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PubMed1993

The efficacy and safety of piperacillin/tazobactam in the therapy of bacteraemia.

The efficacy of the combination of piperacillin plus tazobactam was studied in 142 patients who had a bacteriologically proven bacteraemia. Seventy-three patients were bacteriologically evaluable and, of these, 55 had a follow-up blood culture; there was no follow-up culture in the other 18 patients, so that any cure could only be presumptive. Of the 55 patients who were fully followed up, 32 received only piperacillin and tazobactam and 23 also received an aminoglycoside. Overall, there were 67 cures and six failures out of 73 evaluable cases (three Staphylococcus aureus, two Staphylococcus epidermidis and one Streptococcus bovis). There were 11 deaths, eight of which occurred in neutropenic patients. In no case was death drug related. Side-effects were mild; the commonest adverse events noted were mild elevations of liver enzymes. Piperacillin plus tazobactam appeared efficacious and safe in the therapy of bacteraemia.

Abdomen↗
PubMed1993

The activity of piperacillin/tazobactam against clinical isolates collected in 20 UK centres and the design of a disc test for susceptibility testing.

The in-vitro activities of piperacillin plus tazobactam at ratios of 4:1, 8:1 and 16:1 were determined against 952 non-copy clinical aerobic bacterial isolates collected from 20 UK centres. Tazobactam enhanced the activity of piperacillin against Enterobacteriaceae, Staphylococcus aureus, Haemophilus influenzae and Moraxella catarrhalis. No enhancement was noted for Pseudomonas aeruginosa, other Pseudomonas spp., streptococci and enterococci. For 95.6% of strains MICs were either the same or only one two-fold dilution different with all the three ratios of tazobactam, and for most of the remaining strains the piperacillin MIC was lowest with the highest proportion of the tazobactam (4:1). The percentage of strains which remained resistant was also lowest with the 4:1 ratio. Regression analysis of MICs versus inhibition zone size with a variety of disc strengths tested on DST agar indicated that for Enterobacteriaceae, and H. influenzae 30 +4 micrograms, and 5 +1 microgram piperacillin/tazobactam discs gave the most reliable results. However, for S. aureus no disc gave good discrimination. Zone sizes obtained on DST and Iso-Sensitest agar were similar, with 96.1% of 1450 paired tests showing agreement to within 3 mm.

Bacteria, Aerobic↗
PubMed1993

Multicentre survey of the comparative in-vitro activity of piperacillin/tazobactam against bacteria from hospitalized patients in the British Isles.

Twenty-nine British and Irish hospitals each collected up to 300 bacterial isolates from in-patients. The organisms were identified by an appropriate API system or, for staphylococci, by their Gram and coagulase reactions. Disc susceptibility tests were performed. Isolates that gave zones < or = 25 mm to piperacillin/tazobactam (75 micrograms + 10 micrograms) discs were sent to a central laboratory for re-examination and determination of MIC, together with a sample of the more susceptible organisms. Results were evaluated for 6724 isolates. Over 95% of the isolates of Escherichia coli, klebsiellae, Proteus mirabilis, Pseudomonas aeruginosa, Haemophilus, Moraxella and Bacteriodes, spp. streptococci, pneumococci and Enterococcus faecalis were susceptible to piperacillin/tazobactam (defined as giving a zone > or = 22 mm to a 75 micrograms + 10 micrograms disc), as were 86% of Acinetobacter spp. and 82% of the Citrobacter, Enterobacter, Morganella and Serratia group. Tazobactam particularly extended the activity of piperacillin against E. coli isolates (96% susceptible cf. 61% to piperacillin alone) klebsiellae (95% cf. 70%), P. mirabilis (99% cf. 86%), and Acinetobacter spp. (86% cf. 53%). Occasional (18%) resistance in Enterobacter, Serratia and Citrobacger spp. was probably caused by stable depression of Class I beta-lactamases, which are inhibited poorly by tazobactam. High resistance frequencies (> 25%) were found for Enterococcus faecium and Xanthomonas maltophilia. Tazobactam potentiated piperacillin against beta-lactamase-producing methicillin-susceptible Staphylococcus aureus, but the mode inhibition zone of piperacillin/tazobactam discs was only 26 mm, compared to 38 mm for beta-lactamase-negative isolates. Nevertheless, fewer than 5% of the enzyme producers appeared resistant to 8 + 4 mg/L piperacillin/tazobactam in MIC tests. Similar behaviour was noted for coagulase-negative staphylococci. Amongst the eleven comparator drugs, ceftazidime, gentamicin and ciprofloxacin were as active as piperacillin/tazobactam against most enterobacteria. However, Acinetobacter and Bacteroides spp. and enterococci were resistant to ceftazidime, and Bacteroides spp., enterococci, pneumococci and other streptococci were inherently resistant to ciprofloxacin and gentamicin. Cefuroxime, ampicillin and co-amoxiclav had narrower spectra. Only imipenem showed a consistently wider spectrum and lower frequency of resistance than piperacillin/tazobactam.

