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[In vitro synergistic activity of piperacillin-tazobactam combination against beta-lactam antibiotics resistant strains of Enterobacteriaceae].

The combination of piperacillin and tazobactam was studied in a microtiter checkerboard assay against 160 strains of Enterobacteriaceae selected for their resistance pattern to amoxicillin, ticarcillin, cephalothin and cefotaxime. Mean FIC indices were respectively 0.02, 0.17 and 0.01 for RRSS strains of E. coli, K. pneumoniae and P. mirabilis. Mean FIC indices were 0.03 for RRRI/R strains of K. pneumoniae producing a broad spectrum beta-lactamase, but the synergistic effect was out of therapeutic range for 16 strains of 20. Mean FIC indices were 0.53, 0.90, 0.55, 0.10 and 0.21 respectively against RSRS strains of E. coli, E. cloacae, S. marcescens, M. morganii and P. vulgaris. Mean FIC indices were 0.02, 0.07, 0.02 and 0.01 against RRRS/R strains of E. coli, E. cloacae, S. marcescens and M. morganii but they were in a therapeutical range (piperacillin less than or equal to 8 mg/l and tazobactam less than or equal to 4 mg/l) respectively for 7, 0, 4 and 10 strains of 10 in each species. Tazobactam restored the antibacterial activity of piperacillin against enterobacterial strains mainly producing a penicillinase or a cephalosporinase for M. morganii and P. vulgaris.

Anti-Bacterial Agents↗

[Evaluation of synergistic enhancement of antimicrobial activities of piperacillin and amikacin against Pseudomonas aeruginosa using FIC index and disc diffusion method].

A preliminary study was carried out to see whether or not the synergistic enhancement of antimicrobial activity of piperacillin (PIPC) and amikacin (AMK) in combinations against Pseudomonas aeruginosa can be evaluated using combination discs of these antibiotics. A synergistic antimicrobial effect was observed between these antibiotics, when evaluated using FIC index, against piperacillin-sensitive strains with MIC less than or equal to 12.5 micrograms/ml under the conditions of the present investigation using the agar dilution method. However, no synergy was found between these antibiotics against piperacillin-resistant strains with MIC greater than or equal to 25 micrograms/ml, even when a higher concentrations of the drugs were used. Using strains of P. aeruginosa against which the synergistic effect between these antibiotics was observed, it was found that inhibitory diameters obtained with combination discs of PIPC/AMK at concentrations of 30 micrograms/30 micrograms or 30 micrograms/15 micrograms were more than 3 mm larger than those obtained with discs containing either PIPC or AMK alone. Using strains against which no synergistic effects were observed, however, the above mentioned enlargement of inhibitory zone diameters with combination discs were not clearly found. Further studies are deemed necessary to determine whether or not the combination discs of PIPC and AMK are useful in routine clinical work.

Amikacin↗

Biliary pharmacokinetic profile of piperacillin: experimental data and evaluation in man.

The purpose of the present experimental and clinical work is to revisit the biliary pharmacokinetic properties of piperacillin. Whereas the up to now published data result from microbiological assays, this work was realized by high performance liquid chromatography. In the isolated and perfused rabbit liver model (n = 5; 3 h), the biliary level peaked at 1,013 +/- 305 micrograms/ml between 30 and 60 min. During the experiments, 56.7% and 10.8% of the administered piperacillin (10 mg) were respectively eliminated in bile and submitted to hepatic biotransformation. In man, a single 2 g i.v. dose was administered to 6 volunteers. The excretion measured in the duodenal fluid was 1,681 +/- 601 micrograms in 4 h (0.08% of the administered dose). In cholecystectomized patients (n = 10) provided with a T-drain, the biliary peak concentration was 211 +/- 64 micrograms/ml during the 2nd h, and the 24 h biliary elimination was 12,963 +/- 3,332 micrograms, representing 0.65% of the administered dose. The hepato-biliary clearance was 0.80 ml/min. On per-operatively collected serum, choledocal bile, gallbladder bile and gallbladder wall samples (n = 10 patients), the concentrations of piperacillin simultaneously measured 1 h after the i.v. administration of 2 g were respectively, 81.7 +/- 20.5, 382 +/- 110, 30.8 +/- 2.5 micrograms/ml and 10.5 +/- 2.6 micrograms/g.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Short-term antibiotic prophylaxis in surgery. Our experience with the use of piperacillin in 261 patients].

