Antimicrob Agents Chemother, 1985 Oct, 28(4), 544 - 7 Pharmacokinetics of cefmetazole administered intramuscularly and intravenously to healthy adults; Rodriguez-Barbero J et al.; The pharmacokinetics of cefmetazole, a new parenteral cephalosporin, administered intravenously and intramuscularly at a dose of 30 mg/kg to two groups of seven healthy volunteers were studied . Concentrations in serum were monitored over 8 h by a high-pressure liquid chromatography technique . The plasma concentration-time data were statistically fitted to a biexponential equation for both administration routes, and the data were analyzed by a two- and one-compartment kinetic model, respectively . For the dose range and the administration routes used, the pharmacokinetics of cefmetazole proved to be essentially linear, with clearances from plasma ranging between 3.8 and 12.5 liters/h . The mean maximum concentration in plasma after intramuscular administration of the drug was 90.1 micrograms/ml at 0.7 h . The elimination half-life, about 1.3 h, did not show statistically significant differences for the two routes of administration studied. Jpn J Antibiot, 1985 Sep, 38(9), 2397 - 401 {Clinical studies on cefpiramide}; Fukuda T; A new cephalosporin, cefpiramide was administered to 12 patients with gynecological infections and the clinical effects obtained were good in 11 cases and poor in 1 (effective ratio: 91.7%) . No side effects were observed except for eruption in 1 case, however, the relationship between the drug and eruption was unknown . No abnormalities were observed in hematological, hepatic and renal tests. J Nat Prod, 1985 Sep-Oct, 48(5), 708 - 24 The stereochemical fate of chiral-methyl valines in cephalosporin C biosynthesis; Townsend CA; Samples of D,L-valine bearing chiral-methyl groups in the 3-pro(R) and 3-pro(S) positions have been prepared to investigate the stereochemical course of the alpha-ketoglutarate-dependent dioxygenase-catalyzed ring expansion of penicillin N to deacetoxycephalosporin C and the 3'-hydroxylation of the latter to deacetylcephalosporin C, respectively . The orientation of tritium at the diastereotopic C-2 methylene positions of cephalosporin C has been determined in a kinetic assay involving its conversion to N-t-butoxycarbonyldeacetylcephalosporin C-1beta-oxide and monitoring the loss of tritium at constant pH, ionic strength, and temperature . Control experiments are described that demonstrate the validity of treating tritium losses from the methylene as parallel pseudo-first-order processes . An equal distribution to tritium between the two C-2 loci was observed accompanied by a large intrinsic isotope effect . It was concluded that the ring expansion takes place with complete epimerization . Parallel stereochemical examination of the cephem 3'-hydroxylation was carried out by oxidative degradation of cephalosporin C to obtain samples of acetylglycolate . After saponification to glycolate, these specimens were assayed with glycolate oxidase to reveal the overall stereochemical course of hydroxylation as retention. Drug Intell Clin Pharm, 1985 Sep, 19(9), 677 - 9 The lack of inactivation of tobramycin by cefazolin, cefamandole, and moxalactam in vitro; Earp CM et al.; We examined the effects of mixing tobramycin with three cephalosporins, cefazolin, cefamandole, and moxalactam . Each cephalosporin was prepared from standard powder and diluted with human serum to concentrations of 50, 250, and 500 micrograms/ml and added to 10 micrograms/ml of tobramycin in human serum . Temperature environments of 4 degrees C (refrigeration), 24 degrees C (room temperature), and 37 degrees C (body temperature) were used and sampled at 0 hours (control), and at 8, 24, and 48 hours . The results indicated no inactivation of tobramycin by any of the cephalosporins, regardless of temperature, concentration, or contact time . These results indicate that significant inactivation of tobramycin does not occur when it is combined in vitro with moxalactam, cefamandole, or cefazolin. Anal Biochem, 1985 Aug 15, 149(1), 105 - 10 Determination by high-performance liquid chromatography of some compounds involved in the biosynthesis of penicillin and cephalosporin; Usher JJ et al.; A sensitive and convenient method for the simultaneous determination of several of the compounds involved in the biosynthesis of penicillin and cephalosporin is described . The method involves derivatization with a chiral fluorogen (o-phthaldialdehyde with an optically active thiol N-acetyl-L-cysteine), followed by high-performance liquid chromatography on a reverse-phase column as described by Aswad (D . W . Aswad, 1984, Anal . Biochem . 137, 405-409) . With an analysis time of 1 h it was possible to determine simultaneously most of the common L-amino acids, L- and D-alpha-aminoadipic acid, L- and D-valine, delta-(L-alpha-aminoadipyl)-L-cysteine (AC), delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV), glutathione, isopenicillin N, penicillin N, desacetoxycephalosporin C, desacetylcephalosporin C, and cephalosporin C . Using o-phthaldialdehyde alone it was possible to determine specifically the thiol-containing peptides AC, ACV, and glutathione. Jpn J Antibiot, 1985 Aug, 38(8), 2342 - 7 {Clinical effect of cefpiramide against infectious diseases in obstetrics and gynecology}; Chimura T et al.; Clinical study on cefpiramide (CPM, SM-1652), a new cephalosporin antibiotic, was carried out and the following results were obtained . CPM was intravenously administrated at a daily dose of 2 g to 8 cases including 2 cases with intrauterine infection, 3 cases with adnexitis, 2 cases with intrapelvic infection and 1 case with external genital infection . All cases responded to the drug, and marked response was seen in 2 cases, moderate response in 6 cases . Neither side effects nor abnormal values in clinical laboratory findings attributable to the drug were seen. J Antibiot (Tokyo), 1985 Aug, 38(8), 1088 - 95 Mechanism of renal excretion of FK027 in dogs and rabbits; Sakamoto H et al.; The mechanism of renal excretion of FK027, a new oral cephalosporin, was investigated in dogs and rabbits . In dogs, FK027 was mainly cleared by glomerular filtration, and approximately 50% of the filtered drug was reabsorbed through the proximal tubules . This tubular reabsorption and a high binding ratio to serum protein lead to the exceptionally long serum half-life of the drug . The facts that the clearance ratio of FK027 declined slightly from 58.0 to 49.2% by the addition of probenecid, and that the effect of probenecid was less marked in the stop-flow study, along with no significant change in serum half-life, may account for the scarcely detectable secretion from the renal tubules . In rabbits, the addition of probenecid caused a decrease of the clearance ratio of FK027, disappearance of FK027 peak in the stop-flow study, and extended the serum half-life . These facts are evidence that FK027 is excreted by both tubular secretion and glomerular filtration in rabbits. South Med J, 1985 Aug, 78(8), 962 - 6 Cephalosporins for surgical prophylaxis: computer projections of intraoperative availability; Nix DE et al.; Cephalosporin antibiotics are the most frequently used agents for surgical prophylaxis . Within this class are considerable pharmacokinetic variations that could have significant implications . We used a computer simulation of cephalosporin serum levels to describe concentrations achieved and maintained intraoperatively when the agents are given intravenously "on call" to the operating room or with induction of anesthesia . Intraoperative serum concentrations fall below 1 microgram/ml if an operation lasts longer than 2.3, 2.7, 3.8, or 4.0 hours when cephalothin, cephapirin, cefamandole, or cefoxitin, respectively, is given in usual doses upon induction of anesthesia . When the same agents are given intravenously on call to the operating room, intraoperative serum concentrations fall below 1 microgram/ml for operations lasting longer than 1.1, 1.5, 2.6, or 2.8 hours, respectively . If cephalothin, cephapirin, cefamandole, or cefoxitin is used, it should be given at induction of anesthesia to provide maximal intraoperative serum concentrations . The longer half-life of cefazolin, ceforanide, cefonicid, and cefuroxime is a potential advantage because serum concentrations of these agents are well above 1 microgram/ml for as long as eight to 22 hours even after on-call administration. Br J Surg, 1985 Aug, 72(8), 665 - 7 Vitamin K requirements in patients receiving total parenteral nutrition; Hands LJ et al.; The vitamin K requirements of 47 adult patients on total parenteral nutrition (TPN) were investigated by randomly allocating them to receive either 0.15 mg vitamin K1 (1 ampoule of 'Vitlipid') per week or 20.15 mg vitamin K1 (1 ampoule of 'Vitlipid' plus 10 mg vitamin K X 2) per week . Vitamin K1 in a dose of 0.15 mg was as effective as a dose of 20.15 mg per week in maintaining a normal BCR (British Corrected Ratio) in most TPN patients . Seven patients in each group developed a BCR greater than 1.3; this was significantly associated with the use of cephalosporin antibiotics and responded to 10 mg vitamin K1 per day . Most patients receiving parenteral feeding require no more vitamin K than that provided by 1 ampoule of 'Vitlipid' per week . Regular monitoring of the BCR, especially in patients on antibiotics, will reveal those who need more . Such patients need 10 mg vitamin K1 per day. Drug Intell Clin Pharm, 1985 Jul-Aug, 19(7-8), 553 - 5 Jaundice associated with cephalosporin therapy; Eggleston SM et al.; Two cases of cephalosporin-induced hepatotoxicity with associated jaundice are presented . Both patients developed jaundice and liver enzyme abnormalities soon after injectable cephalosporin therapy was started . Other possible causes were ruled out, including TPN and allopurinol hepatoxicity, and additional medical illnesses associated with hepatoxicity . Both patients recovered fully from the episode of jaundice . Review of the literature suggests a possible hypersensitivity reaction similar to liver toxicity of the penicillin antibiotics. Mikrobiologiia, 1985 Jul-Aug, 54(4), 523 - 8 {Differentiation of the fungus Acremonium chrysogenum and the synthesis of serine proteinases}; Bartoshevich IuE et al.; The biosynthesis of serine proteinases by the fungus Acremonium chrysogenum was studied in the process of its growth in media differing in the content of a protein substrate . Morphological differentiation of the submerged fungal culture was shown to be characterised by two reproduction pathways (conidiogenesis and arthrosporogenesis) and by the corresponding synthesis of serine proteinases II and I . The synthesis of serine proteinase I and cephalosporin was found to correlate with the polycyclic culture growth caused by the formation and germination of single spherical arthrospores. Zentralbl Bakteriol Mikrobiol Hyg {A}, 1985 Jul, 259(4), 531 - 7 The therapeutic response of cephalosporin-treated E . coli pyelonephritis of the rat, in relation to variations of the infection model; Schulz E et al.; In the E . coli pyelonephritis, induced in female Wistar rats by retrograde infection (high pressure reflux), we investigated the influence of 1) the time of commencement of therapy, 2) the renal bacterial counts, i.e . the inflammatory activity of the pyelonephritis after endovesical instillation of cultures with different bacterial concentrations, and 3) the level of infection resistance of the experimental animal strain on the therapeutic response of the model infection with single doses of cefoxitin (150 mg/ml) and cefotaxime (5 mg/ml) . Early commencement of therapy post inoculation was therapeutically advantageous provided the intrarenal multiplication of the infective organisms was not delayed or the initial bacterial concentrations were not too high . The mild form of pyelonephritis with lower renal bacterial concentrations and poor inflammatory activity after endovesical instillation of a low inoculum (10(4) cfu/ml) was less amenable to treatment than the inflammatory active pyelonephritis with high renal bacterial counts, using a high inoculum (10(7) cfu/ml) . High renal bacterial counts after retrograde inoculation of an E . coli culture of 10(8) cfu/ml resulted in significant reduction of bacterial counts 48, 72 and 96 h post infectionem, with i.m . application of cefoxitin 12 h prior . For Wistar rat strain Bor:WIST, which showed a stronger infection resistance with lower renal bacterial concentrations and a stronger tendency to spontaneous healing, application of a single dose of cefotaxime (5 mg/ml) was therapeutically ineffective, whereas, in contrast, with Han: WIST rats the acute phase of E . coli pyelonephritis could be treated effectively. Int J Clin Pharmacol Ther Toxicol, 1985 Jul, 23(7), 