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PubMed1986

[In vitro effect of piperacillin, amoxicillin, cefoxitin and metronidazole against obligate anaerobic bacteria].

The minimum inhibitory concentrations (MIC) of piperacillin and three other antibiotics (amoxicillin, cefoxitin, metronidazole) against 165 strains of obligate anaerobes isolated in hospitals in 1985 and 1986 were determined by the Wilkins-Chalgren agar medium dilution method. Among the 67 strains of Bacteroides fragilis, 98.5% were sensitive to piperacillin (MIC less than or equal to 128 mg/l), 100% were sensitive to metronidazole (MIC less than or equal to 4 mg/l), 11.9% were resistant to cefoxitin (MIC greater than 32 mg/l) and 46% were resistant to amoxicillin (MIC greater than 16 mg/l). The MIC50 was about 4 mg/l with piperacillin, 8 mg/l with cefoxitin and 0.5 mg/l with metronidazole. All 32 strains of Clostridium perfringens were sensitive to the 4 antibiotics tested, with an MIC50 of about 0.06 mg/l with piperacillin, 0.125 mg/l with amoxicillin and 0.5 mg/l with cefoxitin and metronidazole. All other strains of Clostridium spp. (33 in all) were sensitive to piperacillin and metronidazole; the MIC's were about 0.06 mg/l with piperacillin, 0.25 mg/l with amoxicillin and metronidazole and 0.5 mg/l with cefoxitin. Seven strains (C. innocuum 5, C. difficile 1, C. ramosum 1) were resistant to cefoxitin. All 33 strains of Peptostreptococcus and Peptococcus were sensitive to the 4 antibiotics tested. Although metronidazole still is the most effective of anti-anaerobes agents, piperacillin has proved to be effective against most anaerobic bacteria, including B. fragilis. It is clearly superior to amoxicillin and relatively superior to cefoxitin, notably against this species.

Amoxicillin↗
PubMed1986

[Bactericidal effect of piperacillin alone and combined].

The bactericidal activity of piperacillin was evaluated by the kill rate kinetics method. Piperacillin compared with amoxicillin, amdinocillin, mezlocillin, cefotaxime, ceftazidime and latamoxef. Against E. coli, piperacillin and antibiotics electively bound to penicillin-binding protein (PBP) 3 had the same, mainly time-dependent, bactericidal activity. Antibiotics bound to PBP 1 and 2 mainly have a dose-dependent activity. The bactericidal activity of piperacillin against E. coli was enhanced when the drug was combined with amoxicillin and amdinocillin; in contrast, the kill rate remained unmodified when piperacillin was combined with latamoxef. When the piperacillin-amikacin combination was tested against Pseudomonas aeruginosa, Enterobacter cloacae, Escherichia coli and Serratia marcescens, early synergism (5th hour), was weak, but after 24 hours piperacillin reduced the regrowth observed with the aminoglycoside, and synergism was much more pronounced irrespective of the species investigated.

Amikacin↗
PubMed1986

[Enzymologic aspect of piperacillin combinations].

Like all penicillins, piperacillin exhibits some susceptibility to beta-lactamases of the penicillinase type, including those produced by Staphylococcus aureus and the TEM, OXA and CARB enzymes isolated from Gram-negative bacilli. Piperacillin is very slightly hydrolyzed by cephalosporinases, which makes it similar to 3rd generation cephalosporins. When tested with Enterobacter cloacae GN 5797 and Pseudomonas aeruginosa NTC 8303, two strains which produce inducible cephalosporinases, piperacillin had moderate inductive activity compared to cefoxitin, a potent inducer. Induction was very low with Enterobacter, but the drug was slightly more sensitive to Pseudomonas. Inhibition of this type of beta-lactamase synthesis was very strong when piperacillin was combined with amikacin and weaker when it was combined with pefloxacin. The piperacillin-amikacin combination prevented the development of piperacillin-resistant mutants of Enterobacter and Pseudomonas and, probably, of all Gram-negative bacilli. In our tests, the piperacillin-pefloxacin combination was of interest only against Enterobacter, and probably against all enterobacteria, since Pseudomonas mutants that resist pefloxacin are fairly easily obtained in vitro.

