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PubMed1998

Comparison of strategies using cefpirome and ceftazidime for empiric treatment of pneumonia in intensive care patients. The Cefpirome Pneumonia Study Group.

In an international, multicenter, open-label, randomized comparative study, adult patients in intensive care units were enrolled to receive cefpirome intravenously at 2 g twice daily or ceftazidime intravenously at 2 g three times daily for the empiric treatment of pneumonia. Randomization was performed after a double stratification according to the investigator's initial choice of monotherapy or combination therapy and then on the basis of the severity of disease. The primary endpoint was the clinical response at the end of treatment in the intent-to-treat population. Data for all patients were reviewed by a blinded observer. Of the 400 enrolled patients, 201 received cefpirome (monotherapy, 56%) and 199 received ceftazidime (monotherapy, 51%). Pneumonia was hospital acquired for 75% of the patients. Clinical failures rates were 34 versus 36% (odds ratio = 0.922; upper bound of 90% confidence interval = 1.301) in the intent-to-treat analysis for cefpirome and ceftazidime, respectively. For the cefpirome and ceftazidime groups, there were 35 versus 30% clinical failures among monotherapy-stratified patients, respectively, and 34 versus 42% clinical failures among combination therapy-stratified patients, respectively. The rates of clinical failures in the per-protocol analysis were 38 and 42%, respectively. In the population of patients evaluable for bacteriologic efficacy, eradication or presumed eradication was obtained for 71% (172 of 241) and 70% (162 of 230) of the pathogens isolated from the patients receiving cefpirome and ceftazidime, respectively. The mortality rates within 2 weeks after the end of treatment were similar (cefpirome group, 31%; ceftazidime group, 26%), as were the percentages of patients with at least one treatment-related adverse event (17 and 19%, respectively). An empiric treatment strategy with cefpirome at 2 g twice daily is equivalent in terms of efficacy and tolerance to ceftazidime at 2 g three times daily for the treatment of pneumonia in patients in intensive care units.

Adult↗
PubMed1992

Prospective randomized phase II study of intravenous cefpirome 1g or 2g bd in the treatment of hospitalized patients with different infections. Cefpirome Study Group.

Two hundred and seventy-six hospitalized patients with severe infection (complicated UTI, pneumonia, skin and soft tissue infection or septicaemia) were randomly allocated to receive either 1g or 2g cefpirome bd. Two hundred and seventy-four patients were evaluable for tolerance, 210 for bacteriological efficacy. The two groups were similar in terms of underlying disease, age, sex, and general condition on admission. The overall clinical and bacteriological response rates were 97/103 (94%) and 68/76 (90%) respectively in the 1g group, compared with 102/107 (95%) and 67/71 (94%) in the 2g group. There was no significant difference between the treatment groups. Eighteen adverse events, possibly or probably drug related, were reported (7 in the 1g group, 11 in the 2g group). This resulted in discontinuation of therapy in four cases (two in each group). Fourteen of the adverse events were local (five receiving 1g, nine receiving 2g), mainly phlebitis or pain at the injection site. Thirteen patients died during the study period (up to 14 days after the last dose) but in no case was death attributed to cefpirome. A review of routine laboratory parameters revealed no abnormalities which could definitely be attributed to cefpirome although in four cases a relationship was considered possible; these included two increases in serum creatinine, one increase in SGPT, and one episode of neutropenia. Cefpirome administered as 1 or 2g twice daily was a well tolerated, effective agent for the treatment of severe sepsis in hospitalized patients.

Adolescent↗
PubMed1992

Influence of cefpirome on pharyngeal and faecal flora after single and multiple intravenous administrations of cefpirome to healthy volunteers.

The effect of single and multiple 2 g doses of i.v. cefpirome on pharyngeal and faecal flora was studied in ten male volunteers. There was no effect on pharyngeal flora. After a single dose, cefpirome had no effect on faecal flora but numbers of Escherichia coli were reduced below the detection limit during multiple dose treatment. No strains of Clostridium difficile were selected in this study and only a slight increase in the numbers of Candida spp. were found. Cefpirome, therefore, has little, if any, effect on faecal or pharyngeal flora.