376 - 83 Clinical evaluation of ceftazidime in high risk patients; Montagnani M et al.; Ceftazidime was used in 19 patients at high risk owing to severe impairment of natural defense systems . The therapeutic efficacy and adverse reactions produced by cephalosporin, as evaluated on the basis of the results of clinical investigations and laboratory tests, were regarded as positive. Toxicology, 1985 Jun 28, 35(4), 295 - 305 Inhibition of cephaloridine-induced lipid peroxidation; Cojocel C et al.; The present study was designed to elucidate whether cephaloridine-induced lipid peroxidation is inhibited by probenecid, cobalt chloride and antioxidants such as alpha-tocopherol and N,N'-diphenyl-p-phenylenediamine (DPPD) . Kidney slices obtained from the renal cortex of male Wistar rats were incubated for 1 h in a cephaloridine or cefotaxime (1.25-10 mg/ml) containing medium . In another series of experiments, kidney slices were incubated with cephaloridine or cefotaxime (5 mg/ml) for different periods of time (30-120 min) . Lipid peroxidation was monitored by measuring the production of malondialdehyde (MDA) . Subsequently, kidney slices were incubated in both series of experiments, in a cephalosporin free medium containing tetraethylammonium (TEA) . Accumulation of TEA in renal cortical slices, expressed as slice to medium ratio (S/M), was used to measure changes in the transport capacity of the kidney cells . While cefotaxime had only a slight effect, cephaloridine induced a significant time- and concentration-dependent increase of MDA production and a significant time- and concentration-dependent decrease of TEA accumulation . Inhibition of the renal uptake of cephaloridine by probenecid induced a decrease in MDA production and complete recovery of TEA accumulation . The antioxidants DPPD and alpha-tocopherol inhibited cephaloridine-induced lipid peroxidation in a concentration-dependent manner . Recovery of TEA accumulation accompanied the decrease in lipid peroxidation . DPPD was a more potent inhibitor of lipid peroxidation than alpha-tocopherol . Cobalt chloride, known for its ability to decrease cellular concentration of cytochrome P-450, effectively decreased cephaloridine-induced lipid peroxidation . Thus, these findings support the concept that lipid peroxidation has an important role in the development of cephaloridine-induced nephrotoxicity. Antibiot Med Biotekhnol, 1985 Jun, 30(6), 410 - 4 {Effect of carbohydrate catabolic repression on the accumulation and intracellular distribution of methionine in Acremonium chrysogenum--the producer of cephalosporin C}; Bartoshevich IuE et al.; Dependence of the content of intracellular methionine and its distribution between the fraction of the high-molecular intracellular compounds and the cytoplasmic amino acid pool in the cephalosporin C-producing organism A . chrysogenum on the content of the carbohydrate source in the medium was studied . In the presence of both glucose and sucrose accumulation of methionine in the cells was observed prior to the antibiotic production . With the use of 35S- or 2(14)C-methionine it was shown that glucose had no repressing effect on methionine transport by the cells of different age (24 and 72 hours) . In the presence of glucose the higher levels of 35S- or 2(14)C-methionine were detected in the fraction of the low-molecular compounds of the cells within the first 36 hours of the culture growth . Apparently, the intracellular methionine was used to a larger extent for protein synthesis rather than for construction of the antibiotic molecule. J Biol Chem, 1985 May 25, 260(10), 6449 - 58 2.8-A Structure of penicillin-sensitive D-alanyl carboxypeptidase-transpeptidase from Streptomyces R61 and complexes with beta-lactams; Kelly JA et al.; The crystallographic structure of the penicillin-sensitive D-alanyl carboxypeptidase-transpeptidase from Streptomyces R61 has been solved to 2.8-A resolution . The 38,000-dalton serine peptidase has two regions of secondary structure, an alpha/beta cluster, and a region which contains five helical segments . The beta sheet is composed of five beta strands . The tertiary structure has no homology with the classic serine proteases or with the zinc carboxypeptidases . The binding at a common site of three types of beta-lactam (a penicillin, a cephalosporin, a monocyclic beta-lactam) and a desazacyclobutanone has been observed in Fourier difference maps . The binding site sequence is Val-Gly-Ser-Val-Thr-Lys . The beta-lactam ring lies near the enzyme's catalytic serine at position 37, and the C3 substituent of a cephalosporin falls near lysine 40. Can J Physiol Pharmacol, 1985 May, 63(5), 438 - 43 A comparative study of the inhibition of hepatic aldehyde dehydrogenases in the rat by methyltetrazolethiol, calcium carbimide, and disulfiram; Brien JF et al.; Methyltetrazolethiol (1-methyl-5-mercapto-1,2,3,4-tetrazole, MTT) is a heterocyclic substituent of the cephalosporin antibiotics, cefamandole, cefoperazone, and moxalactam . Pretreatment of rats with MTT has been reported to increase blood acetaldehyde concentration after ethanol administration . The time course of MTT-induced inhibition of hepatic aldehyde dehydrogenases (ALDH) was determined in adult, male Sprague-Dawley rats in comparison with the hepatic ALDH inhibition induced by calcium carbimide (calcium cyanamide, CC) and disulfiram (D) . The apparent onset of maximal inhibition of hepatic low Km ALDH occurred at 2 h for 50 mg/kg MTT (subcutaneous, s.c.) and 7 mg/kg CC (oral) and at 24 h for 300 mg/kg D (oral) . The relative magnitude of maximal inhibition of low Km ALDH was CC greater than D greater than MTT . The relative duration of enzyme inhibition was D greater than MTT greater than CC . High Km ALDH was only inhibited by CC . Hepatic low Km ALDH was selectively inhibited by s.c . and oral administration of 125 mg/kg MTT . For s.c . administration of 125 mg/kg MTT, the magnitude of maximal enzyme inhibition and the duration of inhibition were greater than for the 50 mg/kg dose . Oral administration of 125 mg/kg MTT produced similar inhibition of hepatic low Km ALDH compared with s.c . administration of the same dose . The time course of blood ethanol and acetaldehyde concentrations was determined for the intravenous infusion of two 0.3-g/kg doses of ethanol to rats that were pretreated orally with saline (1 h), MTT (125 mg/kg, 2 h), or CC (7 mg/kg, 1 h) . The relative increase in blood acetaldehyde concentration compared with saline pretreatment was CC greater than MTT . The elimination of ethanol from blood was slower in the MTT- and CC-pretreated animals, and this effect was more pronounced for CC pretreatment . Overall, the data demonstrate that the characteristics of hepatic ALDH inhibition for MTT are different from those of the known ALDH inhibitors, CC and D. Jpn J Antibiot, 1985 Apr, 38(4), 966 - 71 {Laboratory and clinical studies on cefpimizole in the field of gynecology}; Nakamura H et al.; Cefpimizole (AC-1370), a new cephalosporin antibiotic, was evaluated for its distribution in uterine tissue, penetration into retroperitoneal exudate and therapeutical effects on some infections in gynecology . The following results were obtained; The levels of AC-1370 in the cubital vein were similar to those in the uterine artery and this remained in the course of examinations after an 1 g intravenous injection . Seven patients with gynecological infections received AC-1370 by intravenous injection . The overall efficacy rate was 85.7% . No adverse reaction was observed in any of the cases treated with AC-1370, nor was there any marked changes in the laboratory findings. Jpn J Antibiot, 1985 Apr, 38(4), 921 - 5 {Application of cefpimizole in obstetrics and gynecology}; Usuki S et al.; We made fundamental and clinical studies of a new cephalosporin derivative, cefpimizole (AC-1370) . AC-1370 was relatively efficiently transferred into the uterine adnexa; in other words, it was as well transferred into the tissues as the other cephalosporin derivatives . There seemed to be no specific relation between its blood level and its level in any tissue . In 1 patient treated with AC-1370 for postoperative infection, clinical findings, WBC and CRP improved: the drug was evaluated as effective . Neither hepatic nor renal function was impaired in the patients treated with AC-1370 in the fundamental and clinical studies of the drug. Jpn J Antibiot, 1985 Apr, 38(4), 905 - 10 {Fundamental and clinical studies on cefpimizole in the field of obstetrics and gynecology}; Mure K et al.; Fundamental and clinical studies on cefpimizole (AC-1370), a new cephalosporin derivative, in the field of obstetrics and gynecology have been investigated, and the following results were obtained . High concentrations of AC-1370 in internal genital organs were detected after intravenous administration of 1.0 g of AC-1370 . In the treatment of 14 cases of infection, the therapeutic effects were excellent or good in 11 cases and overall efficiency rate excluding 1 case with side effects was 84.6% (11/13) . No serious side effect was observed except 1 case of nausea and vomiting. Pediatr Med Chir, 1985 Mar-Apr, 7(2), 239 - 42 {Multicenter trials of a new cephalosporin (ceftriaxone) in childhood}; De Francesco F et al.; AA . have tested a new drug (Ceftriaxone) on 40 children affected by upper and lower respiratory tract infectious diseases . As shown by results, this new drug has been remarkably effective and easy to use since it may be administered once in a day; moreover, the tested drug has not caused any kind of tissue or parenchymal involvement. Rev Med Interne, 1985 Mar, 6(2), 163 - 77 {Pharmacokinetics and tissue penetration of ceftriaxone}; Bergan T; This article describes the pharmacokinetics of ceftriaxone, a new "third generation" cephalosporin . This antibiotic displays two major characteristics: a very long serum half-life and a good tissue penetration . The properties of ceftriaxone should allow its easy clinical handling. J Antibiot (Tokyo), 1985 Mar, 38(3), 380 - 9 KY-109, a new bifunctional pro-drug of a cephalosporin . Chemistry, physico-chemical and biological properties; Kakeya N et al.; (5-Methyl-2-oxo-1,3-dioxol-4-yl)methyl 7-{D-O-(L-alanyl)mandelamido}-3-{{(5-methyl-1,3, 4-thiadiazol-2-yl)thio}methyl}-3-cephem-4-carboxylate hydrochloride (KY-109) was synthesized as a bifunctional pro-drug designed to improve the oral absorption of the parent drug (KY-087), a cephalosporin similar in activity to cefamandole . The pro-drug was found to possess the desired factors for an orally active pro-drug, that is, appropriate solubility, lipophilicity and ease hydrolysis into the parent drug . As predicted from these factors, the pro-drug when administered orally to rats was well absorbed, and gave high blood levels of the parent drug. Res Commun Chem Pathol Pharmacol, 1985 Mar, 47(3), 357 - 71 Effect of cephalosporins on organic ion transport in renal membrane vesicles from rat and rabbit kidney cortex; Williams PD et al.; The effects of cephaloridine and cephalothin on prototypical organic anion (p-aminohippurate, PAH) and cation (N-methylnicotinamide, NMN) transport were observed in brush border and basolateral membrane vesicles prepared from rat and rabbit renal cortex . The cephalosporins interacted with both the cationic and anionic transport systems . Cephalothin inhibited PAH transport in basolateral and brush border membrane in both rats and rabbits . Cephaloridine on the other hand inhibited PAH and NMN transport across rabbit basolateral membranes while it showed a lack of interaction with transport systems in rat basolateral membranes . Conversely, cephaloridine inhibited brush border transport of PAH and NMN in the rat but not in the rabbit . These results provide indirect evidence that cephalothin may be secreted across the renal tubule cell in rats and rabbits while cephaloridine may not accumulate in the rat kidney and becomes trapped in rabbit renal tubule cells . The differences in transport effects observed may explain intra- and interspecies differences in susceptibility to cephalosporin nephrotoxicity. FEBS Lett, 1985 Feb 11, 181(1), 143 - 8 Difference in pathway of Escherichia coli outer membrane permeation between penicillins and cephalosporins; Yamaguchi A et al.; The differences in the outer membrane permeation between two major subgroups of beta-lactam antibiotics were studied . The permeation of cephalosporins was closely related to porin channels in the outer membrane . In contrast, the outer membrane permeation of penicillins did not decrease in porin-deficient mutants and, in Rd-type mutants, their permeability became proportional to the hydrophobicity of the molecules . The activation enthalpy of the penicillin permeation was significantly larger than that of cephalosporins . These observations indicate