Amikacin↗
PubMed1986

[Tissue concentrations of piperacillin in humans].

High serum levels and low degree of protein binding are the main factors which confer upon piperacillin a good distribution in tissues and biological fluids. In CSF, interstitial fluid, pleural and peritoneal fluids, piperacillin levels varied depending on the dose and on local inflammatory conditions; they reached high values ranging from 20 to 50 micrograms/ml corresponding to 18 to 25% of simultaneous serum levels. In bile, high and early levels of piperacillin were achieved, reaching about 1.200 to 3.200 micrograms/ml 100 min after i.v. injection of 2 or 4 g of the drug; in gallbladder wall more than 500 micrograms/g were measured. High tissue concentrations were found after 4 g i.v. of the drug in the renal cortex: 23 to 115 micrograms/g; in prostatic tissue: 70 micrograms/g; in bone: 15 micrograms/g; in cardiac tissue, especially myocardial tissue: 113 micrograms/g. In the female genital tract, the penetration of piperacillin was noticeable; levels of 15 to 45 micrograms/g were measured in uterus, ovary and salpinx: in contrast, placental transfer of piperacillin was limited. In the respiratory tract, the distribution of piperacillin was rapid, and concentrations of 12 to 30 micrograms/ml and 25 to 55 micrograms/g were found in bronchial secretions and bronchial mucosa respectively a 4 g i.v. dose. Studies of piperacillin distribution in the human body indicate that the drug reaches therapeutic levels in most tissues and biological fluids.

Ascitic Fluid↗
PubMed1987

Imipenem/cilastatin versus amikacin plus piperacillin in the treatment of infections in neutropenic patients: a prospective, randomized multi-clinic study.

In this open, controlled, randomized multi-clinic trial, monotherapy with imipenem/cilastatin was compared to amikacin plus piperacillin as empiric antibacterial therapy in 210 neutropenic cancer patients. Of patients randomized, 53 (25%) had bacteriologically documented infections and of those 30 had septicemia. A further 80 patients (38%) were evaluable for clinical efficacy but did not have documented infections. Seventy-seven patients (37%) were non-evaluable due to effective antibiotic treatment before the trial, early institution of other antibiotics during the trial, verified non-bacterial infections, no neutropenia or other reasons. There were no significant differences in terms of efficacy between imipenem/cilastatin and amikacin plus piperacillin but a consistent trend towards higher rates of clinical cure or improvement and of elimination of causative pathogens was noted in the imipenem/cilastatin group. In patients who were severely neutropenic (less than 0.1 x 10(9) granulocytes/l), similar cure rates were obtained in the two treatment groups--again with a tendency towards better results in the imipenem/cilastatin group. Among evaluable patients with septicemia, one patient in the imipenem/cilastatin group had persistent Staphylococcus aureus bacteremia during treatment. Five patients in the amikacin plus piperacillin group had persistent bacteremia during treatment; all but one (a Pseudomonas aeruginosa) caused by strains resistant to amikacin or piperacillin. Clinical and laboratory adverse effects were mild in the imipenem/cilastatin group although nausea was significantly more common than in the amikacin plus piperacillin group. Among patients on amikacin plus piperacillin, one died in renal failure, possibly related to treatment. Drug-related serious adverse events were reported in two additional amikacin plus piperacillin patients; one with drug fever and one with hearing loss. Microbiological adverse effects occurred in similar frequencies in the two groups. It is concluded that imipenem/cilastatin is a promising candidate for monotherapy of bacterial infections in neutropenic cancer patients.

Adolescent↗
PubMed1986

[Diffusion of piperacillin into bronchial secretions].