Adult↗
PubMed1988

Synthesis and structure-activity relationships in the cefpirome series. III. 7 Alpha-methoxy and 7 alpha-formamido analogues of cefpirome.

7 alpha-Methoxy and 7 alpha-formamido derivatives of cefpirome (HR 810) have been synthesized and tested in comparison with cefpirome and some analogues 1 against aerobic and anaerobic bacteria. Cefpirome and analogues 1 have good activity against Gram-positive and only limited activity against Gram-negative anaerobic bacteria. 7 alpha-Methoxy derivatives 2 show only a slight improvement of activity against Gram-negative anaerobes and are less active against all aerobes. Introduction of the 7 alpha-formamido group (compounds 3) results in an overall loss of activity towards both aerobic and anaerobic bacteria.

Cephalosporins↗
PubMed1997

[Evaluation of bactericidal activity of cefpirome-aminoglycoside combination against Pseudomonas aeruginosa strains with intermediate sensitivity to cefpirome and in various phenotypes of beta-lactam resistance].

The bactericidal activity of cefpirome (CPO)-aminoglycoside (AG) combination was assessed by a kinetic time-kill method against 8 strains of Pseudomonas aeruginosa showing intermediate susceptibility to cefpirome (MICS: 8-32 mg/l). Six strains had an acquired beta-lactam resistance mechanism (moderate cephalosporinase hyperproduction, OXA-2 or PSE-1 enzyme production, non enzymatic resistance) and one strain was resistant to tobramycin (TOB). Antibiotic concentrations used for time-kill curves were 1/2, 1 and 2x MIC for cefpirome, 8 mg/l for tobramycin and 16 mg/l for amikacin (AKN). Bactericidal activity was defined as a (4 log10 reduction of the initial inoculum. At the concentrations used in this study, CPO was not bactericidal; AG were bactericidal in 3 to 24 hours. CPO-AG combination was bactericidal against all the strains with no secondary regrowth. For 7/8 strains, the combination of CPO with TOB and/or AKN was more rapidly bactericidal than the AG alone. In conclusion, despite an intermediate susceptibility against numerous strains of P. aeruginosa, the CPO-AG combination is bactericidal at concentrations achievable with standard dosing regimens in man.

Amikacin↗
PubMed1988

Synthesis and structure-activity relationships in the cefpirome series. II. Analogues of cefpirome with different 7-heteroarylacetamido and 3'-ammonium substituents.

The synthesis and antibacterial activity in vitro of 7-(2-heteroarylacetamido)-3-[(2,3- cyclopentenopyridinium)methyl]cephalosporins and of some related compounds with different ammonium functions in 3'-position are described. The 7-[5-amino-1,2,4-thiadiazol-3-yl] and the 7-[4-aminopyrimidin-2-yl] analogues of cefpirome and compounds with 3-aliphatic ammoniummethyl functions have excellent antibacterial activity. Cephalosporins with different N-heterocycles other than pyridine in 3'-position are less active than their 3-pyridiniummethyl analogues. Attachment of a pyridinium group to a cephem at C-3 via a thiomethyl or an aminomethyl bridge causes reduction of antibacterial activity.

Cephalosporins↗
PubMed1991

[Bacteriological, pharmacokinetic and clinical evaluations of cefpirome sulfate in the pediatric field. Pediatric Study Group of Cefpirome].

