p less than 0.05) than that in group P+A. Incidence of renal impairment, as judged from urinary excretion of beta 2-microglobulin per day and urinary lysozyme concentration, was significantly higher in group A (p less than 0.05) than that in group P+A. These findings indicate that co-administration of PIPC with AMK can lessen the renal impairment caused by administration of AMK alone.

Adult↗
PubMed1991

[In vitro activity of tazobactam and piperacillin combination against 224 strains of Pseudomonas aeruginosa according to the production of beta-lactamase].

Piperacillin (PIP) alone and combined with 4 mg/l, 8 mg/l of tazobactam (TAZ) were tested by MIC determination on Mueller-Hinton agar against 224 clinical strains of P. aeruginosa: "wild type" (BLA-), 32 producing a constitutive cephalosporinase (CEP), 41 producing the PSE-1 type beta-lactamase, 7 PSE-2, 8 PSE-3, 9 PSE-4, 13 TEM-1, 24 TEM-2, 13 OXA-1, 22 OXA-2, 5 OXA-3. The combination with 8 mg/l was more effective than that one with 4 mg/l. Combinations of PIP-TAZ 8 mg/l reduced the MICs of PIP for the resistant strains (MICs greater than 64 mg/l) to the susceptible ot the moderately susceptible range (MICs less than or equal to 64 mg/l) for 31% of the CEP producing strains, 63% of the PSE-1, 15% of the PSE-2, none of the PSE-3, 34% of the PSE-4, 39% of the TEM-1, 30% of the TEM-2, 23% of the OXA-1, 14% of the OXA-2, 27% of the OXA-3, TAZ is the first beta-lactamase inhibitor effective against the constitutive cephalosporinase of P. aeruginosa; it is also very effective against the most frequently found PSE-1 beta-lactamase in P. aeruginosa.

Cephalosporinase↗
PubMed1991

[In vitro antibacterial activity of piperacillin-tazobactam combination on hospital isolates and regression curve].

Minimal inhibitory concentrations (MICs) of piperacillin (P) in combination with 4 micrograms/ml of tazobactam (T) were evaluated by agar dilution for 1,245 strains isolated in 4 hospitals. In addition antibiograms by agar diffusion were performed with disks loaded of 75 micrograms of P + 10 micrograms of T. For naturally non beta-lactamase producing Enterobacteriaceae (E), MIC 50 and 90% of P + T were (microgram/ml): E. coli 1-2; P. mirabilis: 0.5-1; activity was practically identical on plasmid mediated penicillinase (Pase) producing strains. Strains of K. pneumoniae only resistant (R) to amino- and carboxypenicillins (C) had MICs less than or equal to 4 (mode MIC 2); MICs of strains R to cephalothin and/or cefotaxime were 2 to 16 (mode MIC 4). For chromosomal cephalosporinase (Case) producing species, MICs of P + T were less than or equal to 8, including for acquired Pase producing strains, but were greater than or equal to 16 for Case hyperproducing strains. Strains of P. aeruginosa susceptible (S) to C were inhibited by 1 to 16 (with MIC 4) and strains R to C by 8 to greater than 128. MICs were generally 2 to 32 for A. baumannii S to C at 0.12 to greater than 128 for strains R to C. Haemophilus, S or R to ampicillin, were inhibited by 0.008 to 2 (MIC 50 and 90: 0.016-0.12). S. aureus S to methicillin (M), Pase producing on not, were inhibited by 0.5 to 2 (mode MIC 1) and strains R to M by 8 to greater than 128. Activity of P + T for coagulase-Staphylococci was similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Acinetobacter↗
PubMed1991

[Antimicrobial activity of piperacillin in vitro].

There was an increase in the resistance of clinical isolates to piperacillin as compared to that in 1987-1988. It was shown on the kinetic models that there was difference in the effect of the inhibitory and subinhibitory concentrations of the drug on microorganisms in various growth phases. No post-antibiotic action against Staphylococcus aureus and Pseudomonas aeruginosa and a slightly pronounced dose-dependent effect with respect to Escherichia coli were noted.

Culture Media↗
PubMed1991

[Treatment of severe infections in hematologic malignancies with piperacillin sodium].

