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PubMed1994

Piperacillin/tazobactam in the treatment of polymicrobial infections.

Polymicrobial infections are characterized by the presence of micro-organisms from more than one group of bacteria. Empirical treatment of polymicrobial infections requires an agent active against both anaerobic and aerobic/facultative bacteria. An aminoglycoside used in combination with an anti-anaerobe agent is commonly used to treat polymicrobial infections. However, aminoglycoside nephrotoxicity and treatment failures raise questions about the use of such regimens. Among non-aminoglycoside treatment regimens such as penicillin and cephalosporins, effectiveness has been compromised by bacteria producing extended spectrum beta-lactamases. Cefoxitin shows satisfactory results for treatment of intra-abdominal infections. Other studies have shown good results with imipenem, cefotetan and piperacillin used as single agents. Piperacillin/tazobactam, a new combination broad-spectrum antibiotic and potent beta-lactamase inhibitor, can be used for the treatment of infections caused by piperacillin-sensitive micro-organisms as well as beta-lactamase-producing, piperacillin-resistant organisms. This broad-spectrum activity is appropriate for infections traditionally treated empirically by double or triple antibiotic therapy.

Aminoglycosides↗
PubMed1990

Efficacy of prophylactic antimicrobial regimens in preventing infectious complications after transrectal biopsy of the prostate.

In a prospective study on 81 patients undergoing transrectal needle biopsy of the prostate, the efficacy of prophylaxis in preventing postbiopsy infectious complications was determined. The patients were divided randomly into four groups, and a comparison of the rate of postbiopsy complications in each group was made. In 11 and 17% of the patients in Group A (n = 18) who received povidone-iodine enema alone, bacteriuria and bacteraemia, respectively, occurred. When parenteral piperacillin alone in Group B (n = 22) was administered, the rates of the same complications were 9 and 14%, respectively, while both rates were as low as 4% in Group C (n = 25) when piperacillin in combination with povidone-iodine enema was given. On the other hand, in 31 and 37.5% of the patients in Group D (n = 16), who served as controls, bacteriuria and bacteraemia developed. The study has thus shown that parenteral piperacillin in combination with povidone-iodine enema significantly reduces the incidence of infectious complications associated with transrectal prostatic biopsy.

Aged↗
PubMed1999

Piperacillin/tazobactam plus tobramycin versus ceftazidime plus tobramycin as empiric therapy for fever in severely neutropenic patients.

The objective of this trial was to evaluate the potential advantages of the combination of piperacillin and tazobactam in the control of fever in neutropenic patients. In this single-center study, patients who experienced a total of 247 febrile episodes were prospectively randomized to receive either our standard regimen, ceftazidime 3 g/day (1 g t.i.d.) plus tobramycin 3 mg/kg per day (1.5 mg/kg b.i.d.), or piperacillin 12 g/day plus tazobactam 1.5 g/day (4 g+0.5 g t.i.d.) plus tobramycin 3 mg/kg per day (1.5 mg/kg b.i.d.). Vancomycin was added in all cases of persistent fever in the ceftazidime arm, but only when there was microbiologically documented resistance in the piperacillin/tazobactam arm. All 247 episodes were evaluable by "intent-to-treat" analysis. The two populations were well matched in terms of age, gender, underlying disease, chemotherapy received, oral decontamination, clinical and bacterial documentation, and severity and duration of neutropenia. Initial antibacterial therapy was successful (apyrexia at 72 h, without antibiotic change) more frequently (P = 0.008) with the regimen containing piperacillin/tazobactam (54.4%) than with the one including ceftazidime (37.6%). Fewer (P = 0.02) major infectious events (infectious death or delay in treatment of underlying disease due to infection) were observed during piperacillin/ tazobactam treatment (2.6%) than with the ceftazidime regimen (11.3%), despite a lower frequency of glycopeptide addition when piperacillin/tazobactam was used (54.4% versus 77.4%) according to the rules adopted. This trial confirmed the efficacy of the piperacillin/tazobactam combination for empirical treatment of febrile neutropenic patients. This antibiotic combination permitted a dramatic decrease in empiric glycopeptide antibiotic administration in such patients.