that penicillins can use the hydrophobic region for the major route of outer membrane passage whereas the cephalosporin permeation is restricted to the pathway via the porin pore. Jpn J Antibiot, 1985 Jan, 38(1), 13 - 7 {Clinical studies on ceftriaxone in the field of obstetrics and gynecology}; Murakami M et al.; Clinical studies were made on ceftriaxone (CTRX, Ro 13-9904), a new long-acting cephalosporin antibiotic, with the following results . Following a single intravenous injection of 1 g, the transfer of CTRX to the internal genital organs was found to be good . The transfer of CTRX to exudate of the dead space of pelvis was also good . Elbow vein and uterine artery blood serum levels revealed marked increase immediately after administration, then followed by gradual reduction at very slow rate . CTRX was given to 3 patients of female genital infections . Efficacy was excellent in 1 case and good in 2 cases . As to side effect, 2 cases of diarrhea and 1 case of leukopenia were observed. Arch Microbiol, 1985 Jan, 140(4), 317 - 20 Repression and inhibition of cephalosporin synthetases in Streptomyces clavuligerus by inorganic phosphate; Lubbe C et al.; Cephalosporin production by growing cells of Streptomyces clavuligerus was reduced by 100 mM inorganic phosphate . Resting cell production was repressed by prior growth in high phosphate and inhibited by phosphate . The cell-free activity of desacetoxycephalosporin C synthetase (ring expansion activity) was repressed by prior growth in high phosphate and inhibited by phosphate . Isopenicillin N synthetase (cyclase) was inhibited but not repressed . Penicillin epimerase was neither inhibited nor repressed by phosphate. J Clin Microbiol, 1985 Jan, 21(1), 133 - 4 Effect of refrigerated storage on cefaclor in Mueller-Hinton agar; Surprenant AM et al.; Cefaclor is less stable than most cephalosporins in media at 35 degrees C . We demonstrated that the activity of cefaclor in Mueller-Hinton agar diminishes continuously at 4 degrees C, resulting in a loss of two-thirds of the activity within 21 days . We recommend that agar dilution plates for this cephalosporin be prepared on the day of their use. Drugs Exp Clin Res, 1985, 11(7), 441 - 5 Cefatrizine: a clinical overview; Santella PJ et al.; Cefatrizine, a new oral cephalosporin, proved effective in the treatment of a wide range of bacterial infections in both adult and paediatric patients . Adverse reactions mild and mainly limited to gastrointestinal disturbances. Drugs Exp Clin Res, 1985, 11(2), 83 - 8 The influence of some cephalosporins on immunological response; Borowski J et al.; The effect of cefotaxime and cephradine on the activity of some immune mechanisms was investigated in mice . It was found that cefotaxime in therapeutic doses did not affect the humoral and cellular immune response against sheep erythrocytes, whereas cephradine suppressed the humoral response in doses corresponding to those used for the treatment of patients . The response in vitro of mouse spleen lymphocytes to PHA was suppressed by both cephalosporins; however this occurred at therapeutic concentrations only in the case of cephradine . Neither cephalosporin affected the phagocytic and chemotactic activity of mouse peritoneal macrophages and rabbit microphages. Br J Haematol, 1985 Jan, 59(1), 9 - 14 Cephalosporin-induced immune neutropenia; Murphy MF et al.; Neutropenia is an occasional complication of treatment with cephalosporin antibiotics . This report describes two patients who had neutropenia while receiving high doses of cephalosporins . The neutrophil counts returned to normal after stopping the drug, and cephalosporin-dependent neutrophil antibodies were demonstrated in both cases, using the granulocyte immunofluorescence test . In one patient, the immune neutropenia appeared to be due to a drug adsorption mechanism similar to penicillin-induced haemolytic anaemia, while an immune complex mechanism may have been involved in the second patient. Drugs Exp Clin Res, 1985, 11(7), 453 - 6 Determination of cefatrizine levels in blood, tonsils, paranasal sinuses and middle ear; Santacroce F et al.; Levels of cefatrizine, a new oral cephalosporin, were determined in blood and in tonsils, paranasal sinus secretions and middle ear exudates from 18 patients with acute infections at these sites . Three and six hours after administration of 500 mg cefatrizine satisfactory levels of the antibiotic were found at all the sites examined . Levels in the tonsils and middle ear were higher than those in blood, while lower levels were recorded in nasal secretions. JAMA, 1984 Dec 21, 252(23), 3277 - 9 Prophylactic parenteral cephalosporins in surgery . Are the newer agents better? DiPiro JT, Bowden TA Jr, Hooks VH 3rd. Parenteral prophylactic cephalosporins used in surgery were compared in 17 published studies . Examination of these studies reveals little justification for preference of one cephalosporin over another . For gastrointestinal, obstetrical-gynecologic, or cardiac operations, newer cephalosporins did not result in substantial decreases in adverse postoperative clinical events (eg, wound infections, intra-abdominal and pelvic infections, and endocarditis) when compared with older cephalosporins . There is no evidence that second- or third-generation cephalosporins result in postoperative infection rates lower than with first-generation cephalosporins. Appl Environ Microbiol, 1984 Dec, 48(6), 1084 - 7 Changes in the lipid composition of Paecilomyces persicinus P-10 M1 during growth and cephalosporin C production; Papacharilaou E et al.; The lipid composition of the fungus Paecilomyces persicinus P-10 M1 was monitored daily for 6 days to detect any changes during growth and cephalosporin C production . Total lipid yields and cephalosporin C production were maximal after 72 h of incubation . Analysis of the total lipids revealed that the neutral lipid fraction was elevated at this time, whereas polar lipids were depressed . Phosphatidylethanolamine and phosphatidylcholine represented the major phospholipids detected . Phosphatidylethanolamine levels were descending when cephalosporin C was detected at its highest concentration . Increases in phosphatidylcholine levels paralleled those of cephalosporin C but reached a maximum at 48 h after the latter . Diphosphatidylglycerol, phosphatidic acid, and phosphatidylserine were also detected . Fatty acids present in the total lipid fraction ranged in carbon length from C12 to C24 . The major acids were C16 (palmitic), C18:1 (oleic), and C18:2 (linoleic) . All fatty acids exhibited minor variations in concentration during the 6-day period, and none displayed a direct correlation with cephalosporin C yields. Chemioterapia, 1984 Dec, 3(6), 390 - 3 Cross allergenicity between penicillins and cephalosporins; Beam TR Jr et al.; Twenty patients excluded from pre-marketing trials of cephalosporin antibiotics as chemoprophylaxis for open heart surgery were enrolled in an evaluation of skin-test reactivity . All gave a history of type I hypersensitivity to penicillins . None knew of adverse reactions to cephalosporins . Eighteen were negative to testing with saline, cefazolin, ceftriaxone, penicillin G and benzyl-penicilloyl . Two patients with positive skin tests safely received vancomycin chemoprophylaxis . We conclude that most patients who give a positive allergic history but have negative skin tests can safely receive cephalosporin chemoprophylaxis. Am J Hosp Pharm, 1984 Dec, 41(12), 2624 - 34 Variable cost per dose of preparing and administering small-volume cephalosporin admixtures . Veterans Administration Pharmacy Service Study Group; Susceptibility of Eikenella corrodens to penicillin et al.; The susceptibility of 29 strains of Eikenella corrodens to penicillin, apalcillin, and 12 new cephalosporins was determined by the agar dilution method . Most strains were resistant to cefsulodin, and some were resistant to apalcillin and cefpiramide . Although all strains were susceptible to the other cephalosporins tested, most of those drugs were as active as or less active than penicillin . Susceptibility testing of isolates should be performed whenever a cephalosporin is used to treat infections involving E . corrodens. J Med Chem, 1984 Dec, 27(12), 1657 - 63 3-Substituent effect and 3-methylene substituent effect on the structure-reactivity relationship of 7 beta-(acylamino)-3-cephem-4-carboxylic acid derivatives studied by carbon-13 and IR spectroscopies; Nishikawa J et al.; Relationships between the chemical reactivity of 3-substituted cephalosporins or 3-methylene-substituted cephalosporins and several parameters observed by 13C NMR and IR spectroscopies are described . Among 3-substituted cephalosporins, the values of delta (C-3) and delta (COO) of 13C NMR spectra are correlated with the logarithms of the rate constants for alkaline hydrolysis (log kobsd) when substituents at the 3-position are classified into two groups, i.e., OR substituents and others . Among the 3-methylene-substituted cephalosporins, the difference values of the 13C chemical shifts for C-3 and C-4, delta delta (4-3), are correlated with log kobsd . The beta-lactam vC = O value of the solution IR spectra is a good index for the prediction of a significant change of the beta-lactam reactivity resulting from modification of a 3-substituent or a 3-methylene substituent . From analysis of these observed parameters, both resonance and inductive effects of the substituent at the 3-position were found to affect the chemical reactivity of the beta-lactam ring in cephalosporin, while only the inductive effect of the substituent at the 3'-position was found to affect the beta-lactam reactivity. Jpn J Antibiot, 1984 Dec, 37(12), 2416 - 9 {Fundamental study on tissue distribution of ceftriaxone in the field of obstetrics and gynecology}; Fukuda O et al.; Fundamental study on tissue distribution of ceftriaxone (Ro 13-9904, CTRX), a new cephalosporin parenteral antibiotic, was studied and the following results were obtained . CTRX had been administered by intravenous drip infusion with 1 g to 9 cases who received simple total hysterectomy . The level of CTRX in the cubital venous serum and uterine arterial serum was determined as well as the tissue concentration in the oviduct, ovary, endometrium, myometrium, cervix uteri and portio vaginalis . The level in the oviduct and portio vaginalis was generally high, although it was observed only in a few cases . The variation of the level in the myometrium was large . CTRX is expected to be clinically useful considering the fact that its half-life time is 8.5 hours, which is longer than that of existing cephalosporin antibiotics. Jpn J Antibiot, 1984 Dec, 37(12), 2397 - 405 {Fundamental and clinical evaluation of ceftriaxone in the field of obstetrics and gynecology}; Haramaki Y et al.; Fundamental and clinical evaluation on ceftriaxone (Ro 13-9904, CTRX), a new cephalosporin antibiotic, was performed in the field of obstetrics and gynecology and the following results were obtained . The concentration of CTRX after intravenous injection was determined in the arterial and venous blood, and in the internal genital organs and a favorable tissue transfer was observed . The clinical efficacy rate was not very high (40%); good in 2 out of 5 cases with gyneco-obstetric infections, but it is notable that efficacy was recognized in the case which B . fragilis was detected . Neither adverse reaction nor laboratory test abnormality was seen to be attributable to CTRX in any case. Jpn J Antibiot, 1984 Dec, 37(12), 2391 - 6 {Study on transfer of ceftriaxone into female genital organs}; Hongo M et al.; One gram of ceftriaxone (Ro 13-9904, CTRX), a new cephalosporin antibiotic, was given intravenously to a total of 25 patients prior to abdominal total hysterectomy for uterine myoma with or without small benign ovarian tumor . Bilateral uterine arteries were clamped at 0.5, 1, 2, 6, 12 and 24 hours after administration, and serum samples and uterine tissues were taken for the measurement of CTRX concentration by bioassay method . A little difference was found in the serum concentration between cubital venous and uterine arterial serum, the half-lives being 8.0 and 7.9 hours, respectively . The initial concentrations were estimated to be 153 micrograms/ml and 160 micrograms/ml, respectively . The tissue peak concentrations were obtained at 30 minutes in the myometrium, portio vaginalis, oviduct and ovary, and at 1 hour in the endometrium and cervix uteri . These were 41, 51, 51, 39, 42 and 47 micrograms/g, respectively . The tissue concentrations after peak decreased in the same manner as the serum concentrations . Judging from its favorable transfer into the uterine tissues, CTRX was evaluated to be clinically useful in the treatment of obstetrical and gynecological