Personal experience of short-term chemoprophylaxis with piperacillin in 261 consecutive "clean" and "non-contaminating" operations is reported. Piperacillin was employed in a dose of 2 g i.m. every 8 hours for a total of 48 hours, the first administration being carried out at the same time as pre-anaesthesia. Results of the study showed 8 cases (3.06%) of hyperpyrexia (greater than 38.5 C for at least 3 days) and no cases of wound, bronchopulmonary or urinary infection or systemic sepsis were encountered. It is concluded that the use of piperacillin enables "clean" and "non-contaminating" general surgery interventions to be carried out almost without risk of infection.

Bacterial Infections↗

[Piperacillin and amikacin in the treatment of infections in neoplasm patients with granulocytopenia].

Infections are the most common cause of death in tumor patients. The risk of infection is progressively increased in relation to the severity of neutropenia. It is therefore essential to start empirical antibiotic therapy in these patients at the first sign of infection. Forty-three neutropenic tumor patients were entered into the above study when it was assumed that they had bacterial infections (temperature above 38.5 degrees C and/or signs and symptoms of infection). Patients with greater than 1000 neutrophils/mm3 were given piperacillin alone while those with more severe neutropenia (less than 1000/mm3) were given a combination of piperacillin plus amikacin. Of the 43 patients who had entered the study, 41 could be evaluated whereas the remaining two were considered dropouts either because of non-compliance with the study protocol or because the infection was found to be non-bacterial. In both groups of patients (greater than 1000 and less than 1000 neutrophils/mm3) infection resolved completely in a large percentage of cases (92% and 82%, respectively). The efficacy of piperacillin was therefore reconfirmed for the management of infection in oncologic patients with neutropenia, and proved to be an effective therapeutic resource in patients with both slight and severe neutropenia.

Adolescent↗

[Indications for piperacillin in pediatrics].

The clinical activity of piperacillin was evaluated in 34 children (mean age: 8 years) presenting with severe infection (septicaemia, meningitis, bronchopneumonia, pyelonephritis). A bacteriological diagnosis was established in 24 cases. The mean duration of treatment was 11 days, and the mean dose 220 mg/kg/day administered in three injections. In 25 cases piperacillin was combined with another antibiotic, usually an aminoglycoside (20 cases). Clinical cure or improvement was obtained in 29 children (85%). Treatment was well tolerated, with only 2 cases of moderate blood eosinophilia. In view of these results the authors suggest that piperacillin could be used in children in two circumstances: severe infections caused by Gram-negative cocci or bacilli in children with cystic fibrosis or neutropenia, and against infections contracted in intensive care units, or in children with febrile leucopenia, combined with an aminoglycoside in the absence of, or pending bacteriological results.

Adolescent↗

[Effects of piperacillin on the immunologic functions of macrophages].

In this study, the possible effects of piperacillin on three immune functions of human blood monocytes-macrophages were investigated. Monocytes and macrophages were isolated from the circulating blood of normal subjects by density gradient centrifugation followed by adhesion to plastic material. The cells were incubated for 30 to 60 min with different concentrations of piperacillin, then tested on the following models: presentation by the monocytes-macrophages of an exogenous antigen to autologous lymphoid cells, with evaluation of the proliferative response to tuberculin; secretion of interleukin-1 by monocytes-macrophages stimulated or not by lipopolysaccharide, with measurement of the culture supernatants ability to stimulate rat thymocytes; release to prostaglandin E2 by monocytes-macrophages with evaluation of its indomethacin-inhibitable suppressive effect on lymphoproliferative responses to a polyclonal mitogen. In none of these tests did piperacillin show and immunodepressant or immunostimulant effect.

Antigen-Presenting Cells↗

Stability of clindamycin phosphate with aztreonam, ceftazidime sodium, ceftriaxone sodium, or piperacillin sodium in two intravenous solutions.