Adult↗
PubMed1985

Treatment of infections in hospitalized patients with ticarcillin plus clavulanic acid. A comparative study.

Ninety patients at the Wilmington Medical Center were enrolled in a comparative study to evaluate the efficacy and toxicity of ticarcillin plus clavulanic acid in the treatment of a variety of infections. Forty-seven women with obstetric or gynecologic infections were randomly assigned to receive ticarcillin plus clavulanic acid or cefoxitin. Forty-three patients with gram-negative septicemia or lower respiratory tract infection were given ticarcillin plus clavulanic acid or tobramycin plus piperacillin in a randomized fashion. Of the 47 women with obstetric or gynecologic infections, 23 were randomly assigned to receive ticarcillin plus clavulanic acid, and 24 were randomly assigned to receive cefoxitin. Several patients in each group had underlying diseases such as diabetes, obesity, and hypertension. Of the 27 pathogens isolated in the group receiving ticarcillin plus clavulanic acid, 26 (96 percent) were eradicated, including all three ticarcillin-resistant pathogens. In the cefoxitin-treated group, 31 of the 33 (94 percent) pathogens were eliminated, including all four ticarcillin-resistant organisms. Three reinfections or superinfections occurred, and cefoxitin therapy failed to eliminate an enterococcus isolate from the endometrium in one patient. The clinical response in both treatment groups was excellent. Either cure or clinical improvement was achieved for all 18 sites of infection in the ticarcillin plus clavulanic acid-treated group and for all 22 sites in the cefoxitin-treated group. There were no systemic drug reactions in either treatment group. In one patient in the cefoxitin-treated group, local phlebitis developed at the infusion site. This reaction responded to local therapy. There were no local reactions among the patients receiving ticarcillin plus clavulanic acid. Of the 43 patients with gram-negative septicemia or lower respiratory tract infection, 21 were randomly assigned to receive ticarcillin plus clavulanic acid and 22 were assigned to receive tobramycin plus piperacillin. Thirty-six patients had gram-negative sepsis, and seven patients had lower respiratory tract infection. Nine of the 36 patients suspected of having gram-negative sepsis were not evaluable because no pathogen was isolated prior to treatment. Twenty-two of the 27 patients treated for septicemia had good clinical and microbiologic responses. Three of the seven patients with pneumonia were not evaluable. Of the four evaluable patients, two had pneumococcus pneumonia; one was treated with tobramycin plus piperacillin and one with ticarcillin plus clavulanic acid. In both instances, the clinical and bacteriologic responses were considered good.

Adolescent↗
PubMed1991

Cytoprotection against neutrophil-delivered oxidant attack by antibiotics.

In the present study we have investigated the effect of six antibiotics (penicillin G, ceftazidime, cephotaxime, cephoperazon, ampicillin and piperacillin) on the neutrophil cytolytic activity by using a system constituted of phorbol-12-myristate-13-acetate-triggered neutrophils and 51Cr-labelled lymphoblastoid Daudi target cells. The results demonstrate that five of these drugs (ceftazidime, cephotaxime, cephoperazon, ampicillin and piperacillin) are capable of inhibiting the neutrophil cytolytic activity by inactivating the hypochlorous acid (HOCl) generated extracellularly by the myeloperoxidase pathway and crucial to the target cell lysis. Penicillin G had no effect on neutrophil-mediated cytolysis. Thus, these data demonstrate that ceftazidime, cephotaxime, cephoperazon, ampicillin and piperacillin lower the neutrophil-mediated target cell damage by a HOCl-scavenging mechanism, suggesting a possible cytoprotective role for these drugs during infections.

Ampicillin↗
PubMed1983

Beta-lactamase stability of cefoxitin in comparison with other beta-lactam compounds.

The beta-lactamase stability of cefoxitin, the second-generation cephamycin compound, was compared with that of cefamandole, cefoperazone, cefotaxime, moxalactam, carbenicillin, and piperacillin. Unlike cefamandole, cefoperazone, carbenicillin, and piperacillin, cefoxitin was not hydrolyzed by the common plasmid beta-lactamases, TEM-1, TEM-2, OXA-2, and SHV-1. Cefoxitin and moxalactam were the only agents stable to all chromosomal beta-lactamases, whereas cefamandole, cefoperazone, cefotaxime, carbenicillin, and piperacillin were destroyed by cephalosporinases of Proteus vulgaris and Bacteroides fragilis.