infections. Jpn J Antibiot, 1984 Dec, 37(12), 2384 - 90 {Fundamental and clinical study of ceftriaxone in the field of obstetrics and gynecology}; Hirabayashi K et al.; Ceftriaxone (Ro13-9904, CTRX), a newly developed cephalosporin antibiotic, was fundamentally evaluated through determination of the levels in the female genital organ tissues and in the pelvic dead space exudate . CTRX was also studied on its clinical efficacy in 13 cases with gyneco-obstetric infections . The transmission of CTRX into the female genital organ tissues was favorable: the peak level in each tissue was as high as 38 to 63 micrograms/g 18 to 37 minutes after administration . The level in each tissue even after about 18 hours remained around 10 micrograms/g, suggesting its better transmission into the tissues than other drugs . The transmission into the pelvic dead space exudate was also good: the level reached a peak of 100 to 120 micrograms/ml 1 to 3 hours after administration and still ranged from 74 to 76 micrograms/ml even after about 12 hours . The clinical efficacy was excellent in 5, good in 5 and poor in 3 out of 13 cases with gyneco-obstetric infections and the efficacy rate was 76.9% . Neither adverse reaction nor laboratory test abnormality was observed in any case . The above-mentioned results suggest that CTRX is a useful antibiotic for gyneco-obstetric infections. Jpn J Antibiot, 1984 Dec, 37(12), 2377 - 83 {Basic and clinical studies of ceftriaxone in the field of obstetrics and gynecology}; Doko F; Ceftriaxone (Ro 13-9904, CTRX), a new cephalosporin antibiotic, was basically and clinically studied in the field of obstetrics and gynecology . The following results were obtained . The pelvic dead space exudate and serum levels of CTRX were measured in patients with radical hysterectomy with pelvic lymphadenectomy for uterine cervical cancer after the intravenous injection of 1 g . Immediately after the injection, the serum level increased to 146 micrograms/ml on average and thereafter declined rapidly . The pelvic dead space exudate level attained the peak of 88 micrograms/ml after 4 hours and thereafter declined gradually but was 74 micrograms/ml even at 8 hours after the injection . A total of 13 cases comprising 2 with intrauterine infection, 5 with pelveoperitonitis, 4 with adnexitis and 2 with external genital organ infection were intravenously treated with CTRX at a dose of 1 g twice daily for 3-7 days . The clinical results were good in 12 cases and unknown in 1 case . Eruption was noted in 1 case. Jpn J Antibiot, 1984 Dec, 37(12), 2355 - 63 {Fundamental and clinical studies on ceftriaxone in the field of obstetrics and gynecology}; Yamamoto T et al.; Fundamental and clinical studies on ceftriaxone (CTRX, Ro 13-9904), a new cephalosporin antibiotic, were carried out with the following results . Concentration of CTRX was examined in serum, internal genital organs and retroperitoneal fluid after single intravenous administration of 1.0 g dose . The venous serum level of CTRX was 156 micrograms/ml at 5 minutes after the administration . The favorable transfer of CTRX to internal genital organs and retroperitoneal fluid was demonstrated . In clinical trial, CTRX was given to 10 cases with obstetrical and gynecological infections such as endometritis, adnexitis, pelvic peritonitis and parametritis . The efficacy was evaluated as excellent in 1 case, good in 8 cases and poor in 1 case . No side effects were observed in any of the cases treated with CTRX. Jpn J Antibiot, 1984 Dec, 37(12), 2298 - 303 {Experimental and clinical evaluation on ceftriaxone in the field of obstetrics and gynecology}; Satoh T et al.; Ceftriaxone (CTRX), a new cephalosporin antibiotic, was evaluated in the field of obstetrics and gynecology and the following results were obtained . The concentration of CTRX after an intravenous injection with 1 g was determined in the uterine artery, cubital vein and in the intrapelvic genital tissues such as the oviduct, ovary, endometrium, myometrium, cervix uteri and portio vaginalis . The peak level was 160 micrograms/ml at 26 minutes after injection both in the uterine arterial serum and cubital venous serum, 48 and 38 micrograms/g at 1 hour and 18 minutes in the tissues of oviduct and ovary, respectively, 54 and 50 micrograms/g at 48 minutes in the myometrium and cervix uteri, respectively, while 46 micrograms/g at 39 minutes in the portio vaginalis . The mean level 18 to 24 hours after administration was 19 micrograms/ml in the uterine arterial serum and cubital venous serum and 6.3 micrograms/g in the intrapelvic genital tissues . A case of intrapelvic infection clinically showed an excellent response without any side effects by intravenous drip infusion with 2 g divided as twice a day for 7 days . The above results show that CTRX is useful in the field of obstetrics . and gynecology. Antimicrob Agents Chemother, 1984 Nov, 26(5), 752 - 6 Differential stimulation of lymphocyte cell growth in vitro by cephalosporins; Leyhausen G et al.; The in vitro effect of three cephalosporins (cefodizime, cefotaxime, and ceftizoxime) on the growth of the following lymphocytes or their derivatives was tested: L 5178y mouse lymphoma cells, Molt-4 cells, and murine splenic lymphocytes . Within the concentration range of 0.1 to 50 microM, the cephalosporins had no effect on L 5178y cell growth . However, Molt-4 cell growth was significantly stimulated by 0.3 to 20 microM cefotaxime and cefodizime but was not influenced by ceftizoxime . Binding studies with {14C}cefotaxime revealed that the Molt-4 cells responding to the drug bind this cephalosporin to their cell surface (1.9 X 10(5) molecules per cell); no significant binding was observed in the assays with L 5178y cells . Determinations of the extractable activities of DNA-synthesizing enzymes from cefodizime-treated Molt-4 cells showed a direct correlation between cell growth and DNA polymerase alpha as well as terminal deoxynucleotidyl transferase activity; the DNA polymerase beta activity remained unchanged . Cefodizime (0.15 to 50 microM) which was added to mouse spleen cell cultures significantly increased {3H}thymidine incorporation into lymphocytes . This stimulatory effect was less pronounced in concanavalin A-stimulated cultures . These findings suggest that some cephalosporins display a growth-stimulating influence on some lymphocyte populations. Antimicrob Agents Chemother, 1984 Nov, 26(5), 652 - 5 High-pressure liquid chromatographic method for analysis of cephalosporins; Signs SA et al.; A high-pressure liquid chromatographic method is described for the analysis of a wide range of cephalosporin congeners, using only three reagents for extraction and drug analysis . Plasma was treated with cold methanol-0.1 M sodium acetate to precipitate protein . Cephalosporins were resolved on a C-18 reverse-phase column, utilizing a mobile phase of various percentages of 0.01 M sodium acetate and acetonitrile-methanol . Compounds analyzed included cephalexin, cefamandole, cephalothin, cefotaxime, cefazolin, cephaloridine, cefoxitin, cefaclor, cephapirin, and cefoperazone . Each antibiotic demonstrated excellent linearity throughout the therapeutic range . The method of standard additions revealed recoveries of 93 to 101%, with detection limits ranging from 0.2 to 1.0 micrograms/ml for these drugs . Retention times ranged from 4 to 6 min . This method offers a rapid and simple means by which this group of cephalosporins may be reliably quantitated. Clin Pharm, 1984 Nov-Dec, 3(6), 626 - 9 Efficacy of 0.9% sodium chloride injection with and without heparin for maintaining indwelling intermittent injection sites; Epperson EL; The efficacy of 0.9% sodium chloride injection with and without heparin in maintaining indwelling intermittent ("heparin lock") injection sites was studied . All patients in whom heparin locks were placed after admission to the medical and surgical units of a 128-bed acute-care hospital during a six-month period were included in the study . Three different solutions were used to flush heparin locks: 0.9% sodium chloride injection alone, heparin 10 units/ml in 0.9% sodium chloride injection, and heparin 100 units/ml in 0.9% sodium chloride injection . Solutions were randomly assigned to all patients on a given nursing unit for a two-month period; flush solutions were switched every two months until each of the three solutions had been used on both the medical and surgical units . Heparin locks were flushed after each medication administration and every eight hours when medications were not being given . Using a standardized evaluation form, one of five i.v . therapists evaluated each site daily for the presence of phlebitis and loss of patency . Length of catheter placement and the percentage of patient days during which patients received cephalosporin and penicillin antibiotics were examined for each group . Rates of site loss caused by phlebitis or loss of patency were compared in each group . A total of 412 patients representing 1448 patient days of heparin-lock therapy was evaluated . No significant differences were found among the three groups in the mean duration of heparin-lock placement, the percentage of patient days during which antibiotics were prescribed, or the rate of site loss caused by phlebitis or loss of patency.(ABSTRACT TRUNCATED AT 250 WORDS) Am J Hosp Pharm, 1984 Nov, 41(11), 2359 - 62 Cephalosporin-use restrictions in teaching hospitals; McCloskey WW et al.; A survey of pharmacy directors in teaching hospitals was conducted in March 1983 to ascertain policies for management of cephalosporin use . Surveys were sent to 298 institutions in each of the United States except Alaska . Respondents were asked various questions regarding hospital policies on cephalosporin use . Responses were received from 179 hospitals that had formularies; 99 of these had formal restriction policies, more frequently for second- and third-generation agents than for first-generation agents, and 13 planned to institute restriction policies . In 68% of hospitals with restriction policies, restricted drugs were released only after consultation with the infectious disease service . Chart review was the most frequently reported method of monitoring use of restricted cephalosporins . Approximately 40% of respondents had therapeutic equivalence policies, and more than 40% had recently deleted one or more cephalosporins from the formulary . The percentage of hospitals with formal restriction policies (55%) was greater than in a 1979 survey (32%) . Many teaching hospitals have initiated policies to curb rising drug costs associated with the use of cephalosporin antibiotics. Toxicol Lett, 1984 Nov, 23(2), 135 - 40 Acute and subacute toxicity studies of AC-1370 sodium in mice and rats; Hashimoto S et al.; The i.v . LD50 of the cephalosporin antibiotic 7-beta-D(-)-alpha-{4(5)-carboxyimidazole-5(4) carboxamido}phenylacetamido-3-(4-beta-sulfoethylpyridinium) methyl-3-cephem-4 carboxylic acid sodium (AC-1370 sodium) for the rat was found to be 4.2 and 3.5 g/kg body weight for males and females, respectively; corresponding values for the mouse were 2.7 (male) and 2.9 (female) . Daily i.v . administration to rats for 35 days caused decreased food intake and increased water consumption and body weight gain, relative increase of kidney weight, elevated blood urea nitrogen (BUN) and proteinuria, renal tubular degeneration and/or necrosis and ballooning of the caecum at 1500 mg/kg/day, and less marked changes at 500 mg/kg/day . There were so significant adverse effects at 40 or 150 mg/kg/day . The approximate LD50 values (g/kg) by other routes were: s.c . mouse, 7-8; s.c . rat, 11-12; i.m . mouse and rat, greater than 1.2; per os mouse and rat, greater than 15. Can J Surg, 1984 Nov, 27(6), 616 - 8 Human bite injuries of the hand; Bite U; The charts of 24 patients admitted to Victoria Hospital, London, Ontario with human bite injuries were analysed . Two clinical groups were found . One group of patients had evidence of septic arthritis . They required operative treatment and experienced complications . The second group was made up of patients with cellulitis who responded to antibiotic therapy and had an uncomplicated course . No resistance to cephalosporins was found . Patients seen soon after injury without evidence of joint penetration should be managed by irrigation and open management of the wound, immobilization in a hand dressing, elevation, tetanus prophylaxis, oral administration of a cephalosporin and reexamination within 24 hours . Those who fail to respond to this treatment should be admitted to hospital and given antibiotics intravenously . Clinical evidence of septic arthritis warrants early operative incision and drainage combined with antibiotics given intravenously. Rev Infect Dis, 1984 Nov-Dec, 6 Suppl 4, S909 - 23 Economic