In admixtures containing clindamycin and either aztreonam, ceftazidime, ceftriaxone, or piperacillin in either 5% dextrose injection (D5W) or 0.9% sodium chloride injection (NS), the stability of each drug was studied. Each of the following combinations of drugs was added to 100-mL glass bottles of base solution: clindamycin phosphate 0.9 g and aztreonam 2.0 g, clindamycin phosphate 0.9 g and ceftazidime sodium 2.0 g, clindamycin phosphate 1.2 g and ceftriaxone sodium 2.0 g, and clindamycin phosphate 0.9 g and piperacillin sodium 4.0 g. Duplicate samples were prepared. Admixtures containing each single drug were also tested. Samples were visually inspected and tested for pH and drug concentration immediately after mixing and at 1, 4, 8, 12, 24, and 48 hours of storage in room temperature and light. Drug concentrations were determined by high-performance liquid chromatographic assay methods. Ceftriaxone retained greater than 90% of its original concentration for 24 hours in single-drug admixtures in NS, for eight hours with clindamycin in NS, and for one hour with clindamycin in D5W. Ceftazidime retained greater than 90% potency for 24 hours with clindamycin in D5W. In all other test admixtures, all drugs were stable for 48 hours. Under the conditions studied, clindamycin is compatible in the admixtures tested with aztreonam and piperacillin. Admixtures of clindamycin and ceftazidime in D5W should be used within 24 hours at room temperature. Clindamycin and ceftriaxone can be mixed in NS if administered within eight hours, but ceftriaxone is stable for only one hour in combination with clindamycin in D5W.

Aztreonam↗

A comparison of piperacillin, cephalothin and cefoxitin in the prevention of postoperative infections in patients undergoing vaginal hysterectomy.

A randomized, double-blind, multicenter trial was initiated to compare the safety and efficacy of piperacillin, cephalothin and cefoxitin in the prophylactic treatment of patients undergoing vaginal hysterectomy. The total dose of each antibiotic was 6 grams given in three equally divided doses. A satisfactory prophylactic response was obtained in 143 of 151 (95 per cent) patients treated with piperacillin, in 82 of 87 (94 per cent) patients treated with cephalothin and in 57 of 60 (95 per cent) patients treated with cefoxitin. The pooled data indicated that the piperacillin treatment group did not differ from the combined cephalosporin treatment groups with respect to prophylactic response, presence of febrile morbidity, fever index, duration of postoperative hospitalization and incidence of reported adverse experiences.

Adult↗

[Effectiveness of piperacillin in childhood infections].

Piperacillin is a semisynthetic penicillin with a broad-spectrum: in particular it is active against Gram positive, Gram negative, aerobic and anaerobic bacteria often resistant to other antibiotics of the same group. We report a trial carried out on 38 children with severe and moderate infections treated with piperacillin. We have considered ESR, all leucocytes count and body temperature. No severe side effects have been reported. Piperacillin must be used as a first choice in pediatric age, mostly in case of mixed bacterial infections and in immunocompromised patients.

Adolescent↗

[Comparative sensitivity of 207 strains of strict anaerobic bacteria to piperacillin and 4 other antibiotics].

The MIC of two hundred and seven anaerobic bacterial strains was determined by an agar dilution method for five antibiotics (piperacillin, ampicillin, carbenicillin, cefalotin, metronidazole). 100% of the strains were susceptible to carbenicillin (MIC less than or equal to 128 mg/l), 97% to piperacillin (MIC less than or equal to 16), 86% to metronidazole (MIC less than or equal to 4), 70% to ampicillin (MIC less than or equal to 4) and 68% to cefalotin (MIC less than or equal to 8). Amongst bêta-lactam compounds, piperacillin and ampicillin determined the lowest MIC for Bacteroides fragilis, Fusobacterium, Clostridium and Gram-positive cocci. Amongst Bacteroides fragilis strains, the lowest MIC were obtained with metronidazole.

Ampicillin↗

In vitro activity of piperacillin and other microbials on 491 bacterial isolates.

We tested the activity of piperacillin against 491 bacterial local clinical isolates in comparison with ampicillin, mezlocillin, cefazolin, cefoperazone, cefotaxime, ceftazidime, moxalactam, and gentamicin, using an agar dilution technique and inocula of 10(6) and 10(4) colony forming units. The results confirmed the broad-spectrum activity of piperacillin against a wide range of bacterial pathogens. The activity against Pseudomonas aeruginosa was encouraging, and it was one of the most active agents tested against that species. Its lack of stability for certain types of beta-lactamases was manifested by large differences in the minimal inhibitory concentration (MIC) activity between inocula of 10(6) and 10(4), and by the high MIC to inhibit 90% of strain of certain species compared with the MIC to inhibit 50% of strain. The activity of piperacillin suggests its clinical evaluation for use in combination with other agents in serious sepsis, in situations where beta-lactamase-producing strains are rare, and in antipseudomonal therapy.

Anti-Bacterial Agents↗

[Piperacillin: microbiological and clinical studies].