Anti-Bacterial Agents↗
PubMed1987

Determination of synergy by two methods with eight antimicrobial combinations against tobramycin-susceptible and tobramycin-resistant strains of Pseudomonas.

Eleven strains of tobramycin-susceptible Pseudomonas aeruginosa, 12 strains of tobramycin-resistant P. aeruginosa, and 11 strains of P. maltophilia were tested against tobramycin in combination with azlocillin, piperacillin, ceftazidime, and imipenem and against colistin in combination with azlocillin, piperacillin, ceftazidime, and imipenem by microdilution checkerboard and time-kill curve techniques. Synergistic or additive effects were demonstrated in the tobramycin-ceftazidime combination against tobramycin-resistant strains of P. aeruginosa and P. maltophilia, and with all tobramycin combinations against tobramycin-susceptible strains of P. aeruginosa using the checkerboard technique. Synergistic and additive effects were seen with the time-kill curve technique with colistin-ceftazidime, colistin-imipenem, and tobramycin-piperacillin combinations against tobramycin-susceptible P. aeruginosa and in the colistin-ceftazidime combination against tobramycin-resistant P. aeruginosa. Fractional inhibitory concentrations (FIC) and fractional bactericidal concentrations (FBC) from checkerboard studies were compared to the time-kill curve results and vice versa. The overall agreement with FIC was 39.4% and 40.9% and agreement with FBC was 40.9% and 43.9%. This limited study illustrates the lack of agreement between these techniques in demonstrating antimicrobial synergy against pseudomonads.

Azlocillin↗
PubMed1992

Non-nephrotoxic empiric antimicrobial therapy in febrile neutropenic cancer patients.

We evaluated the efficacy of piperacillin-pefloxacin as a non-nephrotoxic antibiotic combination in febrile neutropenic cancer patients treated with nephrotoxic chemotherapy. 40 patients: 34 with solid tumours and 6 with non-Hodgkin lymphoma, were treated during 55 episodes with: piperacillin 4 g intravenously every 8 h and pefloxacin 400 mg intravenously every 12 h. If the patient remained febrile after 72 h, 1 g vancomycin intravenously was added every 12 h. The mean duration of neutropenia was 7 days (range 3-13). Infection was microbiologically documented in 13 episodes (8 gram-positive cocci and 7 gram-negative bacilli). Temperature became normal in 38 patients with piperacillin-pefloxacin and 12 further episodes were resolved by the addition of vancomycin. 2 patients had an early change of antibiotics because of clinical deterioration, there were 2 protocol violations and 1 patient's temperature became normal after the addition of amphotericin. Neither septic death nor toxicity were observed. We conclude that this empirical treatment is active and safe and warrants further comparative trials.

Adolescent↗
PubMed2004

Evaluation of outpatient treatment with ertapenem in a double blind controlled clinical trial of complicated skin/skin structure infections.

OBJECTIVES: The patient characteristics and the efficacy and safety of ertapenem 1 g once daily vs. piperacillin-tazobactam 13.5 g divided Q6H were examined in patients who received outpatient parenteral antimicrobial therapy (OPAT) during a clinical trial of complicated skin/skin structure infections. METHODS: The population analyzed included 363 patients treated at US sites in a large randomized double-blind study. RESULTS: In this analysis, 146 (40%) patients at 19 (66%) sites were managed by OPAT. A lower proportion of treated patients who received OPAT had severe infection (12% vs. 20%, P=0.03). In evaluable patients managed by OPAT, 45 (83.3%) of 54 treated with ertapenem and 41 (82.0%) of 50 treated with piperacillin-tazobactam were cured at the test of cure assessment 10-21 days post-therapy (OR 1.2 (95% CI, 0.4-3.2), P=0.78). The safety profile of both drugs was generally similar; diarrhoea was the most common adverse event in both groups. CONCLUSIONS: In this trial of complicated skin/skin structure infection, OPAT was commonly used by US investigators. Among patients who received OPAT, ertapenem 1 g daily was as effective as piperacillin-tazobactam 3.375 g Q6H.