Piperacillin is a ureido-penicillin characterized by the presence of a piperazine group at the position 6 of the beta-lactam ring. This group confers a broader spectrum that includes Pseudomonas. In vitro studies have shown that piperacillin is active against clinical strains recovered from intensive care unit patients with severe lower respiratory tract infections. The purpose of our study was to investigate the usefulness of piperacillin in such patients by evaluating the drug's diffusion into bronchial secretions. A single 4 g dose of piperacillin was given intravenously over three minutes to each of 6 intensive care unit patients. Serum and bronchial secretion samples (obtained through a tracheal intubation or tracheostomy tube) were taken 1/2 hour, 2 h, 4 h and 6 h after the injection to evaluate piperacillin kinetics. Serum piperacillin concentrations were maximal 30 mn after the IV (mean value: 90.6 +/- 23.8 micrograms/ml) and thereafter fell gradually (mean value after 4 hours: 40.4 +/- 27.5 micrograms/ml). Peak concentrations in bronchial secretions were recorded at 2 hours (12.2 +/- 8.5 micrograms/ml); the mean residual value at 6 hours was 4.9 +/- 8.7 micrograms/ml. The diffusion ratio (ratio of bronchial secretion concentration to simultaneous serum concentration) was 15.5% to 24.5%. Our results show that the diffusion of piperacillin into bronchial secretions is outstanding and support the use of this drug in severe respiratory tract infections.

Adult↗
PubMedDate not supplied

Comparative review of two new wide-spectrum penicillins: mezlocillin and piperacillin.

The antimicrobial spectra, pharmacokinetics, tissue penetration, side effects, clinical trials and indications, dosage, and cost of mezlocillin (Mezlin) and piperacillin (Pipracil), two new semisynthetic beta-lactam penicillins, are reviewed. Both mezlocillin and piperacillin are active against a wider range of bacteria than previously available penicillins, but their spectra are not identical. Piperacillin is more active than mezlocillin against Pseudomonas aeruginosa; their activities against Klebsiella pneumoniae, Streptococcus faecalis, and Bacteroides fragilis are similar to one another. Neither drug is absorbed orally; both are well absorbed (60-70%) after i.m. injection. Following i.v. infusion or injection, both drugs distribute rapidly (distribution half-life = 10-20 min); neither is protein bound substantially. Both drugs are primarily excreted unchanged in the urine by glomerular filtration and tubular secretion. Elimination half-lives of both drugs are slightly prolonged in renal-failure patients. However, the half-life of mezlocillin in renal failure is longer then the half-life of piperacillin because of dose-dependent kinetics of mezlocillin at low glomecular filtration rates. Probenecid alters the disposition of both drugs. Both drugs are widely distributed throughout the body. Reported side effects are similar to those of other penicillins. Mezlocillin and piperacillin may be used to treat susceptible organisms causing the following conditions: complicated and uncomplicated urinary-tract infections, septicemia, uncomplicated gonococcal urethritis, and lower respiratory-tract, intra-abdominal, gynecologic, skin, and skin-structure infections. Piperacillin is also effective for bone and joint infections. Dosages of both antibiotics should be adjusted based on patients' clinical condition and renal status. Both agents are relatively expensive in comparison with older penicillins and cephalosporins; their daily costs are similar to third-generation cephalosporins, carbenicillin, and ticarcillin. The potential benefits of mezlocillin and piperacillin are in their extended in vitro spectra of activity and minimal toxicities. More comparative clinical trials are needed to support any claims of clinical superiority of these drugs over older, less expensive regimens.

Bacteria↗
PubMed2003

Incidence of neutropenia during treatment of bone-related infections with piperacillin-tazobactam.

Of 41 patients with bone-related infections who were treated for > or =10 days with piperacillin-tazobactam, 14 (34%) developed neutropenia. Cumulative doses of piperacillin administered to neutropenic patients were higher than those administered to nonneutropenic ones (330 vs. 237 g; P=.008), and an inverse correlation was detected between the absolute neutrophil count at the end of treatment and the cumulative dose of piperacillin (r=-0.47, P=.002). Moreover, the incidence of piperacillin-tazobactam-induced neutropenia increased with an increase in the cumulative dose of piperacillin: 0% of patients in the first quartile of cumulative piperacillin doses, 33.3% in the second quartile, 40% in the third quartile, and 66.7% in the fourth quartile.

Age Factors↗
PubMed2006

A randomized, open-label, multicenter comparative study of the efficacy and safety of piperacillin-tazobactam and cefepime for the empirical treatment of febrile neutropenic episodes in patients with hematologic malignancies.