Bacteria, Anaerobic↗
PubMed1996

The efficacy of antibiotics enhanced by electrical currents against Pseudomonas aeruginosa biofilms.

Low electrical currents are reported to enhance the activity of tobramycin and biocides against biofilm bacteria. We report that the activity of those antibiotics to which the bacterium is susceptible in its planktonic state may be enhanced by a low electrical current against the more resistant biofilm cells. Pseudomonas aeruginosa biofilms were formed on a dialysis membrane suspended between two parallel electrode plates in an electrical colonisation cell. Ciprofloxacin, polymyxin B and piperacillin were tested on biofilms at ten times their MIC for 12 h in the presence of 0 (control) and 9 mA/cm2 current density. At these concentrations the antibiotics alone reduced the biofilm population, but in the presence of an electrical current the population was further reduced by ciprofloxacin and polymyxin B though not by piperacillin. Exposure of the planktonic bacteria to the same concentrations of antibiotics demonstrated that ciprofloxacin and polymyxin B reduced the population to below 1% after 12 h and below 0.1% after 24 h, while piperacillin was bacteriostatic. The results suggest that the electrical current can enhance the activity against biofilms of only those antibiotics that are effective against planktonic cells.

Anti-Bacterial Agents↗
PubMed2000

Effect of conalbumin on the activity of Syn 2190, a 1,5 dihydroxy-4-pyridon monobactam inhibitor of AmpC beta-lactamases.

Syn 2190, a 1,5 dihydroxy-4-pyridon monobactam inhibitor of AmpC enzymes, was tested against beta-lactamase-producing bacteria with piperacillin, piperacillin-tazobactam and ceftazidime as partner drugs. In the presence of conalbumin as an iron chelator, Syn 2190 potentiated these drugs against most AmpC producers, although Klebsiella spp. with plasmidic AmpC enzymes were an exception. Potentiation was much weaker without conalbumin, suggesting that Syn 2190 exploits a ferric uptake pathway, as do catecholic cephalosporins. Syn 2190 had little ability to potentiate partner drugs against strains with other beta-lactamase types but, with conalbumin, increased the activity of piperacillin-tazobactam against Escherichia coli transconjugants producing various class A or D enzymes.

Bacterial Proteins↗
PubMedDate not supplied

In-vitro and in-vivo activity of parenterally administered beta-lactam antibiotics against Chlamydia trachomatis.

The extended-spectrum penicillins ticarcillin, mezlocillin, and piperacillin might be useful as single agents for the treatment of pelvic infections in women if it could be shown that these drugs are active against Chlamydia trachomatis. We found that the MIC90 (concentration at which 90% of strains are inhibited) values of ticarcillin, mezlocillin, and piperacillin were 16, 16, and 64 micrograms/ml, respectively. Several cephalosporins were found to have MICs for C. trachomatis of greater than 200 micrograms/ml. Ten women with postpartum endometritis who were colonized with C. trachomatis had repeated chlamydial cultures following treatment with beta-lactam antibiotics. All seven cases treated with ticarcillin plus clavulanic acid (a beta-lactamase inhibitor) or piperacillin alone had C. trachomatis-negative cultures after treatment. Three of four of these women had negative cultures at a second follow-up visit. In contrast, the three women treated with a cephalosporin were culture-positive at their first follow-up clinic visit. These data suggest that there is a correlation between the in-vitro measurement of beta-lactam antibiotic activity against C. trachomatis and the microbiologic outcome of treatment. We conclude that the extended-spectrum penicillins deserve further evaluation as single agents for the treatment of pelvic infections in women at high risk for C. trachomatis infections.