Adult↗
PubMed2005

Effects of pexiganan alone and combined with betalactams in experimental endotoxic shock.

To investigate the efficacy of pexiganan, a 22-residue magainin analog, alone and combined with betalactmas antibiotics in three experimental rat models of Gram-negative septic shock. Adult male Wistar rats were given (i) an intraperitoneal injection of 1 mg Escherichia coli 0111:B4 LPS; (ii) 2x10(10)CFU of E. coli ATCC 25922; and (iii) intra-abdominal sepsis induced via cecal ligation and puncture. For each model, all animals were randomized to receive intraperitoneally isotonic sodium chloride solution, 1 mg/kg pexiganan, 1 mg/kg polymyxin B, 20 mg/kg imipenem, 60 mg/kg piperacillin alone and combined with 1 mg/kg pexiganan. Each group included 15 animals. Lethality, bacterial growth in blood or intra-abdominal fluid, endotoxin and TNF-alpha concentrations in plasma. All compounds reduced the lethality when compared to controls. Piperacillin and imipenem significantly reduced the lethality and the number of E. coli in abdominal fluid compared with saline treatment. Pexiganan showed a slightly lower antimicrobial activity than betalactams even though it achieved a substantial higher decrease in endotoxin and TNF-alpha plasma concentrations than imipenem and piperacillin. No statistically significant differences were noted for antimicrobial and antiendotoxin activities between pexiganan and polymyxin B. Combination between pexiganan and betalactams showed to be the most effective treatment in reducing all variables measured. The use of a novel antimicrobial compound able to bind to LPS associated to potent antibiotics such as betalactams may become an important future consideration for sepsis treatment.

Animals↗
PubMed1985

Clinical pharmacology of extended-spectrum penicillins in infants and children.

Compared with previously available penicillins, piperacillin, azlocillin, and mezlocillin have increased activity in vitro against gram-negative bacilli. After intravenous administration of conventional doses (50 to 100 mg/kg) in children, peak concentrations of these drugs are approximately 70 to 350 micrograms/ml. For piperacillin, azlocillin, and mezlocillin, the half-lives during the beta elimination phase (t 1/2 beta) are approximately 0.5 to 0.75, 0.8 to 1.7, and 0.8 to 1.0 hours, respectively. In patients receiving the higher dosage, particularly of azlocillin, the t 1/2 beta may be prolonged by approximately 20%. A total daily dosage of 300 mg/kg or 9 gm/m2 given in four to six divided dosages should produce peak concentrations of approximately 150 micrograms/ml, and concentrations greater than 16 micrograms/ml for at least 2 hours after each administration. Lower daily dosages are needed in neonates, but precise dosage recommendations cannot be made at this time. Only approximately 60% of piperacillin and approximately 45% of azlocillin are eliminated unchanged in the urine; thus only modest dosage reductions are needed in patients with decreased renal function. In children, adverse effects have been infrequent.

Absorption↗
PubMed1995

Clinical use of beta-lactamase inhibitors in combination with extended-spectrum penicillins.

The in vitro antimicrobial spectrum of piperacillin-tazobactam is described and the results of clinical trials are summarized. Injectable products combining a beta-lactam antibiotic with a beta-lactamase inhibitor have a broad spectrum of activity, principally influenced by the potency of the beta-lactam. Piperacillin-tazobactam can be used for the treatment of infections caused by gram-negative, gram-positive, aerobic, and anaerobic bacteria. Appropriate indications include infections caused by mixed flora, such as gynecologic, intra-abdominal, and surgical wound infections. Other infections that appear responsive include those associated with human and animal bites, ischemic or diabetic foot infections, infected ischemic or pressure ulcers, and lower-respiratory-tract infections. Piperacillin-tazobactam has been reported to be superior to ticarcillin-clavulanate in community-acquired lower-respiratory-tract infections and superior to imipenem-cilastatin (at 1.5 g/day of imipenem) in intra-abdominal infection.