analysis of a new drug: potential savings in hospital operating costs from the use of a once-daily regimen of a parenteral cephalosporin; Eisenberg JM et al.; The introduction of a new drug requires clear demonstration of its clinical efficacy and documentation of its adverse effects, but economic consequences of the new drug generally receive less attention . A new cephalosporin antibiotic, cefonicid, can be administered parenterally once daily, rather than three or four times daily, which is required for conventional cephalosporins . Methods of industrial engineering and cost accounting were used to determine the potential savings in hospital operating costs that would be available by reducing the frequency of intravenous administration of cephalosporin antibiotics . The variable cost of administering parenteral cephalosporin antibiotics averaged $2.24 per dose, $0.95 of which was attributable to labor costs and $1.28 to the costs of materials . Given present patterns of cephalosporin use, at four study hospitals the average potential savings per day for patients receiving intravenous cephalosporins ranged from $3.72 to $7.23, with a weighted mean of $5.42 . Estimated national savings in hospital operating costs that would occur with use of an intravenous cephalosporin administered once daily range from $85.1 million to $115.4 million yearly. Rev Infect Dis, 1984 Nov-Dec, 6 Suppl 4, S905 - 8 New drugs and clinical economics: analysis of cost effectiveness in the assessment of pharmaceutical innovations; Eisenberg JM; New drugs undergo rigorous clinical testing to determine their efficacy and adverse effects . However, seldom is the potential financial impact of a new drug carefully assessed before its introduction . Cost-benefit and cost-effectiveness analyses provide methods of determining the effect of drugs and other services on costs of medical care . Methods of industrial engineering and cost accounting can be used to determine the additional cost of medical care associated with the drug; such cost finding provides more accurate economic data than does the use of hospital charges . This symposium includes two clinical economic studies of the potential effect of introducing a cephalosporin antibiotic that requires administration only once daily . Both studies estimate substantial savings in direct hospital expenditures. Hinyokika Kiyo, 1984 Nov, 30(11), 1711 - 35 {Clinical results and safety of ceftazidime, a new injectable cephalosporin, in long-term administration of the treatment of infections in urology}; Suzuki K et al.; CAZ was administered to 34 patients in the field of urology for treatment or prevention of serious infections with many complicated factors . The duration of treatment ranged from 9 to 30 days, the most frequent being 14 days, which was the duration originally set as the standard . As the results CAZ was considered to be one of the drugs of choice in the cases requiring long-term treatment, from the viewpoint of both efficacy and usefulness. Rev Infect Dis, 1984 Nov-Dec, 6 Suppl 4, S901 - 4 A double-blind study comparing cefonicid with cefazolin as prophylaxis in patients undergoing total hip or knee replacement; DeBenedictis KJ et al.; In a randomized double-blind design, cefonicid, an investigational cephalosporin, was compared with cefazolin as prophylaxis in 76 patients undergoing total hip or knee replacement . Risk factors were similar in both groups, and no toxicity was seen with either the control drug, cefazolin, or the test drug, cefonicid . In this small group of patients followed for a short period (four months to one year), no wound sepsis or early or delayed prosthetic sepsis was found, and no superiority of one drug over the other could be demonstrated . Because of the already low incidence of prosthetic infection in patients given appropriate prophylaxis, a larger sample size and a more extended follow-up would be necessary to show increased efficacy of a new compound relative to that of an accepted and proven older drug. J Antibiot (Tokyo), 1984 Nov, 37(11), 1441 - 8 In vitro biological activities of 6-isosteric penicillins and 7-isosteric cephalosporins; Sheehan JC et al.; Antibiotic and penicillinase inhibitor activities of various penicillin and cephalosporin analogs are reported . The compounds include C-6 penicillin and C-7 cephalosporin carbon, oxygen and sulfur analogs obtained by replacing the NH of the amide side chains with CH2, O and S, respectively . In almost all cases, analogs were considerably less active than the standard compounds (benzylpenicillin and cephalothin) . However, some of the analogs act as penicillinase inhibitors. Am J Surg, 1984 Oct 19, 148(4A), 1 - 4 Combined ceftriaxone and surgical therapy for osteomyelitis in hospital and outpatient settings; Eron LJ et al.; The combined medical-surgical approach to therapy for osteomyelitis requires patients to receive intravenous antibiotics three to six times daily for 4 to 6 weeks after initial surgical debridement . The greatly extended half-life of the new cephalosporin, ceftriaxone (6 to 8 hours), enabled its intravenous administration once or twice daily to 76 patients for the treatment of osteomyelitis . Cure or improvement was noted in 66 of the 76 patients (87 percent) . Most of the failures occurred in the group of patients with osteomyelitis complicated by vascular insufficiency . The once or twice daily dosing possible with ceftriaxone was particularly advantageous for permitting highly cost-effective at home therapy for 42 of the 76 patients. Antimicrob Agents Chemother, 1984 Oct, 26(4), 604 - 5 Susceptibility of Bordetella pertussis to cephalosporin derivatives and imipenem; Bannatyne RM et al.; The in vitro activities of 16 cephalosporin derivatives and imipenem against 60 strains of Bordetella pertussis were examined . Cefoperazone, imipenem, and ceftriaxone were the most active, with MICs that inhibited 90% of the strains of 0.006, 0.05, and 0.1 microgram/ml, respectively . Cephalexin, cephradine, and cefsulodin were the least active, with MICs of 25 to 125 micrograms/ml . The remainder of the agents demonstrated intermediate activity. Biochem J, 1984 Sep 15, 222(3), 777 - 88 Stereochemistry of the incorporation of valine methyl groups into methylene groups in cephalosporin C; Pang CP et al.; 'Chiral methyl valines', i.e . samples of valine labelled stereospecifically in the methyl groups with 2H and 3H, were incorporated into cephalosporin C by a suspension of washed cells of Cephalosporium acremonium . Analysis by 3H n.m.r . of the cephalosporin C produced showed that the conversion of the 3-pro-S-methyl group of valine into the acetoxymethyl side-chain was a highly stereospecific process . By contrast, conversion of the 3-pro-R-methyl group into the endocyclic methylene group of the dihydrothiazine ring was shown to proceed by a non-stereospecific process. Antimicrob Agents Chemother, 1984 Sep, 26(3), 373 - 7 Renal disposition of ceftazidime illustrated by interferences by probenecid, furosemide, and indomethacin in rabbits; Carbon C et al.; Excretion of ceftazidime (C), a new cephalosporin antibiotic, has been reported to occur unexpectedly through glomerular filtration only, without being significantly affected by probenecid . We investigated renal tubular disposition of C in rabbits by calculating its rates of fractional excretion, net tubular secretion, and absolute excretion . During continuous intravenous infusion of C, 3 mg of furosemide (F), 15 mg of probenecid (P), or 2 mg of indomethacin (I) per kg was injected intravenously as a bolus . Equilibrium dialysis showed that the percentage of C bound to serum proteins (14 +/- 5%) was not altered by F, P, or I . Fractional excretion of C was 94 +/- 22, 65 +/- 21, 182 +/- 36, and 98 +/- 3% for the drug given alone and after injection of F, P, and I, respectively . For 15 min after P injection, we observed net tubular secretion of C (404 +/- 276 micrograms/min) . The C absolute excretion rate was significantly reduced by I compared with the absolute excretion rate for the control (405 +/- 104 versus 696 +/- 157 micrograms/min) . We conclude that (i) C undergoes bidirectional transport in the nephron, revealed by the effects of F and P, with a nil net C balance; (ii) F and P have opposite unexpected effects on tubular handling of C, possibly due to competition for C secretion processes; (iii) I reduces C excretion solely by decreasing its glomerular-filtered load; and (iv) tubular handling of C differs from that of previously studied cephalosporins. Rev Infect Dis, 1984 Sep-Oct, 6(5), 732 - 5 Is renal function the only determinant in the elimination of ceftazidime? Narang PK, Hunter JR. Ceftazidime is a third-generation cephalosporin that is eliminated primarily via the kidneys . Several studies have indicated that dosage adjustment is necessary in patients with renal disease . The correlation between the glomerular filtration rate and half-life (t 1/2) developed by Norrby and co-workers was used to evaluate, in three patients, the hypothesis that renal function is the principal determinant in excretion of the ceftazidime . Results obtained indicate that although the correlation appeared valid for a patient with chronic renal failure it did not predict patterns of ceftazidime elimination in two granulocytopenic patients with lymphoma . Therefore, caution should be exercised when employing Norrby's correlation for adjusting ceftazidime dosage for patients with certain disease states. Antimicrob Agents Chemother, 1984 Sep, 26(3), 368 - 72 Pharmacokinetics of cefotiam and cefsulodin after simultaneous administration to patients with impaired renal function; Lecaillon JB et al.; The possible influence of the concomitant administration of cefotiam and cefsulodin on their respective pharmacokinetics was studied in 15 patients with renal insufficiency and 10 anuric patients . Linear relations were found between the clearance of creatinine and the total clearance, as well as the renal clearance, of each drug . These relations for each cephalosporin were not significantly different from previous results obtained after separate administration . In hemodialyzed patients, the two cephalosporins were readily eliminated from the blood after simultaneous administration: ca . 35% of the dose of cefotiam and 30% of the dose of cefsulodin was recovered in the dialysate over 5 h . These results suggest that the pharmacokinetics of the two drugs are not modified by their simultaneous administration and that the dosing schedule previously proposed for administration of the two cephalosporins alone in the presence of renal insufficiency can be applied without modification when they are given together . Patients on hemodialysis should receive a loading dose after each dialysis period, and then reduced doses according to recommendations for anuric patients. J Pharmacobiodyn, 1984 Aug, 7(8), 586 - 92 Epileptogenic activity induced by intravenous injection of certain cephalosporins in rats; Yu QH et al.; Epileptogenic activity induced by intravenous injection of certain cephalosporin derivatives was studied . Ceftezole provided the most potent epileptogenic activity among the drugs tested . Changes in seizure patterns on electroencephalogram (EEG) tracings and behavioral signs after administration of cefotiam and cefazolin were similar to those seen after ceftezole, though the intensity and duration were less than those of ceftezole . Cephacetrile and cephaloridine elicited the spiking activity in the frontal cortex and the other regions without apparent behavioral changes . Latamoxef and cefmenoxime displayed a weak epileptogenic activity at a dose of 1000 mg/kg . On the other hand, cephapirin, cefmetazole and cefoxitin did not evoke any changes in EEG nor in behavior . Penicillin G at a dose of 200 mg/kg affected spike or spike-and-wave complex in a few cases, but at a dose of 500 mg/kg the animals died of dyspnea almost immediately after injection without showing apparent epileptogenic signs . These results suggest that some of cephalosporins such as ceftezole, cefotiam, cephacetrile and cefazolin provide epileptogenic activity at higher doses. Chest, 1984 Jul, 86(1), 138 - 40 Cephalosporin-induced interstitial pneumonitis; Dreis DF et al.; This report describes a patient who developed dyspnea and bilateral pulmonary infiltrates following exposure to cephradine . The role of cephradine was substantiated by rechallenge. Arch Intern Med, 1984 Jul, 144(7), 1392 - 7 Management of pneumonia in the prospective payment era . A need for more clinician and support service interaction; Dans PE et al.; We compared the diagnostic and therapeutic management of pneumonia during 1970 and 1971 with that during 1979 and 1980 in clinically similar populations at The Johns Hopkins Hospital, Baltimore . More patients received