A microbiological and clinical study of the action of piperacillin is presented. The drug showed an excellent in vitro antibacterial action on gram positive and gram negative microorganisms. Its in vitro action on Ps. aeruginosa (70.8% of strains inhibited) was also extremely interesting, making it the second most effective of the antibiotics tested after polymyxin B and colistin, polypeptides unsuitable for clinical use. In vivo, the administration of piperacillin achieved a clinical and bacteriological cure in 35 out of 40 patients and a clinical cure in 2 out of 40. It was only therapeutically unsuccessful in 3 cases. It is concluded that its microbiological, kinetic and tolerance features make piperacillin suitable for a wide range of therapeutic purposes.

Acinetobacter↗

[Apalcillin: in vitro activity compared with that of carbenicillin, ticarcillin, mezlocillin, piperacillin against Enterobacteriaceae and Acinetobacter].

The in vitro activity of apalcillin was compared with that of carbenicillin, ticarcillin, mezlocillin and piperacillin against clinical isolates of Enterobacteriaceae and Acinetobacter. 1 168 strains were tested by a routine disk diffusion method. They were grouped into different patterns of resistance by results to ampicillin, carbenicillin and cephalotin. The MICs were determined for 300 of these strains. Apalcillin, mezlocillin and piperacillin are active against most strains of E. coli, P. mirabilis, Klebsiella and C. diversus resistant to carbenicillin and ticarcillin. Apalcillin is the most active penicillin against Acinetobacter; it is almost as active as piperacillin, the best drug against Enterobacteriaceae.

Acinetobacter↗

[Penetration of piperacillin into the cerebrospinal fluid of patients with purulent meningitis].

Ten patients with purulent meningitis received 3 intravenous injections of 4 g piperacillin at intervals of 8 hours, in addition to the usual antimicrobial treatment. Piperacillin was assayed in serum and CSF by high performance liquid chromatography. The mean CSF concentration of the drug was 9.2 micrograms/ml and its mean percentage of penetration was 22,7%. There were no significant differences in CSF concentrations between days 2 to 4 (inflamed meninges) and days 10 to 20 (patient cured). It is concluded that piperacillin shows good CSF penetration and could be useful to treat selected cases of meningitis due to Gram-negative bacilli.

Adolescent↗

In vitro susceptibilities of mucoid Pseudomonas aeruginosa isolates from cystic fibrosis patients against azthreonam, netilmicin and piperacillin.

Minimum bacteriostatic (MIC) and bactericidal (MBC) levels were done on 37 clinical isolates of mucoid Pseudomonas aeruginosa from cystic fibrosis patients against azthreonam, netilmicin and piperacillin. Results show that piperacillin had the greatest bacteriostatic activity; however there was more likely to be a significant disparity between MIC and MBC with this drug. Netilmicin was less active than piperacillin, but there was less difference between MICs and MBCs. Azthreonam was the least active compound tested.

Anti-Bacterial Agents↗

Clinical evaluation of piperacillin therapy for infection.

Piperacillin sodium, a semisynthetic penicillin that inhibits many Klebsiella and Pseudomonas aeruginosa organisms resistant to carbenicillin, was used to treat 41 episodes of infection in 35 patients. Infectious sites included lungs, urinary tract, and tissue, including peritonitis. Seven patients had bacteremia. Clinical and bacteriological cures were achieved in 85% of infections. Cure was achieved with piperacillin in patients infected with carbenicillin-resistant P aeruginosa and Klebsiella organisms. Adverse effects were minor and included rash in two patients. Serum levels were easily maintained above the inhibitory levels for susceptible organisms. Piperacillin was a safe, well-tolerated, and effective antimicrobial agent.

Adolescent↗

In vitro activity of azlocillin, carbenicillin, mezlocillin and piperacillin against Pseudomonas aeruginosa.

50% inhibitory concentration (IC50) of azlocillin, carbenicillin, mezlocillin and piperacillin against 157 strains of P. aeruginosa were determined by means of the agar plate-dilution method. The 3 new semisynthetic penicillins were significantly more active against P. aeruginosa than carbenicillin; azlocillin and piperacillin were 8-fold, and mezlocillin was 2-4-fold more active than carbenicillin. More than 95% of the P. aeruginosa strains were inhibited by 16 micrograms/ml of azlocillin or piperacillin whereas 64 micrograms/ml of mezlocillin and 256 micrograms/ml of carbenicillin, respectively, were necessary to inhibit 95% of the strains.

Azlocillin↗