BACKGROUND: The empirical treatment of febrile, neutropenic patients with cancer requires antibacterial regimens active against both gram-positive and gram-negative pathogens. This study was performed to demonstrate the noninferiority of monotherapy with piperacillin-tazobactam, compared with cefepime. METHODS: We conducted a randomized-controlled, open-label, multicenter clinical trial among high-risk patients from 34 university-affiliated tertiary care medical centers in the United States, Canada, and Australia who were undergoing treatment for leukemia or hematopoietic stem cell transplantation and were hospitalized for empirical treatment of febrile neutropenic episodes. Patients received piperacillin-tazobactam (4.5 g every 6 h) or cefepime (2 g every 8 h) intravenously. The primary outcome was success (defined by defervescence without treatment modification) at 72 h of treatment, end of treatment, and test of cure in the modified intent-to-treat analysis. Secondary outcomes included time to defervescence, microbiological efficacy, the additional use of glycopeptide antibiotics, emergence of resistant bacteria, and safety. RESULTS: For 528 subjects (265 received piperacillin-tazobactam and 263 received cefepime), success rates were 57.7% and 48.3%, respectively (P = .04) at the 72-h time point, 39.6% and 31.6% (P = .06) at end of treatment, and 26.8% and 20.5% (P = .11) at the test-of-cure visit. The analyses demonstrated noninferiority for piperacillin-tazobactam at all time points (P< or = .0001). Treatment with piperacillin-tazobactam was independently associated with treatment success in multivariate analysis (odds ratio, 1.65; 95% confidence interval, 1.04-2.64; P = .035). Both regimens were well tolerated. CONCLUSIONS: This study demonstrates the noninferiority and safety of piperacillin-tazobactam monotherapy, compared with cefepime, for the empirical treatment of high-risk febrile neutropenic patients with cancer.

Adolescent↗
PubMed2002

Ertapenem versus piperacillin-tazobactam for treatment of mixed anaerobic complicated intra-abdominal, complicated skin and skin structure, and acute pelvic infections.

BACKGROUND: Anaerobes are an important component of many serious, deep tissue infections, especially complicated intra-abdominal (IAI), complicated skin and skin structure (SSSI), and acute pelvic (PI) infections. This study compares the efficacy of ertapenem, 1 g once a day, in the treatment of adults with anaerobic IAI, SSSI, and PI to piperacillin-tazobactam, 3.375 g every 6 hours. METHODS: Three randomized, double-blind trials comparing ertapenem to piperacillin-tazobactam for treatment of IAI, SSSI, and PI were conducted. This subgroup analysis included 623 patients, whose baseline culture grew one or more anaerobic pathogens, from these three studies. RESULTS: Anaerobes most commonly isolated were Bacteroides fragilis group (IAI) and peptostreptococci (SSSI and PI). The median duration of ertapenem and piperacillin-tazobactam therapy, respectively, in these subgroups was 6 and 7 days for IAI, 7 and 8 days for SSSI, and 4 and 5 days for PI. Cure rates for all evaluable patients with anaerobic infection were 89.3% (242/271) for ertapenem and 85.9% (220/256) for piperacillin-tazobactam (95% CI for the difference, adjusting for infection, -2.6% to 9.3%), indicating that the two treatments were equivalent. Cure rates by infection, for ertapenem and piperacillin-tazobactam, respectively, were as follows: IAI, 86.4% (133/154) and 82.4% (117/142); SSSI, 84.4% (27/32) and 82.4% (28/34); PI, 96.5% (82/85) and 93.8% (75/80). The frequency and severity of drug-related adverse experiences were comparable in both treatment groups. CONCLUSION: In this subgroup analysis, ertapenem was as effective as piperacillin-tazobactam for treatment of adults with moderate to severe anaerobic IAI, SSSI, and PI, was generally well tolerated, and had a similar safety profile.

Abdomen↗
PubMed2003

Piperacillin-tazobactam versus ciprofloxacin plus amoxicillin in the treatment of infective episodes after liver transplantation.