Combination antibiotic therapies using piperacillin (PIPC) were evaluated in 60 episodes of severe infections in 38 neutropenic patients with hematologic malignancies. 1. The overall efficacy rate was 46.7%. Efficacy rates were 30% in patients with pneumonia, 60% in patients with sepsis and 50% in patients with suspected sepsis in which causative organisms were not identified. 2. Eradication rates were 44.4% for Gram-negative bacilli, 50% for Pseudomonas aeruginosa and 22.2% for Gram-positive cocci. 3. Efficacy rates were 33.3% in patients with initial count of neutrophil less than 100/microliters, 60% in patients with those 100 to 500/microliters and 66.7% in patients with those higher than 500/microliters. Initial neutrophil counts correlated well with efficacies of PIPC on severe infection in patients with hematologic malignancies. 4. Mild increases of transaminase were observed in 2 cases. From these results it is concluded that PIPC is one of the most important antibiotics in the treatment of severe infections in neutropenic patients with hematologic malignancies.

Adolescent↗
PubMedDate not supplied

Treatment of pelvic inflammatory disease with combined piperacillin and minocycline therapy.

Pelvic inflammatory disease (PID) has its aetiopathogenesis especially in anaerobic microorganisms and it is considered that 15% of patients with PID do not respond to initial treatment, 20% have at least one recurrence and 18% become sterile. Forty-six patients aged between 18 and 45 treated as out-patients with the association piperacillin-minocycline have been considered. These patients were monitored up to 5 weeks from the start of therapy following standard evaluation criteria and it is held that this therapy is effective and indicated as a first approach.

Adolescent↗
PubMed1990

[Evaluation of the effectiveness of sodium piperacillin in the treatment of surgical infections in children].

A clinical trial has been carried out in 40 children (age ranging from 2 to 12 years) with postsurgical infections caused by aerobic, anaerobic and facultative bacteria. All have been treated by monotherapy with sodium piperacillin, with doses of 150-200 mg/kg daily in 3 administrations. The drug was administered for a mean period of 7 days, by intravenous infusion or intramuscular route. The causative organism was eradicated in all but 4 cases (90%). Side effects observed were all of mild intensity, and in no case it was necessary to discontinue the treatment with the drug. Both bacterial and clinical results indicate a high tolerability and a very rapid effectiveness of this antibiotic.

Bacterial Infections↗
PubMed1990

[Combined effect of sulbactam/cefoperazone and other antibiotics against clinical isolates of multi-resistant strains. I. Effect of sulbactam against beta-lactams resistant strains and in vitro combined effect of sulbactam/cefoperazone with each of piperacillin, latamoxef, ceftazidime, fosfomycin and doxycycline].

We evaluated relationships between production of beta-lactamase and their resistances to beta-lactams, effect of sulbactam (SBT), a beta-lactamase inhibitor, against beta-lactam resistant strains, and combined effect of sulbactam/cefoperazone (SBT/CPZ) with other antibiotics against multi-resistant strains. Through these studies, we obtained the following results. 1. Most of the strains resistant to beta-lactams were beta-lactamase producers. 2. Relationships between the production of beta-lactamase and their resistances to beta-lactams indicate that their resistances generally were the highest in producers of both penicillinase (PCase) and cephalosporinase (CEPase), moderate in producers of either PCase or CEPase, and the lowest in beta-lactamase non-producers. Most of highly-resistant strains of MRSA appeared to be beta-lactamase non-producers though some exceptions were observed among methicillin-resistant Staphylococcus aureus (MRSA), Serratia marcescens and Pseudomonas aeruginosa. 3. SBT showed good effect against PCase producers, moderate effect against producers of both PCase and CEPase, little effect against CEPase producers, and no effect against beta-lactamase non-producers. 4. Results of combined effect of SBT/CPZ with other antibiotics indicated that good synergism was obtained by combining SBT/CPZ with fosfomycin (FOM) or piperacillin against multi-resistant strains of Proteus spp., Enterobacter cloacae, and S. marcescens, by combining SBT/CPZ with ceftazidime (CAZ) or FOM in methicillin-sensitive S. aureus and by combining SBT/CPZ with CAZ in P. aeruginosa. 5. Better synergism was obtained with the higher concentrations of antibiotics.

Anti-Bacterial Agents↗
PubMed1990

[Clinical laboratory approach in estimating effective administrative dose of piperacillin. Reevaluation of MIC break points in 3 and 4 category systems of disc susceptibility test].