A research group was organized with the purpose of making basic and clinical studies on cefpirome sulfate (HR810, CPR), a newly developed cephalosporin antibiotic, in the pediatric field. Through meetings a joint research was done involving 19 key institutions and their related facilities throughout Japan. The obtained results are summarized as follows. 1. Antibacterial Activities Minimum inhibitory concentrations (MICs) were determined against 71 Gram-positive and 110 Gram-negative bacteria in the present clinical trials. CPR showed antibacterial activities 2-16 times higher than those of ceftazidime (CAZ) against Staphylococcus aureus and other Gram-positive bacteria including MRSA. Against Gram-negative bacteria, CPR showed a somewhat broad range of distribution in MIC against Branhamella catarrhalis, while the antibiotic inhibited the growth of all the strains of Escherichia coli and Haemophilus influenzae at concentrations no more than 0.10 and 0.20 micrograms/ml, respectively. 2. Blood Concentrations and Urinary Excretion Rates The pharmacokinetics in pediatric patients was investigated with a dose of 20 mg/kg in most cases via one shot intravenous injection or 30- and 60-minute intravenous drip infusion. Mean blood concentrations of CPR at 15 minutes after one shot intravenous injection of 10, 20, and 40 mg/kg were 51.2, 70.5, and 123.5 micrograms/ml, with half-lives of 1.21, 1.39, and 1.53 hours, respectively. Urinary excretion rates in 6 hours were 63.6, 66.0 and 71.6%, respectively for the 3 dose levels. After 30- and 60-minute intravenous drip infusions at the same dose, the pharmacokinetic parameters observed were similar to those obtained with one shot injections. 3. Concentration in the Cerebrospinal Fluid CPR penetrated well into the cerebrospinal fluid in patients with purulent meningitis and levels of 1.85-24.2 micrograms/ml 45-60 minutes were achieved after intravenous injection at a dose of 40-80 mg/kg, the penetration rate of CPR was at an intermediate degree compared with other cephalosporin antibiotics. 4. Clinical Results Clinical efficacies of CPR on infectious diseases were analyzed in 454 plus 3 cases which were complicated with other infectious diseases, hence totaling 457 cases out of 499 cases originally chosen for clinical evaluation. The remaining 45 cases were excluded from the clinical evaluation. As for the clinical efficacy, CPR was found to be effective (good or excellent) in 430 (94.1%) of the 457 cases. CPR was found to be effective in 243 (95.3%) of 255 cases for which causative bacteria were identified. The efficacy rate was 92.6% (187 of 202) in those cases in which causative bacteria were not identified.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1988

Activity of cefpirome (HR810) against Pseudomonas aeruginosa strains with characterised resistance mechanisms to beta-lactam antibiotics.

The activities of cefpirome, cefotaxime, ceftazidime and ceftriaxone were compared against laboratory and clinical strains of Pseudomonas aeruginosa. Isolates with well characterised resistance mechanisms were included. Against carbenicillin-susceptible isolates cefpirome was more active than cefotaxime and ceftriaxone, but less active than ceftazidime. The activity of all four cephalosporins was impaired against isolates that had increased intrinsic (i.e. non-beta-lactamase-mediated) carbenicillin resistance. However, cefpirome and ceftazidime, unlike the other compounds, remained active at less than 16 mg/l against such strains, whereas cefotaxime and ceftriaxone largely failed to do so. Cefpirome maintained full activity against most isolates with plasmid-mediated beta-lactamases, as did the other cephalosporins. Transconjugant studies indicated that only LCR-1 and PSE-2 enzymes could protect P. aeruginosa against cefpirome. Isolates with partial or total chromosomal beta-lactamase derepression were highly resistant to cefotaxime and ceftriaxone (MIC greater than 128 mg/l) but only those with total derepression were resistant (MIC 16-32 mg/l) to cefpirome and ceftazidime, while those with partial derepression were sensitive to 4-8 mg/l of the latter antibiotics. Comparison of cefpirome MICs for totally-derepressed P. aeruginosa and their enzyme-deficient mutants indicated that chromosomal beta-lactamase gave less protection against cefpirome than against other cephalosporins tested. Cefpirome was a weak inducer of class I beta-lactamases. Overall, therefore, cefpirome behaved similarly to ceftazidime against the different P. aeruginosa resistance types.