Abdomen↗
PubMed1995

Antibiotic prophylaxis for infectious complications after therapeutic endoscopic retrograde cholangiopancreatography: a randomized, double-blind, placebo-controlled study.

We performed a randomized, double-blind, placebo-controlled trial of antibiotic prophylaxis before diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in 82 uninfected patients with cholestasis due to biliary tree obstruction of single or multiple causes. The patients were assigned to receive piperacillin (4 g) or placebo three times daily; prophylaxis was started just before initial ERCP and was continued until biliary drainage was completely unobstructed (by one or more ERCP procedures); the maximal duration of prophylaxis was 7 days. Nine patients were withdrawn from the study, and five others could not be assessed because of protocol violations. The 68 clinically evaluable patients underwent 81 therapeutic ERCP procedures. Clinical success (defined as an absence of fever, cholangitis, and clinical signs of sepsis during the 48 hours after the last dose of piperacillin or placebo) was documented for 32 (94%) of the 34 patients given piperacillin and for 24 (71%) of the 34 patients given placebo (odds ratio, 6.66; P = .01). Complete biliary drainage influenced clinical outcome favorably (odds ratio, 5.0; P = .02). All seven instances of bacteriologic failure (bacteremia) involved patients in the placebo group (P < .01). We concluded that antimicrobial prophylaxis significantly reduces the incidence of septic complications after therapeutic ERCP among patients presenting with cholestasis.

Adult↗
PubMed1987

Platelet-mediated bleeding caused by broad-spectrum penicillins.

One hundred fifty-six hospitalized adult patients treated with ticarcillin, piperacillin, mezlocillin, or cefotaxime (control) were prospectively observed for determination of frequencies of platelet dysfunction and bleeding. Increases in bleeding times (greater than or equal to 5 min above pretreatment values) occurred in 73% of patients receiving ticarcillin, 43% receiving piperacillin, 25% receiving mezlocillin, and 17% receiving cefotaxime (P less than .0001); chemotherapy, thrombocytopenia, age of greater than or equal to 60 years, dose of greater than or equal to 12 g per day, and duration of treatment of six or more days were significant covariables. Significant bleeding occurred in 34% of patients treated with ticarcillin, 17% with piperacillin, 2% with mezlocillin, and 5% with cefotaxime (P = .0005); chemotherapy, thrombocytopenia, primary marrow disorders affecting platelet function, prolonged prothrombin time, and azotemia were significant covariables. Bleeding was associated with an elevated pretreatment bleeding time, an increase in bleeding time during treatment, and the maximal observed bleeding time during treatment (P less than .0001).

Adult↗
PubMed1985

In-vitro evaluation of cefpirome (HR 810), teicoplanin and four other antimicrobials against enterococci.

In-vitro activities of cefpirome (HR 810), a fourth generation cephalosporin, and teicoplanin were compared with those of ampicillin, piperacillin, and vancomycin against 56 clinical isolates of enterococci. Cefpirome had good activity with the MIC90 and MBC90 being 4 and 16 mg/l. Ampicillin and piperacillin had MBC90 of 4 and 16 mg/l. Teicoplanin was extremely active with the MIC90 being 1.6 mg/l while vancomycin had poor cidal activity with the MBC90 being 16 mg/l. A decrease in activity of cefpirome was noted when the inoculum size was increased from 10(3) to 10(7) organisms per ml. Synergy was demonstrated against most Streptococcus faecium isolates with a combination of cefpirome and gentamicin or piperacillin. Against Str. faecalis, with a similar combination, synergy was seen in less than 50% isolates. No antagonism was noted with any of the antibiotic combinations.

Ampicillin↗
PubMed1986

Comparative activities of the beta-lactamase inhibitors YTR 830, clavulanate and sulbactam combined with extended-spectrum penicillins against ticarcillin-resistant Enterobacteriaceae and pseudomonads.