The reliability of the piperacillin (PIPC) disc susceptibility test in estimating approximate values of MICs was studied with various clinical isolates totaling 284 strains using Showa discs and the discs prepared in this laboratory (both 8 mm diameter containing 30 micrograms of PIPC). Clinical significance of a 4 category system for the interpretation of the PIPC disc tests, which is widely used in Japan, was reevaluated to determine whether this system would be suitable or not for the evaluation of proper dose levels of administration. Break points in MIC values proposed for the classification of bacteria into 4 categories of susceptibility were: ( ) MIC less than or equal to 3 micrograms/ml, (++) MIC greater than 3-15 micrograms/ml, (+) MIC greater than 15-60 micrograms/ml, (-) MIC greater than 60 micrograms/ml. A 3 category system for interpreting of disc test, which is generally used in the USA and Europe, was also evaluated. MIC break points in the 3 category system proposed for the classification of the PIPC test are sensitive (S) MIC less than or equal to 64 micrograms/ml and resistant (R) MIC greater than or equal to 256 micrograms/ml. In addition, British Society for Antimicrobial Chemotherapy recently proposed in vitro MIC break points for PIPC in therapeutic use, recommending MICs 16 and 64 micrograms/ml. MIC 16 micrograms/ml can be used for general infections treated with usual administrative doses for such infections and MIC 64 micrograms/ml may apply to increased dosage or to normal dosage when PIPC is locally concentrated (mainly urinary or biliary tract infections). The results obtained with the disc method were compared with MICs determined using the agar dilution method at an inoculum level of 10(6) CFU/ml. The results of the PIPC disc susceptibility test either with Showa discs or discs prepared in this laboratory were well correlated with MICs, showing the reliability of the disc method in estimating approximate values of MICs. In the 4 category classification system of the Showa disc test, 33 out of 284 strains (11.6%) tested showed false positive results and 5 strains (1.8%) false negative results. Similarly, in the test of 30 micrograms discs prepared in this laboratory, of 284 strains 26 (9.2%) showed false positive results and 8 (2.8%) false negative results. In the tests of Showa discs and discs prepared in this laboratory, both containing 30 micrograms of PIPC, no inhibitory zones were observed against the strains with MIC greater than 100 micrograms/ml.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacteria↗
PubMed1989

[Piperacillin in the therapy of severe bacterial infections: comparison of its efficacy and tolerance vs. ceftazidime].

38 patients with severe acute bacterial systemic infections have been enrolled in this study: 19 patients were treated with piperacillin (100-200 mg/kg/day) and 19 with ceftazidime (45-90 mg/kg/day) by i.v. route. In both groups monotherapy has been found effective and well tolerated. Serious side-effects have not been observed. The high cure and eradication rates in both groups do not show statistically significant differences (chi 2 = 0.620 and chi 2 = 0.219, respectively, p greater than 0.05).

Adult↗
PubMed1989

[Efficiency of tazobactam as inhibitor of beta-lactamases, combined with piperacillin, against resistant strains to this penicillin].

We studied the efficacy of tazobactam (YTR 830), a new beta-lactamase inhibitor in combination with piperacillin (P) against 198 Enterobacteriaceae strains. A comparative study of susceptibility (MIC determined on Mueller Hinton agar; inoculum 10(4) cfu) was made with the combination amoxicillin (A) + clavulanic acid (CA). Of 181 strains resistant to P, 79.56% were susceptible to it in the presence of tazobactam (TZ). The characteristics of the beta-lactamases of 37 strains resistant to P + TZ (MIC greater than 40 micrograms/ml) were studied; 11 were hyperproducers of chromosomic beta-lactamase and 7 produced two types of plasmidic beta-lactamase. The MICs of TZ alone were uniform and high (64-128 micrograms/ml), independently of the characteristics of the strains beta-lactamase. Of 17 strains susceptible to P, the efficacy of P + TZ was significant among carriers of plasmidic beta-lactamase; there was practically no change in the P susceptibility among the non carriers. The efficacy of P + TZ was similar to that of A + AC against E. coli strains; it was higher against strains of Enterobacter, Citrobacter and Serratia.

Amoxicillin↗
PubMed1989

A new model of bacterial peritonitis in mice for evaluation of antibiotics. Effects of aspoxicillin and piperacillin.