Anti-Bacterial Agents↗
PubMedDate not supplied

[In vitro antimicrobial activity of cefpirome compared to other broad-spectrum beta-lactam drugs against 804 clinical isolates from 9 Brazilian hospitals].

OBJECTIVE: To evaluate the in vitro activity of the fourth-generation cephalosporin cefpirome in comparison to that of ceftazidime, ceftriaxone, cefotaxime and imipenem in a multicenter study involving nine hospitals from six cities (four States). MATERIAL AND METHOD: A total of 804 isolates from patients hospitalized in either intensive care units or Oncology/Hematology units was evaluated. The isolates were collected between June and November of 1995, i.e. before cefpirome became commercially available in Brazil, and susceptibility tested by broth microdilution following the NCCLS procedures. All isolates resistant to cefpirome were retested by E-test. RESULTS: Against Enterobacteriaceae (n = 344), cefpirome demonstrated an activity 2 to 32-fold higher than that of the third-generation cephalosporins (TGCs) and similar to that of imipenem. The percentages of Enterobacteriaceae susceptible were: 88%, 69% and 96% for cefpirome, TGCs and imipenem, respectively. The cefpirome spectrum was greater or equal than that of imipenem against Citrobacter freundii, Enterobacter aerogenes, Morganella morganii and Serratia marcescens. Against Acinetobacter sp. (n = 77), cefpirome was slightly more active than ceftazidime; however, the percentages of isolates resistant to these compounds were high (84% and 88%, respectively). The activities of cefpirome, ceftazidime and imipenem were very similar against P. aeruginosa isolates (n = 128), with MIC50(mg/ml)/percent susceptible of 8/59%, 8/62% and 4/62% respectively. Against aerobic gram-positive bacteria, the cefpirome activity was 4 to 16-fold higher than that of TGCs but 2 to 8-fold lower than that of imipenem. CONCLUSION: The results suggest that, in Brazil, cefpirome has a spectrum of activity which is higher than that of the TGCs against aerobic gram-negative (Enterobacteriaceae and non-Enterobacteriaceae) and gram-positive bacteria and similar to that of imipenem against some Enterobacteriaceae species and P. aeruginosa.

Anti-Bacterial Agents↗
PubMed1993

Cross-susceptibility of cefpirome and four other beta-lactams against isolates from haematology/oncology and intensive care units. International Study Group.

A multi-centre in-vitro study (8625 isolates) was conducted in 13 countries between May and November, 1992 to determine both the current bacterial epidemiology in intensive care and haematology/oncology units and the cross-susceptibility of the organisms to cefpirome, ceftazidime, ceftriaxone, imipenem and piperacillin. Bacterial species with 20 or more isolates resistant to one of the six antibiotics were examined for their susceptibility to the beta-lactams. Cefpirome and imipenem had the smallest total numbers of isolates. Bacteria resistant to ceftazidime or ceftriaxone were often susceptible (> 50%) to cefpirome. Conversely, cefpirome resistant isolates were frequently resistant (> 90%) to ceftazidime and ceftriaxone. P. aeruginosa was an exception, exhibiting cross-resistance to all cephalosporins. beta-lactamase producing Enterobacter, Citrobacter and Klebsiella spp. were especially resistant to piperacillin and ceftazidime but not cefpirome or imipenem. Two-thirds or more of coagulase-negative staphylococci resistant to any single agent, including imipenem, maintained their susceptibility to cefpirome. Cross-class resistance was not exhibited by imipenem and cefpirome against ciprofloxacin resistant isolates but was more evident for piperacillin, ceftazidime and ceftriaxone. Cefpirome was more active than ceftazidime against bacteria resistant to both piperacillin and gentamicin, especially coagulase-negative staphylococci (76% vs. 6%) and Enterobacter spp. (56% vs. 21%). Many coagulase-negative staphylococci and Enterobacter spp. susceptible to cefpirome (50-89%). These results suggest that cefpirome has a potential clinical advantage against gram-positive and gram-negative bacteria resistant to other beta-lactams, including imipenem.