The in-vitro synergistic activity of YTR 830, a new beta-lactamase inhibitor, combined with four extended-spectrum penicillins (ticarcillin, piperacillin, mezlocillin and apalcillin) against ticarcillin-resistant clinical isolates of Gram-negative enteric bacilli was compared with that of clavulanate and sulbactam. Synergy testing was performed with fixed concentrations of beta-lactamase inhibitors (8 mg/l) combined with doubling dilutions of beta-lactams in microdilution trays. Synergy was defined as a four-fold or greater decrease of beta-lactam MIC in the combination compared with the beta-lactam alone. For 79 ticarcillin-resistant Enterobacteriaceae, ticarcillin-YTR 830 and ticarcillin-clavulanate were synergistic against 90% of strains; for ticarcillin-sulbactam, 70% showed synergy. The synergistic activity of all three inhibitors was similar against strains resistant only to ticarcillin; for strains resistant to all four extended-spectrum penicillins, the activity of ticarcillin with YTR 830 and clavulanate was similar (synergy against 79% of strains) and superior to ticarcillin-sulbactam (synergy against 39% of strains). YTR 830 was more active than clavulanate against Serratia, Citrobacter, Proteus and Providencia spp. Piperacillin, mezlocillin and apalcillin susceptible strains, with MICs of 8-16 mg/l, showed synergy with inhibitors against 37-87% of strains. Amongst pseudomonads, no synergy was demonstrated against Pseudomonas aeruginosa; ticarcillin produced synergy with the inhibitors against Ps. maltophilia, while piperacillin-YTR 830 and apalcillin-YTR 830 were synergistic against Ps. cepacia. YTR 830 appears to have comparable in-vitro activity to that of clavulanate, and further development of this compound is warranted.

Ampicillin↗
PubMed1987

In-vitro antimicrobial activity of enoxacin in combination with eight other antibiotics against Pseudomonas aeruginosa, Enterobacteriaceae and Staphylococcus aureus.

Susceptibilities of 28 strains of Pseudomonas aeruginosa, 32 strains of Enterobacteriaceae and 24 strains of Staphylococcus aureus were tested against combinations of enoxacin with either cefsulodin, piperacillin, or amikacin, enoxacin with either aztreonam, latamoxef or amikacin, and enoxacin with either oxacillin, clindamycin or vancomycin, respectively. Synergy was detected by the agar dilution technique and was defined as a four-fold decrease in the inhibitory concentration of both drugs (sigma FIC less than or equal to 0.5). Against Ps. aeruginosa, synergy occurred in 28.5% of the strains for enoxacin plus cefsulodin, 17.6% for enoxacin plus piperacillin, and 3.7% for enoxacin plus amikacin. Against the Enterobacteriaceae, synergy was detected with enoxacin plus aztreonam, latamoxef or amikacin in 9.3%, 3.1% and 0% of strains, respectively. Against Staph. aureus, no synergy was demonstrable with enoxacin plus oxacillin, clindamycin or vancomycin. No antagonism was detected for any combination tested. Selected strains demonstrating synergy by the agar dilution method for enoxacin plus cefsulodin or piperacillin failed to show synergy in kinetic studies.

Amikacin↗
PubMed1992

Activity of antibiotics against resistant Pseudomonas aeruginosa.

The activity of 12 antibiotics, piperacillin, cefazolin, cefotiam, ceftizoxime, latamoxef, ceftazidime, cefuzonam, amikacin, ofloxacin, imipenem, aztreonam and minocycline, against 120 isolates of Pseudomonas aeruginosa was examined. In addition, the efficacy of antibiotics against single-, double-, or triple-drug-resistant isolates of P. aeruginosa were also examined to determine the cross-resistance to each drug. There was cross-resistance between piperacillin, ceftazidime and aztreonam, but amikacin and imipenem remained effective antibiotics, especially as salvage therapy, against isolates resistant to one agent. Results also suggested that piperacillin, ceftazidime or imipenem in combination with amikacin are effective combination regimens against most clinical isolates of P. aeruginosa. Amikacin and imipenem were also suitable antibiotics, especially as salvage therapy, against isolates of P. aeruginosa resistant to two agents. In conclusion, the results provide useful guidelines for choosing an effective treatment against clinical isolates of P. aeruginosa, and for choosing salvage therapy against resistant P. aeruginosa.

Amikacin↗