An optimum antimicrobial regimen for bacterial infection after orthotopic liver transplantation has not been identified. In this prospective 4 year study of patients undergoing liver transplantation, patients were randomized to receive either piperacillin-tazobactam (112 patient episodes) or ciprofloxacin plus amoxicillin (105 patient episodes) for empirical treatment of infective episodes in the first 3 months after transplant. Metronidazole was added to the ciprofloxacin-amoxicillin regimen where anaerobic infection was suspected. Patient groups were comparable with respect to clinical, biochemical and haematological parameters. At the 72 h primary efficacy end-point, the overall response rate for the intention-to-treat group was 74/112 (66.1%) for piperacillin-tazobactam and 63/105 (60.0%) for ciprofloxacin plus amoxicillin (P=0.399); the corresponding figures for the per-protocol (PP) group were 73/82 (89.0%) (piperacillin-tazobactam) and 61/80 (76.3%) (ciprofloxacin plus amoxicillin) (P=0.038). At the end-of-study assessment, 58.9% of episodes in the piperacillin-tazobactam group had a successful clinical outcome, compared with 50.5% in the ciprofloxacin plus amoxicillin group (P=0.222); the corresponding figures for the PP group were 83.5% (piperacillin-tazobactam) and 68.8% (ciprofloxacin plus amoxicillin) (P=0.038). Staphylococci and aerobic Gram-negative bacilli were the predominant pathogens in both groups. Bacteria resistant to the study drugs were encountered, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium and multiply-resistant Klebsiella spp. Empirical monotherapy with piperacillin-tazobactam is an effective treatment for infective episodes in liver transplant patients.

Adolescent↗
PubMed1995

Piperacillin-tazobactam plus amikacin versus ceftazidime plus amikacin as empiric therapy for fever in granulocytopenic patients with cancer. The International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer.

Gram-positive bacteria have become the predominant infecting organisms in granulocytopenic cancer patients. Empiric antibiotic regimens used in febrile neutropenic patients often include an extended-spectrum cephalosporin, but the response to therapy in gram-positive coccal bacteremia has been unsatisfactory. Thus, new antibiotics with better activity against gram-positive bacteria should be tested. The objective of this prospective randomized controlled study was to evaluate and compare the efficacy and tolerance of piperacillintazobactam plus amikacin with that of ceftazidime plus amikacin, the standard regimen of the International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer, in the empiric treatment of febrile granulocytopenic cancer patients. A total of 858 episodes were eligible for this study, and 706 episodes were assessable for efficacy. The antibiotic treatment was successful in 210 (61%) of 342 episodes in the piperacillin-tazobactam-amikacin group compared with 196 (54%) of 364 episodes treated with ceftazidime plus amikacin (P = 0.05). The time to defervescence was significantly shorter (P = 0.01) and the time to failure was significantly longer (P = 0.02) in the piperacillin-tazobactam-amikacin group. A significant difference in response to bacteremic infections between the two patient groups was found: piperacillin-tazobactam plus amikacin was successful in 40 of 80 episodes (50%), and ceftazidime plus amikacin was successful in 35 of 101 episodes (35%) (P = 0.05). A multivariate analysis showed that the probability of failure was significantly greater with ceftazidime plus amikacin than with piperacillin-tazobactam plus amikacin (P = 0.02). This trial suggests that piperacillin-tazobactam plus amikacin is more effective than ceftazidime plus amikacin for the empiric treatment of fever and bacteremia in granulocytopenic cancer patients. Although cutaneous reaction was more frequently associated with piperacillin-tazobactam plus amikacin than with ceftazidime-amikacin, this unwanted effect was relatively mild and its incidence was comparable to that of other penicillin compounds.

Adolescent↗
PubMed1998

[Evaluation of in vitro susceptibility of hospital bacterial isolates to piperacillin and tazocin (piperacillin/tazobactam].