Adult↗
PubMed2005

Recurrent Alcaligenes xylosoxidans keratitis.

PURPOSE: To describe a case of postkeratoplasty recurrent Alcaligenes xylosoxidans keratitis. METHODS: A 33-year-old man with a history of penetrating keratoplasty developed corneal infiltrate with intact epithelium and then was treated with broad-spectrum antibiotics. Corneal scraping was taken for microbiologic study. RESULTS: The culture result identified A. xylosoxidans, sensitive to piperacillin and ceftazidime. There were 3 recurrent episodes within 2 months after each apparent resolution achieved after the instillation of topical piperacillin (10 mg/mL). During the fourth attack, the lesion responded poorly to piperacillin and ceftazidime (25 mg/mL), so therapeutic penetrating keratoplasty was performed to eradicate the recalcitrant infection. CONCLUSIONS: A. xylosoxidans has probably been underreported as a cause of ocular infection. It does not respond to conventional antibiotic therapy and may be difficult to eradicate. Therapeutic penetrating keratoplasty might be necessary if medical treatment fails.

Abscess↗
PubMed2004

Cecropin B enhances betalactams activities in experimental rat models of gram-negative septic shock.

OBJECTIVE: To investigate the efficacy of imipenem, piperacillin combined with cecropin B in the prevention of lethality in 2 rat models of septic shock. Main outcome measures were bacterial growth in blood and intra-abdominal fluid, endotoxin and TNF-alpha concentrations in plasma, and lethality. BACKGROUND: Sepsis remains a serious clinical problem despite intense efforts to improve survival. It is a major cause of morbidity and mortality in hospitalized patients. The primary cause of Gram-negative shock results from activation of host effector cells by endotoxin, the lipopolysaccharide (LPS) associated with cell membranes of Gram-negative bacteria. METHODS: Adult male Wistar rats were given (1). an intraperitoneal injection of 1 mg of Escherichia coli 0111:B4 LPS or (2). 2 x 1010 CFU of E. coli ATCC 25922. All animals were randomized to receive intraperitoneally isotonic sodium chloride solution, 1 mg/kg cecropin B, 20 mg/kg imipenem, and 120 mg/kg piperacillin alone and combined with 1 mg/kg cecropin B. Each group included 20 animals. RESULTS All compounds reduced the lethality when compared with controls. Piperacillin and imipenem significantly reduced the lethality and the number of E. coli in abdominal fluid compared with saline treatment. On the other hand, each betalactam determined an increase of plasma endotoxin and TNF-alpha concentration. Combination between cecropin B and betalactams showed to be the most effective treatment in reducing all variables measured. CONCLUSION: Cecropin B enhances betalactams activities in Gram-negative sepic shock rat models.

Animals↗
PubMed1998

[A case of hypoxemic acute bronchiolitis presenting with diffuse nodular shadows caused by Mycoplasma pneumoniae].

A fifty year-old female who had previously been well presented with a productive cough and a high fever. Her initial chest X-ray film showed no abnormal lung shadows. Despite partial improvement of the fever and the serum level of acute phase reactant (CRP) in response to intravenous administration of piperacillin, she complained of increasing severity of cough and dyspnea. Follow-up chest X-ray films taken five days after therapy with piperacillin showed diffuse nodular shadows in the mid-to-lower lung fields bilaterally. Chest CT scan disclosed diffuse miliary nodules at the lung periphery and thickening of bronchovascular markings. Chest auscultation revealed late inspiratory coarse crackles and expiratory wheezing, and the patient's arterial oxygen tension was 61 mmHg. Suspected of suffering from primary atypical pneumonia, she was started on therapy with intravenous minocyclin (200 mg/day), two days after treatment her symptoms began improving significantly. Anti-mycoplasma antibody was found to be x 1280, and cold hemoagglutinin x 1024, establishing the diagnosis of Mycoplasma pneumoniae infection. The patient's condition completely recovered following a one week treatment with minocyclin. We concluded that her respiratory infection was caused by piperacillin-sensitive mico-organism, and also Mycoplasma pneumoniae which brought about hypoxic acute bronchiolitis to the patient.