aminoglycoside and cephalosporin therapy during 1979 and 1980 . Guidelines for the use of chest roentgenograms and cultures were exceeded in 14% to 24% of cases . Patients whose cases were judged to be suboptimally managed had significantly higher charges and length of stay . Aged patients and those requiring thoracentesis also used resources more intensively . Given the technologic explosion, clinicians cannot know the performance characteristics of all tests and medications they can order . To minimize inefficient and ineffective practices, it is essential that clinicians and support service directors develop guidelines for testing and antibiotic use . Deviations should trigger timely interventions . Management under prospective payment will also require identifying specific patient subgroups to verify appropriate utilization and to assure equitable reimbursement. Antibiotiki, 1984 Jul, 29(7), 488 - 90 {A number of sorbents useful for the sorption of cephalosporin C}; Kliueva LM et al.; The physicochemical and sorption properties of a number of sorbents made in the USSR and abroad were studied with respect to the recovery of cephalosporin C from a model solution . It was shown that the sorption capacity of a sorbent depended on its specific surface . The macroporous styrene divinylbenzene sorbents with a specific surface of more than 500 m2/g had the best sorption properties. Clin Pharmacol Ther, 1984 Jun, 35(6), 798 - 803 Cefonicid kinetics in subjects with normal and impaired renal function; Blair AD et al.; Cefonicid is a cephalosporin with a longer t1/2 than currently available cephalosporins . Cefonicid kinetics after an intravenous dose of 7.5 mg/kg were followed in four groups of subjects: group 1, four subjects with normal creatinine clearance (Clcr greater than 80 ml/min); group II, seven subjects with mild renal insufficiency (Clcr 50 to 80 ml/min); group III, five subjects with moderate to severe renal impairment (Clcr 8 to 49 ml/min); and group IV, five subjects with end-stage renal disease who were receiving maintenance hemodialysis (Clcr less than 8 ml/ml) . Cefonicid volume of distribution ranged from 6.9% to 17.6% body weight but was not related to Clcr . Elimination t1/2 was 4.6 +/- 0.7 hr in group 1,6.0 +/- 2.7 hr in group II, 25.6 +/- 14.0 hr in group III, and 65.3 +/- 43.6 hr in group IV . There was a strong correlation between plasma cefonicid clearance and Clcr . Nonrenal clearance did not change with decreasing Clcr . Hemodialysis clearance calculated from plasma concentrations and recovery in dialysate was 2.5 +/- 0.9 ml/min . These kinetic parameters were used to formulate dosage regimens for patients with renal impairment. Antibiotiki, 1984 Jun, 29(6), 427 - 30 {Cephalosporin and carbenicillin penetration into the tissues of rats with aseptic inflammation}; Agapitova IV et al.; Two beta-lactam antibiotics with different serum protein binding were studied for penetration into the tissues of rats with aseptic inflammation . It was found that the pharmacokinetics of the drugs in the blood serum differed only in the elimination rate . The levels of the free fraction of cephaloridin were much higher than those of carbenicillin . The maximum concentrations of free cephaloridin in the inflammation exudate, intact and inflamed tissues and the areas under its pharmacokinetic curves were higher than those of carbenicillin . The elimination rate of both the drugs was the same for all the tissues studied. J Med Chem, 1984 May, 27(5), 694 - 700 Substituent effects on reactivity and spectral parameters of cephalosporins; Coene B et al.; The chemical reactivity of a series of cephalosporins is examined as a function of the substituents at positions 3 and 7 . In most cases, the nature of the C7 side chain has a minor influence on the beta-lactam reactivity . But in the case of amino-containing C7 substituents, when intramolecular nucleophilic attack may occur, the reactivity may be greatly increased . The spectroscopic and structural characteristics of the beta-lactam linkage do not correlate with the chemical reactivity of studied compounds . The hydrolysis rates are linked neither with the IR frequency or 13C NMR chemical shift of the carbonyl beta-lactam nor with the geometry of the beta-lactam ring . However, a relationship is confirmed between the beta-lactam ring opening rate and the polarity of the C3-C4 double bond, reflected in the different 13C NMR chemical shifts of those atoms . The results are an experimental verification of the theoretical calculations of Boyd et al . on cephalosporin model compounds, which foresee that a C3 substituent could favor the opening of the beta-lactam cycle by stabilizing a transition state involved in alkaline hydrolysis. Pathol Biol (Paris), 1984 May, 32(5), 335 - 7 {Passage of ceftriaxone in the aqueous humor and tears . Comparison with other beta-lactams}; Mounier M et al.; The intraocular distribution of ceftriaxone (a new cephalosporin of the third generation) was studied in 33 patients undergoing cataract surgery . The mean level of antibiotic in the aqueous humor was of 0,53 micrograms/ml (1.25% of the serum level), in the tears show an average rate of 5.75 micrograms/ml (13% of the serum level) was found . A study of the kinetics in the tears shows increasing levels for the first 18th hours. J Pharm Sci, 1984 May, 73(5), 611 - 8 Degradation kinetics in aqueous solution of cefotaxime sodium, a third-generation cephalosporin; Fabre H et al.; The degradation kinetics of a 3- acetoxymethylcephalosporin , cefotaxime sodium salt, in aqueous solution investigated by HPLC under different conditions (pH, ionic strength, temperature) and using different buffers . The scheme of degradation involves a cleavage of the beta-lactam nucleus and the deacetylation of the side chain . In highly acidic medium, the deacetylated derivative is easily converted to the lactone . The degradation rate constants were calculated at three pH values (1.9, 4.0, and 9.0) by measuring the residual cephalosporin and the main decomposition products . The degradation pathway is both supported by the results of a primary salt effect and by the agreement between the theoretical pH-rate profile and the experimental values . In the pH range from 3.0 to 7.0, the main process is a slow water-catalyzed or spontaneous cleavage of the beta-lactam nucleus with intramolecular participation of the side chain amido fraction in the 7-position . In alkaline or strongly acidic medium, the hydrolysis is a base- or acid-catalyzed reaction . Of the buffer systems investigated, carbonate buffer (pH 8.5) and borate buffers (pH 9.5 and 10.0) are found to increase the degradation rates, while acetate buffer decreases the degradation rates . The apparent activation energies determined at different pH values are compatible with a solvolysis mechanism and similar to those previously given in the literature for other cephalosporins . Cefotaxime in aqueous solution is slightly less stable than the main cephalosporin derivatives, despite its high resistance to the beta-lactamases and its remarkable biological activity. Jpn J Antibiot, 1984 May, 37(5), 787 - 90 {Clinical studies on cefmenoxine concentration in prostatic tissue and bladder wall}; Miyagawa I et al.; Clinical studies on cefmenoxime (CMX) concentration in prostatic tissue and bladder wall were made and the following results were obtained . In 40 patients undergoing operation, 1 g of CMX was administered intravenously by bolus technique and CMX levels in peripheral blood, prostatic tissue and bladder wall were examined . The maximum level of prostatic tissue was 35 micrograms/g after 0.41 hour and bladder wall was 62 micrograms/g after 0.37 hour, and T1/2 was 1.41 hours both . CMX, a new broad spectrum cephalosporin, can be considered as one of the highly useful antibiotics for the treatment of postoperative infection. J Biol Chem, 1984 Apr 25, 259(8), 5327 - 32 Purification and properties of thiol beta-lactamase . A mutant of pBR322 beta-lactamase in which the active site serine has been replaced with cysteine; Sigal IS et al.; The specifically mutated enzyme thiol beta-lactamase has been expressed in Escherichia coli by means of the trp promoter and purified to homogeneity . The gene for this enzyme results from a single base change N410 A----T in the gene of pBR322 RTEM beta-lactamase (EC 3.5.2.6, penicillinase, penicillin amido-beta-lactamhydrolase) which alters the codon for the active site Ser 70 to that for Cys . Precursor thiol beta-lactamase is processed to give the same NH2-terminal sequence as that for wild type enzyme . In contrast to the wild type enzyme, thiol beta-lactamase contains one free titratable thiol group/molecule . Thiol beta-lactamase catalyzes the hydrolysis of beta-lactams with a substrate specificity that is distinct from that of wild type enzyme . For benzyl-penicillin and ampicillin, the Km values are similar to wild type values although the kcat values are 1-2% that of wild type enzyme . For the cephalosporin nitrocefin, the Km is greater than 10-fold that of the wild type and the kcat is at least as large as the kcat for the wild type enzyme . Thiol beta-lactamase is different from wild type beta-lactamase in that it is not competitively inhibited by boric acid although a small degree of noncompetitive inhibition does occur . Whereas the circular dichroism spectra of both enzymes are nearly identical, thiol beta-lactamase at 40 degrees C is 3-fold more resistant to trypsin than is the wild type enzyme. Arch Ophthalmol, 1984 Mar, 102(3), 435 - 8 Moxalactam retinal toxicity; Fett DR et al.; Moxalactam disodium is a new third-generation semisynthetic, broad-spectrum, cephalosporin-like antibiotic for parenteral administration . Topical, subconjunctival, and intravenous administration provide poor concentration in the vitreous . To determine its toxicity in intravitreal administration, we injected comparative doses directly into the vitreous cavity of 21 rabbits . With doses of 1.25 mg or less there was no toxic damage to the retina . With a dose of 2.5 mg, early degeneration of photoreceptors was seen after three months . With higher doses (5 and 10 mg) there were major histopathologic and electroretinographic changes . These results suggest the feasibility of employing moxalactam in the treatment of acute, severe, fulminant bacterial endophthalmitis. Antimicrob Agents Chemother, 1984 Mar, 25(3), 336 - 8 Liquid chromatographic assay of ceftizoxime in sera of normal and uremic patients; McCormick EM et al.; The application of high-pressure liquid chromatography assays for cephalosporin serum concentrations is difficult in uremic patients because of interference from nondialyzable substances . We developed a high-pressure liquid chromatography method for determining the serum concentration of ceftizoxime in normal and uremic patients . The method involves protein precipitation with acetonitrile, followed by removal of the acetonitrile with dichloromethane . Separation was accomplished with a reverse-phase (C-18) column and a mobile phase of 13% acetonitrile and 2.8% acetic acid . UV detection at 310 nm was used to monitor the peaks . This assay produced a linear relationship between peak height ratio and ceftizoxime concentration from 1.5 to 100 micrograms/ml . Samples from 30 patients were assayed by this method and by a bioassay, with a good correlation of results (r = 0.9832) . The method was applicable equally to normal and uremic serum samples. Pediatr Med Chir, 1984 Mar-Apr, 6(2), 277 - 80 {Treatment of acute respiratory infections in childhood with a new cephalosporin, ceftriaxone}; Berni Canani M et al.; Results of the comparison between tobramicine and ceftriaxone (new long-acting 3rd generation cephalosporin) in the treatment of pediatric acute respiratory tract infections are referred . Treatment with ceftriaxone is judged more advantageous both for efficacy and for saving the number of administered doses. Hosp Pharm, 1984 Mar, 19(3), 202, 207, 211 - 3 Stability of cephapirin sodium admixtures after freezing and conventional or microwave thaw techniques; Hilleman DE et al.; The freeze-microwave thaw technique has important advantages compared with conventional piggyback delivery systems . A requirement for the implementation of this technique, however, is the documentation of antibiotic stability following freezing and microwave thawing . The purpose of this study was to assess the stability of a commonly used cephalosporin, cephapirin sodium, following freezing and conventional or microwave thawing . This data was not previously available . Cephapirin sodium was admixed with either 5% dextrose injection or 0.9% sodium chloride injection in polyvinylchloride minibags at concentrations of 10 and 40 mg/ml and then frozen for 14 days . Admixtures were then thawed conventionally