Anti-Bacterial Agents↗
PubMedDate not supplied

Bactericidal activity of cefpirome (HR 810) against 513 gram-negative bacteria isolated from blood of septicemic patients.

The profile of antibacterial activity of cefpirome was compared with that of nine other antimicrobial agents against 513 gram-negative bacteria isolated from septicemic patients. All strains were evaluated for their sensitivity by disc diffusion and broth dilution tests (MIC and MBC). Cefpirome was compared to cefazolin, cefuroxime, ceftazidime, ceftriaxone, aztreonam, imipenem, ticarcillin, tobramycin and ciprofloxacin. Among the five cephalosporins tested in this study, cefpirome was the most active against all isolates. The MIC50 and MIC90 of eight isolates of Acinetobacter calcoaceticus were 2 and 4 mg/l and those of 89 Pseudomonas aeruginosa were 2 and 8 mg/l, respectively. The MIC90 values of cefpirome for all other groups of bacteria were < or = 1 mg/l. The activity of cefpirome against gram-negative bacteria is at least as good as that of aztreonam and imipenem. The only drug showing a better profile of activity than cefpirome is ciprofloxacin. The scattergram of the 513 isolates for cefpirome MICs and inhibitory zones with the 30 micrograms disc, showed that only eight isolates were not susceptible to cefpirome. These data suggest that the in vitro activity of cefpirome is comparable to if not better than that of other beta-lactams and tobramycin.

Bacteremia↗
PubMed1992

Activity of cefpirome combined with beta-lactamase inhibitors and affinity for the penicillin-binding proteins of methicillin-resistant Staphylococcus aureus.

The susceptibility of 47 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) to cefpirome, ceftazidime and methicillin was determined with Isosensitest media, with/without 5% NaCl and incubation at 30 degrees, 37 degrees and 44 degrees C for 24 and 48 h. At 24 h the MIC50 of cefpirome was 8 mg/l compared to 64 mg/l ceftazidime; at 48 h this increased to 32 mg/l cefpirome. The addition of 10 mg/l clavulanic acid or sulbactam lowered the MIC of cefpirome (at 48 h) by greater than four-fold in 23% and 11% of the strains, respectively. Cefpirome had primary affinity for penicillin-binding protein (PBP) 1 and 2 in five MRSA and one methicillin-susceptible Staphylococcus aureus. PBP 2a was present in all MRSA and was not saturated by 64 mg/l cefpirome. Clavulanic acid at a concentration of 10 mg/l bound to PBP 2 by greater than 50% in all strains, and when combined with cefpirome, the density of PBP 2a was also reduced but not completely abolished. The data from this study suggests that the mechanism of synergy of a beta-lactamase inhibitor plus a cephalosporin for MRSA may be due to an additive effect against PBPs and not just inhibition of a beta-lactamase. No cefpirome-resistant mutants could be selected from a methicillin-susceptible Staphylococcus aureus, but mutants were selected from an MRSA (expressing homogeneous methicillin resistance) for which MICs of cefpirome were 8 to 32 mg/l.

Bacterial Proteins↗
PubMed1998

Use of in vitro models of haemofiltration and haemodiafiltration to estimate dosage regimens for critically ill patients prescribed cefpirome.