Acute Disease↗
PubMed1986

BRL-36650: in vitro studies and assessment of serum bactericidal activity after single-dose administration in volunteers.

Ten healthy volunteers received 1 g of BRL-36650, a new formamido-penicillin derivative, given by intravenous infusion over 15 min. Levels in serum were measured microbiologically 30, 60, and 120 min after the start of the 15-min infusion and were (mean +/- standard deviation) 102.7 +/- 28.4, 59.7 +/- 11.5, and 9.6 +/- 1.9 mg/liter, respectively. A total of 10 strains each of Escherichia coli, Klebsiella pneumoniae, Serratia spp., and Enterobacter spp. and 14 strains of Pseudomonas aeruginosa were selected according to their susceptibility or resistance to piperacillin for the study of serum bactericidal activity (SBA). The MICs and MBCs of these strains were influenced by the choice of medium. Median SBA against E. coli and K. pneumoniae were greater than or equal to 1:2,048 and 1:512, respectively. The SBA against piperacillin-susceptible Serratia spp. (1:256), Enterobacter spp. (1:128), and P. aeruginosa (1:32) were significantly higher than against piperacillin-resistant strains (1:32, 1:8, and 1:4, respectively). Killing curves confirmed the high bactericidal activities obtained against the majority of strains. In the case of one Enterobacter sp. and one P. aeruginosa isolate with an MBC greater than or equal to 32, the absence of killing was noted.

Female↗
PubMed1987

Effect of broad-spectrum parenteral antibiotics on composition of intestinal microflora of humans.

We compared the effects of four beta-lactam drugs with widely differing antibacterial and pharmacological properties on the composition of the intestinal flora. Cefoxitin, piperacillin, cefoperazone, and aztreonam were given intravenously for 9 days to healthy volunteers. Cefoperazone reduced the numbers of aerobic and anaerobic bacteria to undetectable levels. At the other extreme, cefoxitin had little effect on the normal flora. Aztreonam markedly reduced the numbers of aerobes, whereas piperacillin had a variable effect on both aerobic and anaerobic bacteria. There was extensive overgrowth of enterococci in subjects given cefoxitin or aztreonam, which have little activity against this species, and of yeasts in subjects given cefoperazone or piperacillin. Cefoperazone reached concentrations of 2,727 to 8,840 micrograms/g in the feces, whereas the other agents were generally undetectable. These results show that the new beta-lactam antibiotics produce widely varying effects on the fecal microflora after parenteral administration and that these effects are consistent with the antibacterial and pharmacological properties of the drugs.

Adult↗
PubMed1988

Enhanced phagocytosis, killing, and serum sensitivity of Escherichia coli and Staphylococcus aureus treated with sub-MICs of imipenem.

The influence of pretreatment of Escherichia coli and Staphylococcus aureus with sub-MICs of the new beta-lactam antibiotic imipenem on phagocytosis and killing by murine peritoneal macrophages and the susceptibility of these organisms to serum bactericidal activity were studied. The effects of imipenem, a round form inducer in gram-negative rods, and piperacillin, a filamentous form inducer, were compared. Bacteria grown in the presence of sub-MICs of imipenem or piperacillin were incubated for 30 min with macrophage monolayers in the absence of antibiotic. Phagocytosis, killing, and survival within macrophages were evaluated by microbiological and fluorescence microscope assays. Bacteria grown in the presence of a sub-MIC of imipenem were phagocytized and killed in numbers significantly higher than untreated or piperacillin-treated bacteria were. Intracellular bacteria pretreated with a sub-MIC of imipenem were also readily killed by lymphokine-activated macrophages. Prior treatment with a sub-MIC of imipenem resulted in an increased susceptibility of E. coli but not S. aureus to the bactericidal activity of immune serum. Imipenem treatment and immune serum acted synergistically to enhance phagocytosis and killing. The data indicate that exposure of E. coli and S. aureus to a sub-MIC of imipenem enhances the susceptibility of these potential pathogens to cellular and humoral host defense mechanisms.

