Pharmacokinetics of cefoperazone in full-term and premature neonates

Rosenfeld, Warren; Evans, Hugh E.; Batheja, Raman; Jhaveri, Ramesh; Vohra, Kiran; Khan, Aisha

doi:10.1128/aac.23.6.866

Cited by 21 publications

(12 citation statements)

References 7 publications

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“…In vivo, BMY-28142 produced significantly greater bactericidal titers in blood and CSF than did cefotaxime and penicillin G. It should be noted that the mean concentration of BMY-28142 in serum at 7 to 8 h after administration was still at approximately 14% of the 1-to 2-h level, suggesting a slow decay in vivo. This finding of presumed longer half-life is similar to half-lives observed with ceftriaxone and cefoperazone (3,11,13).…”

Section: Resultssupporting

confidence: 71%

Efficacy of BMY-28142 in experimental bacteremia and meningitis caused by Escherichia coli and group B streptococci

Kim¹,

Bayer²

1985

Antimicrob Agents Chemother

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We evaluated the activity of BMY-28142 against a Kl E. coli strain and a type III group B streptococcal strain in vitro and in vivo and compared the results with those of cefotaxime and penicillin G, respectively. In vitro, the MICs and MBCs of BMY-28142 were close to those of cefotaxime (s2-fold difference) for E. coli and fourfold less than those of penicillin G for group B streptococci. In vivo studies with an experimental bacteremia and meningitis model in newborn rats revealed that the mean penetration of BMY-28142 into the cerebrospinal fluid was 15% that of concomitant levels in serum and that significantly greater bactericidal titers were achieved in blood and cerebrospinal fluid for both test organisms with BMY-28142 than with cefotaxime and penicillin G. However, the overall efficacy of BMY-28142 was similar to that of cefotaxime for the E. coli infection and that of penicillin G for the group B streptococcal infection. This was shown by similar rates of bacterial clearance .from blood and cerebrospinal fluid and similar mortality rates. These findings indicate that the activity of BMY-28142 is bactericidal in vitro and in vivo against E. coli and group B streptococci, suggesting that this agent may be a suitable alternative for the therapy of E. coli and group B streptococcal bacteremia and meningitis.Because of the significant morbidity and mortality associated with neonatal bacterial infections, particularly due to E. coli and group B streptococci (GBS), many new beta-lactam antibiotics with expanded in vitro spectra have generated considerable enthusiasm for studies of their activities in vivo.BMY-28142 is a novel cephalosporin with potent in vitro activity against most aerobic and facultatively anaerobic gram-positive and gram-negative organisms (1,4,5).This study was performed to evaluate the activity of BMY-28142 in vitro and in vivo against Escherichia coli and GBS, the two most common bacterial pathogens in newborn infants (14). The results were compared with those of cefotaxime for E. coli and those of penicillin G for GBS. MATERIALS AND METHODSOrganisms. A serum-resistant E. coli Kl strain (C5) and a type III GBS strain (K79) were used in this study. Both organisms were isolated from the cerebrospinal fluid (CSF) of newborn infants with meningitis (6-8).In vitro studies. MICs and MBCs were measured in Mueller-Hinton broth (Difco Laboratories, Detroit, Mich.) by the standard macrobroth dilution method (17). The antimicrobial agents tested were BMY-28142 (Bristol Laboratories, Syracuse, N.Y.) for both E. coli and GBS, cefotaxime sodium (Hoechst-Roussel Pharmaceuticals, Somerville, N.J.) for E. coli, and potassium penicillin G (Bristol) for GBS. Antimicrobial agent solutions were diluted serially twofold from 4 to 0.008 ,ug/ml in Mueller-Hinton broth. An inoculum of approximately 2 x 105 CFU/ml of the E. coli or GBS strain was prepared as described previously from late-logarithmic-phase cultures (6, 7). Equal volumes (0.5 ml) of antibiotic and bacterial dilutions were mixed and incubated at 37°...

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Section: Resultssupporting

confidence: 71%

Efficacy of BMY-28142 in experimental bacteremia and meningitis caused by Escherichia coli and group B streptococci

Kim¹,

Bayer²

1985

Antimicrob Agents Chemother

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“…Levels in blood during 15 to 30 min after the dose were 12 to 100 times the MIC for 90% of the strains of common pathogens, including Escherichia coli and Proteus mirabilis (9) and 17 to 30 times more than necessary to inhibit 90% of the strains of Staphylococcus aureus (9). Levels in blood observed in this study were lower than those reported in 1-to 2-day-old infants, including premature infants (11). This difference may be due to a larger dose (50 mg/kg) and also immature renal and liver functions at that age, as CPZ is excreted both by the renal and biliary tracts.…”

contrasting

confidence: 54%

“…In the pediatric age group, including neonates, the drug has not been well studied. Single doses administered during the first week of life were safe and revealed a prolonged half-life (11). We now report the pharmacokinetics of this drug in infants older than 2 weeks.…”