Due to increasing frequency of infections caused by pathogens that are resistant to beta-lactam antibiotics, combinations of such antibiotics and beta-lactamase inhibitors were introduced into therapy in last few years. Tazobactam is the most potent beta-lactamase inhibitor. The purpose of the study was to evaluate in vitro susceptibility to piperacillin and piperacillin with tazobactam of 256 isolates cultured from biological samples obtained from 203 patients. The biological materials obtained were as follows: urine (44.9%), post-operative and post-traumatic wound swabs (27.3%), BAL (12.1%), blood (6.6%), drain swabs and other (5.5%). The isolates predominantly found were Escherichia coli (22.3%), Pseudomonas aeruginosa (16.0%), Staphylococcus aureus MSSA (13.7%), Proteus mirabilis (11.7%) and other. There were 95.5% of strains found susceptible to piperacillin with tazobactam and only 4.3% resistant ones. On the other hand, piperacillin only susceptible strains were 59.4% and resistant ones in 40.6%. Great differences in susceptibility to examined antimicrobial agents were observed in Enterobacteriaceae family and Staphylococcus (MSS) genus. There were no differences in susceptibility to piperacillin and tazobactam and piperacillin alone in anaerobic Enterobacteriaceae strains and non-fermenting Gram-negative bacilli.

Body Fluids↗
PubMed2005

Quantitation and stability of piperacillin and tazobactam in plasma and ultrafiltrate from patients undergoing continuous venovenous hemofiltration by HPLC.

Simple and reproducible HPLC methods for the determination of piperacillin and tazobactam have been developed and a complete stability study carried out. The method for piperacillin plasma samples consisted of protein precipitation with methanol using penicillin G as internal standard. No sample preparation was needed for ultrafiltrate samples. Tazobactam sample preparation involved protein precipitation with acetonitrile and the removal of lipids with dichloromethane. Piperacillin separation was performed on a microBondapack C(18) column (300 x 3.9, 10 microm) and tazobactam on a Novapack C(18) column (150 x 3.9, 4 microm) with UV detection set at 229 and 225 nm, respectively. The mobile phase consisted of phosphate buffer-acetonitrile, delivered at 1.5 mL[sol ]min. Calibration curves determination coefficients were >or=0.999 and response factors CV% < 5%. Intra- and inter-assay precision and accuracy of the quality control and limit of quantification were satisfactory. Plasma and ultrafiltrate samples were stable at -20 and -80 degrees C for 2 months and after three freeze-thaw cycles. In the chromatographic rack, tazobactam ultrafiltrate samples were stable for 24 h and plasma samples for 12 h, piperacillin ultrafiltrate samples for 8 h, but plasma samples for only 4 h. Storage of piperacillin samples at 4 degrees C until analysis is recommended. Piperacillin was stable in the presence of tazobactam.

Anti-Bacterial Agents↗
PubMedDate not supplied

The role of piperacillin therapy in pulmonary exacerbations of cystic fibrosis: a controlled study.

Piperacillin was evaluated as an antipseudomonas antibiotic in a double-blind controlled trial involving 18 pulmonary exacerbations of cystic fibrosis. Standard antibiotic treatment (flucloxacillin plus tobramycin) was compared with standard treatment plus intravenous piperacillin administered according to two regimens. No added benefit from piperacillin was demonstrable on the basis of improvement in symptoms, physical signs, weight gain, pulmonary function tests, radiologic signs, or sputum Pseudomonas bacterial counts. Some patients experienced sensitivity reactions to piperacillin. In vitro, piperacillin was a potent antibiotic against all beta-lactamase-producing mucoid strains of Pseudomonas aeruginosa; however, in spite of the fact that adequate serum antibiotic concentrations were achieved, sputum bacterial counts did not correlate with either the clinical status or the use of piperacillin therapy.

Adolescent↗
PubMedDate not supplied

The effect of piperacillin prophylaxis on the colonic microflora In patients undergoing colorectal surgery.