BACKGROUND: The physico-chemical properties of cefpirome (low protein binding, high water solubility and low molecular weight) suggest that it may be lost readily from the extracorporeal circulation of intensive care unit patients during continuous renal replacement therapy. METHOD: In order to make informed dosage recommendations for patients receiving artificial renal support, cefpirome loss from human blood has been quantified using in vitro models of continuous haemofiltration and haemodiafiltration. Cefpirome clearance was measured using three membrane types at varying ultrafiltrate (UFR) and dialysis flow rates (Qd). RESULTS: During haemofiltration cefpirome was found to cross hollow fibre polyamide (PA) and polyacrylonitrile (PAN) membranes with equal efficiency. The mean sieving coefficients (S) of both PA and PAN membranes were consistently high (> 0.7) when two different ultrafiltration rates were used. Changing the ultrafiltration rate or membrane type had no significant effect on the sieving coefficient of cefpirome but did result in an increase in cefpirome filter clearance (Fcl). Using the haemodiafiltration model, cefpirome penetrated PAN membranes (flat plate AN69S) more efficiently than hollow fibre PA membranes (FH66D). In each case, increasing the dialysis flow rate reduced the S-value. However, although increasing Qd was associated with a greater Fcl of cefpirome when PAN membranes were employed, no such relationship was found for the PA hollow fibre membrane. CONCLUSION: The information generated can be used to estimate a dosing regimen for intensive care patients prescribed cefpirome and receiving continuous renal replacement therapy.

Cephalosporins↗
PubMed1993

Cefpirome clinical pharmacokinetics.

Cefpirome is a new cephalosporin that exhibits similar in vitro potency to ceftazidime against Gram-negative organisms but has significantly greater in vitro potency against Gram-positive organisms. Cefpirome differs from cefotaxime in that a 3'-pyridinium moiety replaces the acetoxy moiety of cefotaxime. This structural change imparts greater beta-lactamase stability, increases the ability to penetrate the outer membrane of Gram-negative bacteria, and enhances activity against Gram-positive organisms. The pharmacokinetic properties of cefpirome are typical of cephalosporins. The drug can be administered by intravenous or intramuscular injection, but is not well absorbed after oral administration. Bioavailability following intramuscular injection exceeds 90%. Cefpirome exhibits low protein binding (approximately 10%) and has a volume of distribution similar to extracellular fluid volume. Cefpirome penetrates the prostate gland, lung, blister fluid, cerebrospinal fluid and peritoneal fluid, reaching concentrations that are similar to those achieved by other later generation cephalosporins. Approximately 80% of an intravenous dose is eliminated unchanged in the urine. No active metabolites of cefpirome have been identified. The elimination half-life of cefpirome is approximately 2 hours. Elimination appears to be primarily by glomerular filtration since the total clearance of cefpirome is approximately equal to creatinine clearance. The time during which drug concentrations exceed the minimum inhibitory concentration (MIC) represents the most clinically important pharmacodynamic parameter for beta-lactam agents. When cefpirome is administered at a dosage of 2g every 12 hours to patients without renal insufficiency [creatinine clearance 70 ml/min (4.2 L/h)], drug concentrations continuously remain above the MIC for pathogens with MIC values of < or = 2 micrograms/ml. With this dosage regimen, drug concentrations will be above the MIC for a pathogen with an MIC of 4 micrograms/ml for 80% of the dosage interval. The time above MIC for pathogens with an MIC of 8 micrograms/ml is only 60% of the dosage interval.

Animals↗
PubMed1988

[In vitro antibacterial activity of cefpirome in combination with 4 aminoglycosides and 2 fluoroquinolones].

Combinations of cefpirome with aminoglycosides (gentamicin, tobramycin, netilmicin, amikacin) and of cefpirome with fluorinated quinolones (pefloxacin, ofloxacin) were tested against 20 Enterobacteriaceae, 6 Pseudomonas aeruginosa, 6 Acinetobacter calcoaceticus, 6 group D Streptococci and 6 Staphylococcus aureus strains, susceptible, intermediate or resistant with a low level to these different compounds. Activity of combinations was evaluated using a broth microdilution checkerboard method and FIC indices determination. Combinations of cefpirome with aminoglycosides demonstrated a synergistic effect in 79.5% of cases, but a strong synergy (FIC less than or equal to 0.62) was observed in only 46% of cases. The higher rate of strong synergy concerned Enterobacteriaceae (50% of cases) and group D Streptococci (58.3%). Combination of cefpirome with gentamicin was the most active against Enterobacteriaceae and with a lower degree against P. aeruginosa, A. calcoaceticus and S. aureus. Combination of cefpirome with netilmicin was the best association against group D Streptococci. Combinations of cefpirome with fluorinated quinolones demonstrated frequently and additive (40.9%) or indifferent (36.3%) effect. When a synergistic effect was proved, it was always weak (FIC = 0.75). Combinations of two fluorinated quinolones with cefpirome gave similar results. No combination was antagonist. This study is a primary estimation of activity of cefpirome combined with other agents. It will be necessary to confirm these results against strains resistant with high level, especially against cefpirome, strains not discovered in clinical isolates at present.