mentioning

confidence: 99%

Pharmacokinetic evaluation of cefoperazone in infants

Varghese¹,

Khan²,

Kumar³

et al. 1985

Antimicrob Agents Chemother

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The pharmacokinetics of cefoperazone were evaluated in 25 infants (mean age, 26 days) after intramuscular and intravenous routes of administration. The levels in blood that were achieved were severalfold higher than those required to inhibit common pathogens. The mean half-life of 240 min was one-half of that observed in 1-to 2-day-old infants but about twice that seen in adults. Further evaluation is needed to study the efficacy of the drug in infants and children.Cefoperazone (CPZ) is a new semisynthetic third-generation cephalosporin antibiotic with a broad antimicrobial spectrum which includes Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus aureus, ampicillin-resistant Haemophilus influenzae, and Streptococcus agalactiae or group B streptococcus in addition to other common gramnegative and gram-positive pathogens (3,7,9). It has a longer half-life than other third-generation cephalosporins (8) and crosses the blood brain barrier in therapeutic concentrations (4, 5). Studies in adults have revealed CPZ to be useful in various bacterial infections (6, 10), including meningitis (5). In the pediatric age group, including neonates, the drug has not been well studied. Single doses administered during the first week of life were safe and revealed a prolonged half-life (11). We now report the pharmacokinetics of this drug in infants older than 2 weeks.( Table 1). An additional specimen was collected just before the dose in the i.m. groups and at the end of infusion in the i.v. groups. Serum was separated immediately and kept frozen at -20°C. The specimens were shipped in dry ice within 2 to 6 weeks of collection to the University of Tennessee, where they were received in a frozen state. The concentration of CPZ was determined by high-performance liquid chromatography by using a Water's Associates HPLC system with a model 440, 254-fixed-wave-length detector and a Bondapak C-18 column (10 ,um by 13.9 mm by 30 cm). Samples were run isocratically with hydrochlorothiazide as an internal standard. The serum half-life (tl,2) and volume of distribution were determined by plotting the serum concentration against time by using a semilogarithmic graph as previously described (11). The t, was calculated when the level in blood was declining exponentially during the elimination phase by utilizing the formula tl,2 = In 21k where k is the elimination rate constant,

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“…In the preterm, t 1/2 is longer than in full-term infants as these antibiotics are mainly eliminated by renal route and the excretory renal function increases with prenatal and postnatal development. This has been observed for azlocillin [24], ticarcillin [29], cefotaxime [35], ceftazidime [42], cefoperazone [59], gentamicin [81] and amikacin [98]. Cl has a reverse trend, it is lower in preterm than in full-term infants.…”

Section: Discussionmentioning

confidence: 90%

Clinical Pharmacokinetics of Penicillins, Cephalosporins and Aminoglycosides in the Neonate: A Review

Pacifici

2010

Pharmaceuticals

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Bacterial infections are common in the neonates and are a major cause of morbidity and mortality. Sixty percent of preterm infants admitted to neonatal intensive care units received at least one antibiotic during the first week of life. Penicillins, aminoglycosides and cephalosporins comprised 53, 43 and 16%, respectively. Kinetic parameters such as the half-life (t1/2), clearance (Cl), and volume of distribution (Vd) change with development, so the kinetics of penicillins, cephalosporins and aminoglycosides need to be studied in order to optimise therapy with these drugs. The aim of this study is to review the pharmacokinetics of penicillins, cephalosporins and aminoglycosides in the neonate in a single article in order to provide a critical analysis of the literature and thus provide a useful tool in the hands of physicians. The bibliographic search was performed electronically using PubMed, as the search engine, until February 2nd, 2010. Medline search terms were as follows: pharmacokinetics AND (penicillins OR cephalosporins OR aminoglycosides) AND infant, newborn, limiting to humans. Penicillins, cephalosporins and aminoglycosides are fairly water soluble and are mainly eliminated by the kidneys. The maturation of the kidneys governs the pharmacokinetics of penicillins, cephalosporins and aminoglycosides in the neonate. The renal excretory function is reduced in preterms compared to term infants and Cl of these drugs is reduced in premature infants. Gestational and postnatal ages are important factors in the maturation of the neonate and, as these ages proceed, Cl of penicillins, cephalosporins and aminoglycosides increases. Cl and t1/2 are influenced by development and this must be taken into consideration when planning a dosage regimen with these drugs. More pharmacokinetic studies are required to ensure that the dose recommended for the treatment of sepsis in the neonate is evidence based.

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Pharmacokinetics of cefoperazone in full-term and premature neonates

Cited by 21 publications

References 7 publications

Efficacy of BMY-28142 in experimental bacteremia and meningitis caused by Escherichia coli and group B streptococci

Efficacy of BMY-28142 in experimental bacteremia and meningitis caused by Escherichia coli and group B streptococci

Pharmacokinetic evaluation of cefoperazone in infants

Clinical Pharmacokinetics of Penicillins, Cephalosporins and Aminoglycosides in the Neonate: A Review

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