Piperacillin was given parenterally in doses of 4 g every 8 h for two days to 20 patients undergoing colorectal surgery. A series of serum and fecal specimens were taken to analyse piperacillin concentrations. Tissue samples from the gut wall were taken during surgery. The maximum serum concentrations during surgery were reached 15 min after piperacillin administration. On Day 0 the mean half-life was 1.9 h and the mean area under the serum concentration curve was 536.8 mg/l. The piperacillin concentrations in the tissue samples ranged from 4.2 to 103.5 mg/kg. The tissue/serum ratio was 0.45. The piperacillin concentrations in the fecal samples ranged from not detectable to 101.2 mg/kg. Fecal samples were also collected during the investigation period for the cultivation of aerobic and anaerobic bacteria. Of the aerobic bacteria, enterococci, streptococci and enterobacteria decreased in on fourth of the patients during the prophylaxis period. Anaerobic bacteria, e. g. cocci, gram-positive rods, fusobacteria and bacteroides, decreased in two thirds of the patients during the same period. After the piperacillin administration period, the aerobic and anaerobic colon microflora returned to the pre-treatment pattern in most patients. Postoperative infections due to Escherichia coli, Morganella morganii, Bacteroides fragilis, peptococci and peptostreptococci occurred in two patients.

Aged↗
PubMed2002

Piperacillin-induced magnesium and potassium loss in intensive care unit patients.

OBJECTIVE: Broad spectrum penicillins such as piperacillin are used extensively in the intensive care unit (ICU) because of their wide bacterial spectrum and low level of toxicity. Although some cases of interstitial nephritis induced by piperacillin have been reported, this problem is thought to be rare. However, in view of the large number of other risk factors for renal disorders that are frequently present in ICU patients, we speculated that ICU patients might be more at risk for renal side effects. We therefore decided to measure serum electrolyte levels in patients before and after piperacillin administration. DESIGN: Prospective observational study. SETTING: University teaching hospital. PATIENTS AND PARTICIPANTS: Forty-three consecutive patients with normal renal function treated with piperacillin; 40 patients treated with other antibiotics. RESULTS: Serum levels of magnesium (Mg), potassium (K) and, to a lesser degree, calcium (Ca) decreased significantly in patients treated with piperacillin, but not in patients treated with other antibiotics ( p<0.01). This decrease was especially pronounced in a subgroup of patients concurrently treated with furosemide. CONCLUSIONS: We conclude that treatment with piperacillin may cause or aggravate electrolyte disorders and tubular dysfunction in ICU patients even when serum creatinine levels remain normal.

Adult↗
PubMed2006

Impact of piperacillin resistance on the outcome of Pseudomonas ventilator-associated pneumonia.

BACKGROUND: The impact of antibiotic resistance on the outcome of infections due to Gram-negative bacilli, especially Pseudomonas, remains highly controversial. STUDY OBJECTIVE, DESIGN, AND PATIENTS: We evaluated the impact of piperacillin resistance on the outcomes of Pseudomonas aeruginosa ventilator-associated pneumonia (VAP) for patients who had received appropriate empiric antibiotics before enrollment in the PNEUMA trial, a multicenter randomized study comparing 8 vs 15 days of antibiotics. RESULTS: Despite similar characteristics at intensive care unit (ICU) admission, patients infected with piperacillin-resistant Pseudomonas strains were more acutely ill at VAP onset and had a higher 28-day mortality rate (37 vs 19%; P = 0.04) than those with piperacillin-susceptible Pseudomonas VAP. Factors associated with 28-day mortality retained by multivariable analysis were: age (OR: 1.07; 95% CI: 1.03-1.12); female gender (OR: 4.00; 95% CI: 1.41-11.11); severe underlying comorbidities (OR: 2.73; 95% CI: 1.02-7.33); and SOFA score (OR: 1.17; 95% CI: 1.03-1.32), but piperacillin resistance did not reach statistical significance (OR: 2.00; 95% CI: 0.72-5.61). The VAP recurrence rates, either superinfection or relapse, and durations of mechanical ventilation and ICU stay did not differ as a function of Pseudomonas-resistance status. CONCLUSIONS: For patients with Pseudomonas VAP benefiting from appropriate empiric antibiotics, piperacillin resistance was associated with increased disease severity at VAP onset and higher 28-day crude mortality; however, after controlling for confounders, piperacillin-resistance was no longer significantly associated with 28-day mortality. The VAP recurrence rates and durations of ICU stay and mechanical ventilation did not differ for susceptible and resistant strains.

Aged↗