4-Quinolones↗
PubMed1999

Pharmacokinetics of cefpirome during the posttraumatic systemic inflammatory response syndrome.

OBJECTIVE: To determine the pharmacokinetic parameters of cefpirome, a new so-called fourth-generation cephalosporin, in previously healthy trauma patients with posttraumatic systemic inflammatory response syndrome (SIRS) and to compare them to parameters obtained in matched, healthy volunteers. DESIGN: A prospective study. SETTING: 12-bed surgical intensive care unit in a university hospital. PATIENTS: 9 severe [Injury Severity Score, median (range) 29 (16-50)] trauma patients on mechanical ventilation with proven or suspected cefpirome-susceptible nosocomial infection, with no renal or hepatic failure, and healthy volunteers matched for age (+/- 5 years), sex, and body surface area (+/- 10%) were enrolled. All were men. INTERVENTIONS: Cefpirome (2 g twice daily) was continuously infused over a 0.5 h period alone or concomitantly with ciprofloxacin (400 mg over 1 h, twice daily). MEASUREMENTS AND MAIN RESULTS: Antibiotic concentrations in plasma were measured by high-performance liquid chromatography; their pharmacokinetic parameters were evaluated at 12 time points after the first drug administration using a noncompartmental model. Cefpirome pharmacokinetic parameters for the two groups were similar despite a wider variation for trauma patients. Specifically, the median (range) time during which the cefpirome concentration in plasma remained over 4 mg/l (corresponding to the French lower cutoff determining cefpirome susceptibility) was 9.5 (7- > 12) and 9 (8-12) h for trauma patients and healthy volunteers, respectively. In the group of five patients receiving combined antibiotic therapy, the interindividual variability of pharmacokinetics was wider for ciprofloxacin than for cefpirome. CONCLUSION: No major pharmacokinetic modification was noted when cefpirome was given to trauma patients with posttraumatic SIRS without significant organ failure, indicating that no dosage adjustment seems required in this population. However, larger studies including determination of antibiotic levels in tissues are warranted to confirm these results.

Adult↗
PubMed1990

Comparative therapy with cefpirome alone and in combination with rifampin and/or gentamicin against a disseminated Pseudomonas aeruginosa infection in leukopenic mice.

Treatment of disseminated Pseudomonas aeruginosa infection in leukopenic mice was evaluated using cefpirome alone and in combination with gentamicin and/or rifampin. Mice were made leukopenic with cyclophosphamide and infected through a skin incision with an inoculum of 1250 organisms (13 LD50). Antibiotics were administered subcutaneously for 48 h. Although the addition of cefpirome to gentamicin and/or rifampin improved survival significantly at 48 h compared with untreated controls (84.6%-100% vs. 38.5%), therapy with these combinations did not improve survival significantly from that achieved with cefpirome alone. Quantitative blood and tissue (liver, spleen, kidney, lung) cultures in mice treated with cefpirome alone or including rifampin were lower than in infected controls or groups receiving therapy that excluded cefpirome. Highest counts were observed in mice receiving cefpirome plus gentamicin. Except for the cefpirome plus gentamicin group, which demonstrated areas of acute tubular necrosis, the cefpirome group had less tissue pathology than infected controls.

Animals↗