Antibody Formation↗
PubMed1997

Antimicrobial susceptibility of flavobacteria as determined by agar dilution and disk diffusion methods.

A total of 106 clinical isolates of flavobacteria, including 41 isolates of Flavobacterium meningosepticum, 59 of Flavobacterium indologenes, and 6 of Flavobacterium odoratum were collected from January 1992 to December 1995 from patients in Taiwan. The in vitro activities of antimicrobial agents were determined concomitantly by the standard agar dilution and disk diffusion methods. More than 90% of the flavobacterial isolates were resistant to cephalothin, cefotaxime, ceftriaxone, moxalactam, aztreonam, imipenem, aminoglycosides, erythromycin, and glycopeptides. The majority of F. meningosepticum isolates were susceptible to piperacillin and to minocycline but resistant to ceftazidime, with MICs at which 90% of the isolates are inhibited being 8, 4, and > 128 microg/ml, respectively. Approximately half of the F. indologenes isolates were susceptible to piperacillin, cefoperazone, ceftazidime, and minocycline, with MICs at which 50% of the isolates are inhibited being 4, 16, 8, and 4 microg/ml, respectively. The majority of F. odoratum isolates were resistant to all the antimicrobial agents tested except minocycline, to which five of six isolates were susceptible. With least-squares regression analysis and error rate-bounded analysis methods, the following resistant and susceptible zone diameter breakpoints were established: < or = 12 and > or = 17 mm, respectively, for piperacillin against F. meningosepticum and F. indologenes; < or = 13 and > or = 18 mm, respectively, for ceftazidime against F. meningosepticum and F. indologenes, < or = 17 and > or = 21 mm, respectively, for ofloxacin against F. indologenes; < or = 16 and > or = 20 mm, respectively, for ciprofloxacin against F. meningosepticum. Valid breakpoints for the disk diffusion method could not be established for cefoperazone and ofloxacin against F. meningosepticum and for minocycline against F. meningosepticum and F. indologenes due to a poor correlation coefficient for the regression line or for cefoperazone and ciprofloxacin against F. indologenes due to the presence of remarkable error rates.

Anti-Bacterial Agents↗
PubMed1999

Clavulanate induces expression of the Pseudomonas aeruginosa AmpC cephalosporinase at physiologically relevant concentrations and antagonizes the antibacterial activity of ticarcillin.

Although previous studies have indicated that clavulanate may induce AmpC expression in isolates of Pseudomonas aeruginosa, the impact of this inducer activity on the antibacterial activity of ticarcillin at clinically relevant concentrations has not been investigated. Therefore, a study was designed to determine if the inducer activity of clavulanate was associated with in vitro antagonism of ticarcillin at pharmacokinetically relevant concentrations. By the disk approximation methodology, clavulanate induction of AmpC expression was observed with 8 of 10 clinical isolates of P. aeruginosa. Quantitative studies demonstrated a significant induction of AmpC when clavulanate-inducible strains were exposed to the peak concentrations of clavulanate achieved in human serum with the 3.2- and 3.1-g doses of ticarcillin-clavulanate. In studies with three clavulanate-inducible strains in an in vitro pharmacodynamic model, antagonism of the bactericidal effect of ticarcillin was observed in some tests with regimens simulating a 3.1-g dose of ticarcillin-clavulanate and in all tests with regimens simulating a 3.2-g dose of ticarcillin-clavulanate. No antagonism was observed in studies with two clavulanate-noninducible strains. In contrast to clavulanate. No antagonism was observed in studies with two clavulanate-noninducible strains. In contrast to clavulanate, tazobactam failed to induce AmpC expression in any strains, and the pharmacodynamics of piperacillin-tazobactam were somewhat enhanced over those of piperacillin alone against all strains studied. Overall, the data collected from the pharmacodynamic model suggested that induction per se was not always associated with reduced killing but that a certain minimal level of induction by clavulanate was required before antagonism of the antibacterial activity of its companion drug occurred. Nevertheless, since clinically relevant concentrations of clavulanate can antagonize the bactericidal activity of ticarcillin, the combination of ticarcillin-clavulanate should be avoided when selecting an antipseudomonal beta-lactam for the treatment of P. aeruginosa infections, particularly in immunocompromised patients. For piperacillin-tazobactam, induction is not an issue in the context of treating this pathogen.