Experimental peritonitis was produced in mice with Escherichia coli TPRL 10760 derived from the intestinal flora of mouse and used to evaluate the chemotherapeutic effects of semisynthetic penicillins, aspoxicillin (ASPC) and piperacillin (PIPC). The peritonitis was induced by inserting a gelatin capsule containing the bacterial cells, sterilized cecal contents and BaSO4 into the pelvic cavity of an anesthetized mouse. Infection with more than 10(6) colony forming units (CFU) of the bacteria/mouse resulted in an acute peritonitis associated with 100% mortality, whereas an inoculum size of 10(2) CFU/mouse produced a chronic peritonitis. In the mice with acute peritonitis, administration of 100 mg/kg x 5 times of ASPC reduced the mortality to 0% but administration of 100 mg/kg x 5 times of PIPC did not reduce the mortality. In the mice with chronic peritonitis, ASPC was more effective than PIPC in decreasing the number of viable bacterial cells in the peritoneal fluid. The superiority of ASPC over PIPC was attributable to its higher bactericidal activity as well as its high drug level and more persistency in the peritoneal fluid as compared to PIPC.

Amoxicillin↗
PubMed1989

Cefotetan versus piperacillin in the prophylaxis of abdominal and vaginal hysterectomy: a prospective randomized study.

A prospective randomized study was carried out on a total of 686 patients who underwent vaginal or abdominal hysterectomy. Of these, 338 were given prophylactic cefotetan (2 g) and 348 piperacillin (2 g). Both drugs were administered as i.v. bolus 30 min before operation. Findings confirm the higher risk of infection with abdominal hysterectomy and the advantages of the long half-life cephalosporin, cefotetan.

Cefotetan↗
PubMed1989

[In vitro bactericidal effect of a piperacillin-pefloxacin combination against isolated strains of nosocomial pneumopathies in intensive care].

Combinations of piperacillin and pefloxacin are evaluated in vitro using checkerboard and killing-curves methods against 19 clinical isolates: S. aureus, K. pneumoniae, K. oxytoca, C. freundii, P. stuartii, Ps. aeruginosa, Ps. maltophilia and Ac. anitratum. The static checkerboard method showed more synergistic antibacterial effects than the killing curves method. The best synergistic effects appeared against S. aureus, K. oxytoca, P. stuartii, Ps. aeruginosa Ac. anitratum, including a notable increase of the rapidity of bactericidal activity. The combination PIP 64 micrograms - PEF 4 micrograms prevents the frequent secondary regrowth seen after 6 hours with the antibiotics used alone. No activity is obtained against S. aureus meti-R and Ps. maltophilia.

Cross Infection↗
PubMed1986

[In vitro effect of piperacillin on aerobic bacteria. Variations according to the phenotypes of resistance to beta-lactam antibiotics].

In a first study the MICs of piperacillin (PIP), mezlocillin (MEZ), azlocillin (AZL), carbenicillin (CARB) and ticarcillin (TIC) against 563 strains of aerobic bacteria were compared. The MIC50 of PIP against E. coli and P. mirabilis was 0.5 to 1 mg/l, that is equal to those of MEZ and TIC but 2 or 3 times lower than those of AZL and CAR. The MIC50 of PIP and MEZ against Klebsiella, a species that is naturally resistant to TIC and CAR, was 4 mg/l. Enterobacter, Serratia and Citrobacter showed two populations of strains: the first was sensitive to the five penicillins tested (MIC50 of PIP: 1 to 2 mg/l); the second was resistant to all of them. PIP and AZL were more active (MIC50 8 mg/l) against Ps. aeruginosa than MEZ, TIC and CAR. All five penicillins had limited activity against Acinetobacter (MIC50 less than 16 mg/l). PIP, MEZ and AZL were more active than TIC and CAR against enterococci. In a second study, the activity of PIP was evaluated by standard sensitivity tests on 4993 strains of enterobacteria, Ps. aeruginosa and Acinetobacter classified according to their phenotype of resistance to beta-lactam antibiotics. PIP was regularly active against enterobacteria and Ps. aeruginosa strains devoid of acquired resistance. The activity of PIP was significantly reduced against enterobacteria strains with a phenotype suggesting induced penicillinase production. However, the inhibition zone diameters, although reduced, remained within what is now considered the sensitivity range (notably with E. coli and Proteus spp), which raises the problem of in vitro tests interpretation. PIP was active against E. coli strains with a "cephalosporinase" phenotype, but inactive against cefotaxime resistant strains of: Enterobacter, Citrobacter and Serratia. The activity of PIP on CAR-resistant Ps. aeruginosa strains was significantly reduced, but the inhibition zone diameter in one quarter of them was still within limits of sensitivity.

Azlocillin↗