Anti-Bacterial Agents↗
PubMedDate not supplied

Comparative serum bactericidal activity against Pseudomonas aeruginosa of six antipseudomonal agents.

Serum levels and serum bactericidal activities of six antipseudomonal agents were studied comparatively in 60 patients. Single intravenous doses of gentamicin (1.5 mg/kg), piperacillin (4 g), ceftazidime (1 g), imipenem (0.5 g), aztreonam (1 g), and ciprofloxacin (200 mg) were given over 30 min to 10 patients each, and serum samples were obtained 30 min, 1, 2, 3, 4, 6, 8 and 12 h after beginning the infusion. Serum bactericidal activity was determined by the broth microdilution method against 10 recent isolates of Pseudomonas aeruginosa. Mean peak serum levels were as follows: gentamicin 10.4 micrograms/ml, piperacillin 227.5 micrograms/ml, ceftazidime 43.5 micrograms/ml, imipenem 17.3 micrograms/ml, aztreonam 42.3 micrograms/ml, and ciprofloxacin 3.9 micrograms/ml. All agents demonstrated effective serum bactericidal activity (geometric mean titer > 1:2) at peak serum levels. Ceftazidime was by far the most potent compound with a mean titer of 1:46.5, followed by ciprofloxacin (1:17), imipenem (1:13.7), and aztreonam (1:13.4). Ceftazidime also showed the longest duration of activity with a mean titer of 1:5.1 at 4 h. Based on our results, ceftazidime appeared to be the most potent antipseudomonal agent, while gentamicin and piperacillin were the least effective.

Anti-Bacterial Agents↗
PubMedDate not supplied

Susceptibility of clinical isolates to expanded-spectrum beta-lactams alone and in the presence of beta-lactamase inhibitors.

Tazobactam and BRL 42715 are relatively new penems which inhibit a wide range of plasmid- as well as chromosomally mediated bacterial beta-lactamases that include Richmond and Sykes type I, II, III, IV and V beta-lactamases, staphylococcal penicillins and extended-spectrum beta-lactamases. However, clavulanic acid, which is a potent inhibitor of class III beta-lactamases, is one of the first discovered compounds. We used a total of 645 recent clinical isolates, consisting of 305 Enterobacteriaceae, 180 gram-positive cocci and 160 other gram-negative bacteria to evaluate the ability of beta-lactamase inhibitors for potentiation of piperacillin, ticarcillin and amoxycillin. Minimum inhibitory concentrations for all the 42 strains of methicillin-susceptible Staphylococcus aureus were reduced 4- to 16-fold in the presence of beta-lactamase inhibitors. They were also highly effective in inhibiting the beta-lactamase of a wide variety of gram-negative bacteria, thereby changing their MIC values for amoxycillin, ticarcillin and piperacillin from a 'resistant' to a 'susceptible' range. Commonly resistant bacteria like Klebsiella, Enterobacter, Serratia, Acinetobacter and Pseudomonas were rendered susceptible to piperacillin and ticarcillin in the presence of clavulanic acid, tazobactam and BRL 42715. Of the commercially available formulations for clinical use, piperacillin/tazobactam (Tazocin) was found to be more inhibitory towards both gram-positive and gram-negative bacteria.

Amoxicillin↗
PubMed1997

Assessment of the enzymuria resulting from gentamicin alone and combinations of gentamicin with various beta-lactam antibiotics.

OBJECTIVE: To determine the propensity of beta-lactam antimicrobials to ameliorate or potentiate aminoglycoside-induced renal enzymuria. DESIGN: Two open, randomized, double-blind, parallel-group studies were conducted in young, healthy, male volunteer subjects. Using a common protocol, 24-hour urine collections were analyzed for the renal tubular enzymes alanine aminopeptidase (AAP) and N-acetyl-beta-D-glucosaminidase (NAG), as well as for creatinine. Antimicrobial combinations studied included gentamicin plus placebo and gentamicin plus ticarcillin/clavulanate (protocol 1); and gentamicin plus placebo, gentamicin plus piperacillin, and gentamicin plus ceftazidime (protocol 2). The antimicrobial regimens were administered for 7 days. Eight subjects completed each treatment group. RESULTS: There were no significant differences between treatment groups with regard to urine creatinine excretion or serum gentamicin concentrations in either protocol. Enzymuria (AAP [p = 0.039] and NAG [p = 0.337]) was decreased in the gentamicin plus ticarcillin/clavulanate treatment compared with that in the gentamicin plus placebo treatment. Increased enzymuria, as indicated by increased urine concentrations of AAP and NAG, was observed in the gentamicin plus ceftazidime treatment (p < 0.05) compared with the other two treatments. CONCLUSIONS: Based on relative enzymuria, ticarcillin/clavulanate may be renal protective. Piperacillin neither potentiated nor ameliorated aminoglycoside-induced enzymuria. Since acute elevations in AAP and NAG reflect insults to the kidney, these studies suggest that ceftazidime may enhance aminoglycoside-induced renal injury. Piperacillin had no effect on enzymuria and would appear not to enhance or protect against aminoglycoside-induced renal injury.

Acetylglucosaminidase↗
PubMed1999

Comparison of five beta-lactam antibiotics against common nosocomial pathogens using the time above MIC at different creatinine clearances.

STUDY OBJECTIVE: To compare the time above the minimum inhibitory concentration (T>MIC) for five parenteral beta-lactam antibiotics against common nosocomial bacterial pathogens at different creatinine clearances (Clcr). INTERVENTIONS: Serum concentration-time profiles were simulated for cefepime, ceftazidime, piperacillin, piperacillin-tazobactam, and imipenem at Clcr ranging from 120-30 ml/minute. The MIC data for 90% of organisms (MIC90) were collected for Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Pseudomonas aeruginosa, and oxacillin-susceptible Staphylococcus aureus, and a weighted geometric mean MIC90 was calculated. The T>MIC was calculated as percentage of the dosing interval in which free concentrations exceeded the weighted geometric mean MIC90. A T>MIC of 70% or greater was considered desirable for all organisms except S. aureus (> or = 50%). MEASUREMENTS AND MAIN RESULTS: Cefepime 2 g every 12 hours (Clcr > or = 70 ml/min) and every 24 hours (Clcr < or = 60 ml/min) achieved desirable T>MIC for all Enterobacteriaceae and S. aureus at every Clcr. Imipenem 0.5 g achieved desirable T>MIC for E. coli, K. pneumoniae, C. freundii, and S. aureus at every Clcr. However, imipenem T>MIC was less than 70% for the following regimens and organisms: S. marcescens 0.5 g every 6 hours (Clcr > or = 90 ml/min), E. aerogenes 0.5 g every 6 hours (Clcr > or = 80 ml/min), E. cloacae 0.5 g every 6 hours (Clcr > or = 100 ml/min), S. marcescens 0.5 g every 8 hours (Clcr 60-70 ml/min), E. cloacae 0.5 g every 8 hours (Clcr 60-70 ml/min), and E. aerogenes 0.5 g every 8 hours (Clcr 50-70 ml/min). Ceftazidime 2 g every 8 hours (Clcr 60-100 ml/min) and every 12 hours (Clcr 40-50 ml/min) achieved desirable T>MIC for E. coli, K. pneumoniae, S. marcescens, and S. aureus only. At every dose and Clcr, piperacillintazobactam achieved desirable T>MIC for S. aureus but not for any Enterobacteriaceae at Clcr > 50 ml/minute. Piperacillin did not achieve desirable T>MIC for any organism, and none of the beta-lactams attained a T>MIC of 70% or above for P. aeruginosa at any Clcr. CONCLUSION: At every Clcr, cefepime achieved a desirable T>MIC for more nosocomial pathogens than any other beta-lactam evaluated. Based on pharmacodynamic data, cefepime is an appropriate empiric choice for treatment of nosocomial infections. However, when P. aeruginosa is a potential pathogen, empiric combination therapy should be considered.

Anti-Bacterial Agents↗