or by microwave heating . Cephapirin concentrations were determined spectrophotometrically after reconstitution, immediately after thawing, and 6, 12, and 24 hours after thawing . No significant differences in admixture potency after reconstitution, immediately after thawing, or at 6, 12, and 24 hours after thawing were observed when thaw techniques were compared . All admixtures retained at least 90% of labeled content regardless of thaw technique, type of diluent, or initial concentration . In addition, all admixtures retained at least 90% potency 24 hours after thawing when compared with the actual concentration determined immediately after reconstitution . The rate of cephapirin degradation was not influenced by thaw technique, type of diluent, or initial admixture concentration . The results of this study suggest that cephapirin sodium may be added to the list of drugs capable of withstanding freeze-microwave thaw treatment. J Antimicrob Chemother, 1984 Feb, 13(2), 191 - 6 The absolute bioavailability of oral cefuroxime axetil in male and female volunteers after fasting and after food; Williams PE et al.; Cefuroxime axetil is a novel oral cephalosporin . Two studies are described in which fasting male and female volunteers were given single oral doses of 1 g cefuroxime axetil in comparison with intravenous cefuroxime, and in which absorption was compared in the fasting and non-fasting states . The mean (and range) absolute bioavailability of cefuroxime axetil in the first study was 0.35 (0.26-0.44) in male volunteers and 0.32 (0.23-0.41) in female volunteers . In the second study, the bioavailability was significantly greater when cefuroxime axetil was given after food: 0.45 (0.34-0.55) in males and 0.41 (0.29-0.51) in females . There were no differences between the pharmacokinetics of cefuroxime axetil in males and females . It is recommended that patients take doses of cefuroxime axetil shortly after food. Eur J Biochem, 1984 Jan 2, 138(1), 83 - 7 Study of the Zn-containing DD-carboxypeptidase of Streptomyces albus G by small-angle X-ray scattering in solution; Labischinski H et al.; Study of the Zn2+-containing D-alanyl-D-alanine-cleaving carboxypeptidase of Streptomyces albus G by small-angle X-ray scattering in solution yielded the following molecular parameters: radius of gyration R = 1.82 +/- 0.05 nm; largest diameter D = 5.9 +/- 0.2 nm; relative molecular mass Mr = 17000 +/- 2000; volume V approximately equal to 35 +/- 2 nm3; degree of hydration: 0.25 +/- 0.02 g water/g protein . By reference to theoretical scattering curves of rigid triaxial homogeneous bodies, a model which fits all experimental data is an elliptical cylinder . Such a model is compatible with that observed in the crystal structure . At those high concentrations necessary to form inactive enzyme-ligand associations the non-competitive beta-lactam inhibitors, cephalothin and cephalosporin C, drastically altered the scattering behaviour of the protein. Antimicrob Agents Chemother, 1984 Jan, 25(1), 88 - 92 Mechanism of action of AC-1370 on phagocyte functions; Ohnishi H et al.; The mechanism of action of a new semisynthetic cephalosporin AC-1370 on phagocyte functions was investigated . AC-1370 enhanced phagocytic functions of macrophages and neutrophils . AC-1370 bound to 27.4% of mouse peritoneal resident cells . Most of the AC-1370-binding cells were macrophages, and few neutrophils bound AC-1370 . Culture supernatant of mouse macrophages cultured with AC-1370 significantly augmented phagocytic functions of mouse neutrophils . This activity of the culture supernatant of AC-1370-stimulated macrophages was abolished by digestion with trypsin but not by heat treatment at 56 degrees C for 30 min . The mechanism of the activation of phagocyte functions by AC-1370 is proposed as follows . First, AC-1370 binds to macrophages and causes their activation . Second, trypsin-sensitive and heat-stable soluble factor(s) is released from these macrophages . And finally, neutrophil functions are activated by the factor(s). Jpn J Antibiot, 1984 Jan, 37(1), 6 - 13 {Experience with ceftazidime in the field of obstetrics and gynecology}; Kohara T et al.; Ceftazidime ( CAZ ), a new cephalosporin antibiotic, was studied for transference into tissues and clinical efficacy in the field of obstetrics and gynecology, and the following results were obtained: After one shot intravenous injection of CAZ 1 g, favourable transference of CAZ into uterine tissues was observed . While the mean serum level at 1 hour after the administration was 50.2 micrograms/ml, the levels in oviduct, ovary, endometrium, myometrium, cervix uteri and portio vaginalis were 25.9, 31.6, 24.9, 24.5, 34.2 micrograms/g and 40.6 micrograms/g, respectively . The half-life of CAZ in these tissues ranged from 1.16 to 1.65 hours while that in serum was 1.24 hours . The peak level in retroperitoneal space exudate (25.3 micrograms/ml) was obtained at 3 hours after one shot intravenous injection of CAZ 1 g . The level was still as high as 2.68 micrograms/ml even 12 hours after the administration . Out of 4 cases of obstetric and gynecological infections, 3 cases were assessable, CAZ was effective in these 3 assessable cases . Neither adverse effects nor abnormalities in laboratory findings due to CAZ were observed . Based on these results, CAZ is considered to be an highly effective antibiotic with good transference into uterine tissues and clinical efficacy in obstetric and gynecological infections. Jpn J Antibiot, 1984 Jan, 37(1), 33 - 7 {Fundamental and clinical studies on ceftazidime in the field of obstetrics and gynecology}; Horii T et al.; Fundamental and clinical studies were carried out on ceftazidime ( CAZ ), a new cephalosporin antibiotic, with the following results . Following each 1.0 g of drip infusion and bolus intravenous injection, transfer of CAZ to the internal genital organs was found to be good . Transfer of CAZ into exudate of the pelvic dead space was also good . CAZ was given to 6 cases . Clinical efficacy was good in 5 cases and poor in 1 case . No side effects were observed in any case . The above results demonstrated that CAZ is a safe and effective drug. Jpn J Antibiot, 1984 Jan, 37(1), 28 - 32 {Fundamental and clinical studies of ceftazidime in the field of obstetrics and gynecology}; Shintani M et al.; Ceftazidime ( CAZ ), a new cephalosporin antibiotic, was fundamentally and clinically studied . The following results were obtained . Serum and internal genital tissue levels of CAZ were measured following intravenous drip infusion of 1 g for 30 minutes . Serum levels of more than 10 micrograms/ml and tissue levels of more than about 7 micrograms/ml were maintained after 2 hours to 2 hours and 30 minutes, respectively . Favourable transfer of CAZ into the pelvic dead space exudate was observed . The exudate level attained its peak of 31.54 micrograms/ml on average at 2 hours and was 16.8 micrograms/ml on average even at 8 hours after intravenous drip infusion . A total of 6 cases comprising 1 of adnexitis, 2 of pyometra, 1 of endometritis and 2 of parametritis was treated with CAZ at a dose of 0.5 approximately 2.0 g twice daily by intravenous injection or intravenous drip infusion . The clinical response was excellent in 1 case, good in 4 cases and poor in 1 case . Abnormal laboratory findings and side effects due to the drug were not noted. Sex Transm Dis, 1984 Jan-Mar, 11(1), 28 - 9 Laboratory-acquired gonococcal conjunctivitis: successful treatment with single-dose ceftriaxone; Zajdowicz TR et al.; Gonococcal conjunctivitis can be a severe disease with sequelae of corneal ulceration, hypopyon, and global perforation . Current recommended therapy is hospitalization and repeated courses of parenteral antibiotics . The authors report a case successfully managed with a single injection of the new third-generation cephalosporin, ceftriaxone. Chemotherapy, 1984, 30(4), 221 - 6 Biliary excretion of ceftizoxime in humans; Brogard JM et al.; Biliary concentrations of a new cephalosporin, ceftizoxime, were measured in bile collected in 8 cholecystectomized patients provided with T-tube drainage and in 14 patients where bile was obtained by puncture of the gall bladder and choledochus during cholecystectomy . In patients with external biliary drainage, a mean biliary peak of 150.3 +/- SEM 49.8 micrograms/ml has been observed 2 h after intravenous injection of 2 g of ceftizoxime; the antibiotic activity amounted still to 17.3 +/- 6.0 micrograms/ml after 6 h . Assays performed during operation showed the following simultaneous concentrations 1 h after 2 g of ceftizoxime given intravenously: serum: 85.3 +/- 8.1 micrograms/ml; main duct bile: 279.8 +/- 40.0 micrograms/ml; gallbladder bile: 119.9 +/- 19.4 micrograms/ml . These findings were compared with the biliary excretion of 8 other cephalosporins studied previously under the same conditions . The results of the present study suggest that administration of ceftizoxime may be effective in the treatment of biliary tract infections. Schweiz Med Wochenschr, 1983 Dec 10, 113(49), 1860 - 3 {Effect of various types of liver diseases on the behavior of cefoperazone}; Male PJ et al.; Cefoperazone is a third generation cephalosporin mainly excreted by the biliary route . Hepatic dysfunction may have a pronounced effect on its pharmacokinetic behaviour . Sixty liver patients (acute viral hepatitis, alcoholic fatty liver and liver cirrhosis), without overt renal disease, have been studied and compared to controls . In liver disease the total clearance of cefoperazone is markedly decreased by reduction of extrarenal clearance, which is variable for each type of liver injury . Renal clearance does not change or may even increase, when hypoalbuminemia is present and compensates the reduction in extrarenal clearance. Jpn J Antibiot, 1983 Dec, 36(12), 3463 - 75 {Basic and clinical studies on ceftazidime in the field of obstetrics and gynecology}; Cho N et al.; Ceftazidime (CAZ), a new cephalosporin antibiotic, was studied in the field of obstetrics and gynecology, and the following results were obtained . The absorption and tissue penetration of CAZ into intrapelvic genital organs were good after a single drip infusion of 1.0 g for 30--60 minutes . The maximum level of 76.4 micrograms/ml was obtained in uterine artery serum at 8 minutes after administration . The high concentrations were also obtained in genital tissues; the maximum concentrations ranged from 46.8--62.1 micrograms/g at 20 minutes after administration and the levels were as high as 2.1--7.7 micrograms/g at 5 hours and 40 minutes after administration . The concentration curves in tissues were consistent with those of serum levels . The concentrations of CAZ in retroperitoneal dead space exudate were determined after intravenous drip infusion of 1 g . The peak levels ranged from 26 to 32 micrograms/ml after 30 minutes of administration and the level of 8.53 micrograms/ml was sustained even 6 hours later . Good response was obtained in cases of gyneco-obstetric infections such as intrauterine infection, intrapelvic infection and external genital infection with daily dose of 2--4 g . CAZ was effective in 13 out of 14 cases (the efficacy ratio; 92.9%) . As to side effects, gastric discomfort and vomiting were observed in 1 case. An Esp Pediatr, 1983 Dec, 19(6), 444 - 51 {Treatment of type-b H . influenzae meningitis resistant to ampicillin and chloramphenicol}; Escribano A et al.; Three cases of H . influenzae type b meningitis with resistance to ampicillin and cloramphenicol are described . All infants were treated with new cephalosporin derivates . CSF sterilization was achieved in all patients . Clinical evolution was good in the two old infants treated with cefotaxime, nevertheless younger infant treated with cephoxitin developed serious neurologic and psychologic sequelae . H . influenzae b was erradicated of a carrier mother after four days of rifampicin therapy . Finding of multiple-resistance H . influenzae type b meningitis and therapeutics problems are emphasized by authors. J Hyg (Lond), 1983 Dec, 91(3), 421 - 7 A cephalosporin active in vivo against Nocardia: efficacy of cefotaxime in murine model of acute pulmonary nocardiosis; Sugar AM et al.; Cefotaxime, a cephalosporin drug, has been shown to be active in vitro against nocardiae, a finding confirmed in this study . Pharmacokinetic studies were performed in mice to define regimens which provided peak serum levels comparable to that achieved in man with currently used doses . These regimens were shown to be effective with only short courses of therapy of rapidly progressive and highly lethal N . asteroides infection, produced by pulmonary challenge of mice . This suggests the possible utility of this drug in human nocardiosis. Pediatr Infect Dis, 1983 Nov-Dec, 2(6), 424 - 5 "Cephalomalacia obfuscate," a fourth generation cephalosporin; Rubin BK; A new fourth generation cephalosporin, cephalomalacia obfuscate, has been synthesized . Limited testing has shown this new class of antibiotic to have substantially greater bacteriopathic properties than the third generation antibiotics . The role that these properties may play in host defense is discussed. Arch Surg, 1983 Nov, 118(11), 1259 - 61 Moxalactam . Evaluation of clinical bleeding in patients with abdominal infection; Joehl RJ et al.; Previous clinical studies have emphasized that hypoprothrombinemia may occur during treatment with moxalactam disodium, a new broad-spectrum cephalosporin . Usually, this abnormality is corrected by administering vitamin K . Recent case reports have described bleeding complications associated with moxalactam therapy and suggested that platelet function is depressed by this drug . We studied eight patients with abdominal infection who were treated with moxalactam . Six of them had prolonged template bleeding times, and two had clinically significant hemorrhage (epistaxis, hematuria, and rectal bleeding) during treatment with moxalactam . These observations suggest that coagulation studies and template bleeding times should be monitored during moxalactam therapy, especially before major surgery. J Trauma, 1983 Nov, 23(11), 1012 - 4 Successful venomous snakebite neutralization with massive antivenin infusion in a child; Buntain WL; Intravenous antivenin requirements to neutralize venomous snake bites can be appropriately calculated based on accurate estimations of injury severity, and/or safely titrated if systemic symptoms are present . This report describes a case in a child given 13 10-ml vials of crotalidae antivenin before and during transfer, and tetanus prophylaxis, cephalosporin (200 mg IV q 6 h), and the titration of 62 additional 10-ml vials of antivenin within 14 hours, based on the child's response to therapy . By the tenth day all symptoms had resolved. Clin Chem, 1983 Nov, 29(11), 1934 - 6 Concurrent measurement of theophylline and caffeine in neonates by an interference-free liquid-chromatographic method; Ou CN et al.; A sensitive liquid-chromatographic method was developed for the simultaneous measurement of theophylline and caffeine within 6 min . The excellent resolution of the method allows the complete separation of theophylline, internal standard, and caffeine from frequently encountered interfering drugs including acetaminophen, acetazolamide, acetylsalicylate, ampicillin, 8-chlorotheophylline, cefazolin, cephalosporin C, cephalothin, cephapirin, chloramphenicol, dyphylline, metronidazole, 3-methylxanthine, salicylate, sulfadiazine, sulfamerizine, sulfamethazine, sulfamethoxazole, sulfisoxazole, and theobromine . The chromatographic system involves a Waters' Radial-Pak C18 reversed-phase column and acetonitrile in 0.1 mol/L potassium phosphate buffer, pH 4.0, (9.5/90.5 by vol) as the mobile phase . The method can detect theophylline or caffeine concentrations as low as 0.5 mg/L in 50 microL of serum . Precision and accuracy are excellent. Clin Pharmacol Ther, 1983 Nov, 34(5), 673 - 80 Ceftizoxime elimination kinetics in continuous ambulatory peritoneal dialysis; Gross ML et al.; We investigated the kinetics of ceftizoxime, a beta-lactamase stable cephalosporin, in eight subjects undergoing continuous ambulatory peritoneal dialysis (CAPD) . A single 500-mg or 1-gm dose was injected IV, or a 500-mg dose was given intraperitoneally in the CAPD fluid during a 6-hr dwell time . The ceftizoxime (500 mg) serum kinetic parameters were as follows: peak concentrations, 21 to 46 mg/l; volume of distribution, 0.27 l/kg; elimination rate constant, 0.0784 hr-1; plasma clearance, 1.66 l/kg hr-1; and t1/2, 10.2 hr . The t1/2 after 1 gm was 12 hr . Dialysate ceftizoxime concentrations rose rapidly between 0.25 and 2 hr and slowly over the next 4 hr, but only 4.04 +/- 1.8 and 7.4 +/- 2.9 mg ceftizoxime/hr was eliminated by the peritoneal route over a 6-hr dwell time after 500 mg or 1 gm IV . This represents only 4% to 5% of the dose . After intraperitoneal instillation, the antibiotic appeared in the serum within 15 min in all four subjects, and the peak serum concentrations ranged from 12 to 19.8 mg/l (mean +/- SD = 16.4 +/- 3.3) between 5 and 6 hr . Approximately 78% of ceftizoxime was absorbed from the peritoneal dialysis fluid during a single 6-hr dwell time . Rate constant for absorption, ka, was 0.3959 hr-1 and absorption t1/2 was 1.75 hr (as calculated by the residual equation) . These data suggest that ceftizoxime has bidirectional exchange characteristics through the peritoneal membrane . Instillation of ceftizoxime in CAPD fluid alone may permit rapid absorption to reach therapeutic serum concentrations. Antibiotiki, 1983 Oct, 28(10), 755 - 7 {Effect of experimental cefuroxime on the immunologic reactivity of the body}; Chernushenko EF et al.; The effect of ketocef or cefuroxim, a new cephalosporin antibiotic, on the immune system was studied on mice . The repeated use of the drug for 10 days a dose of 30 mg/kg injected intramuscularly did not result in suppression of the immune status . The number of the rosette forming cells of the thymus and spleen did not change . The production of hemolysin as shown by the number of the antibody forming cells somewhat increased, when the animals were immunized with the sheep red blood cells . A certain decrease in the intensity of the anaphylactic reaction was observed in sensitization of the animals with bovine serum. J Clin Pharmacol, 1983 Oct, 23(10), 473 - 83 Specificity of renal tubular damage criteria for aminoglycoside nephrotoxicity in critically ill patients; Schentag JJ; Two populations of critical care patients were studied using indices of renal tubular damage (beta 2-microglobulin, enzymes, casts) and indices of glomerular filtration (creatinine, creatinine clearance) . The purpose of these studies had been initially to elucidate the type of renal failure typical of the critically ill patient treated with aminoglycoside gentamicin or tobramycin, then to determine its frequency . The second study population included a control group of patients given the nonnephrotoxic cephalosporin moxalactam, in order to assess the specificity of the renal tubular damage criteria for aminoglycoside nephrotoxicity versus other types of renal injury in critical care patients . Creatinine rise occurred in approximately 30 per cent of each tobramycin-treated group and in only 12 per cent in the moxalactam control patients (P less than 0.05) . Thus, the data indicate that aminoglycosides are associated with an approximate doubling of the renal damage in those older, critically ill patients . Renal tubular damage criteria appear specific for the aminoglycoside effect, but a substantial percentage of the renal damage in this population is not associated with detectable alterations in renal tubular status. Jpn J Antibiot, 1983 Oct, 36(10), 2671 - 4 {Clinical study of diffusion of cefotiam into myocardial tissue}; Hibi M et al.; In 11 patients undergoing open-heart operation, 1 g of cefotiam (CTM) was administered intravenously by bolus technique at the start of operation . Samples of serum were obtained at 30, 60 and 90 minutes following administration . Samples of right atrial appendage tissue and serum were obtained simultaneously at the time of heart cannulation . Antibiotic concentrations of all samples were determined by agar well method using P . mirabilis ATCC21100 as the test organism . The results were as follows: Serum levels of CTM after 30, 60 and 90 minutes were 53.1 +/- 17.6 micrograms/ml (Mean +/- S.D., n = 10), 26.1 +/- 10.4 micrograms/ml (n = 11) and 13.5 +/- 5.5 micrograms/ml (n = 7) respectively . Myocardial tissue levels of CTM after 60 and 90 minutes were 9.4 +/- 4.7 micrograms/g (n = 4) and 4.8 +/- 2.7 micrograms/g (n = 7) respectively . The concentration ratios of the myocardial tissue to serum were 0.36 +/- 0.10 (n = 4) after 60 minutes and 0.35 +/- 0.09 (n = 7) after 90 minutes . CTM can transmigrate from blood to myocardial tissue easily as compared with other cephalosporins . Therefore, CTM, a new broad spectrum cephalosporin, can be considered as one of the highly useful antibiotics for the prevention and treatment of infections following cardiac operation. Clin Orthop, 1983 Sep, (178), 36 - 41 Considerations in reducing the infection rate in open tibial fractures; Patzakis MJ et al.; During the period from 1979 to 1980, 109 patients with open tibial fractures were treated by a cephalosporin and an aminoglycoside, and by saline and topical antibiotic wound irrigation; partial closure was used for Types I and II open tibial wounds, and all Type III wounds were left open . Stabilization was accomplished by plaster alone, external pins in plaster, or an external fixator with full transfixion pins . The overall infection rate was 4.5% (5 of 109 wounds) in this study . This represents a significant reduction from the previous infection rate of 14% in 254 open tibial fractures treated by the authors in previous years by all methods. Jpn J Antibiot, 1983 Sep, 36(9), 2549 - 55 {Clinical evaluation of cefroxadine in the field of obstetrics and gynecology}; Uchida S et al.; Cefroxadine (CXD), an oral cephalosporin antibiotic was studied in the field of obstetrics and gynecology and the following results were obtained . CXD was orally given to 22 cases at daily dose of 1,500 mg 3 times a day . CXD administration was given to 22 cases in all; 4 with cervicitis, 6 with endometritis, 2 with puerperal fever, 4 with bartholinitis, 5 with adnexitis and 1 with vulvitis, respectively . Overall efficacy rate was 77.3% (17/22) (excellent 4, good 13, fair 5) . As for side effects, a slight diarrhea was observed . CXD was considered to be a useful antibiotic in the field of obstetrics and gynecology by above the results. Jpn J Antibiot, 1983 Sep, 36(9), 2529 - 34 {Clinical effect and transfer into the wound exudate of cefroxadine used in the treatment of soft tissue infection}; Takata N et al.; Clinical effect and excretion into wound exudate of a new semisynthetic cephalosporin cefroxadine (CXD), were studied . CXD was given in 25 cases of surgical infections; 6 cases of wound infection, 9 cases of abscess, 9 cases of infected atheroma and 1 case of furuncle . CXD was orally administered in daily dose of 750 to 1,500 mg . Clinical results were excellent in 1 case, good in 18 cases, fair in 3 cases and poor in 3 cases . The overall clinical efficacy rate was 76.0% . Clinical efficacy classified by diagnosis was 66.7% in wound infection, 66.7% in abscess, 88.9% in infected atheroma, and 100% in furuncle . Side effects were not observed in all cases among 25 patients in CXD trials . Studies of excretion into wound exudate of CXD were performed in 1 postoperative case of mamma carcinoma after oral administration of 500 mg of CXD . The concentration of CXD in exudate was 1.12 micrograms/ml in 2 hours, 3.48 micrograms/ml in 3 hours, 4.13 micrograms/ml in 4 hours, 5.56 micrograms/ml in 5 hours and 4.41 micrograms/ml in 6 hours after administration, which was observed that CXD was excreted in wound exudate in high concentration. Jpn J Antibiot, 1983 Sep, 36(9), 2497 - 501 {Clinical experience with cefadroxil in otorhinolaryngological infections}; Iino Y et al.; Cefadroxil (CDX), a new semisynthetic cephalosporin derivative, was administered to 20 patients with acute or chronic otolaryngological infections and following results were obtained . Of 11 cases with acute infections such as acute otitis media, acute otitis externa and postoperative maxillary cyst, excellent, good and fair results were obtained in 10 cases, the efficacy ratio being 91%, while the efficacy ratio in 9 cases with chronic infections such as chronic pharyngolaryngitis and chronic otitis media was 56% . CDX is, therefore, extremely effective for acute otolaryngological infections . No severe side effect was observed, although there were 2 cases with minor adverse effects, one with drug induced eruption and the other with stomatitis. J Hand Surg {Am}, 1983 Sep, 8(5 Pt 1), 563 - 7 Eikenella corrodens in hand infections; Goldstein EJ et al.; Clinical and therapeutic information on 21 patients with hand infection due to Eikenella corrodens is reported . Patients given empiric therapy ineffective against E . corrodens had a high incidence of complications, while proper empiric therapy was associated with good recovery . All hand wounds should be cultured aerobically and anaerobically and empiric antibiotic therapy should include a penicillinase-resistant penicillin or cephalosporin in combination with penicillin G. Am Fam Physician, 1983 Sep, 28(3), 204 - 10 Treating community-acquired lower respiratory infection; Meyers BR; Despite the proliferation of antibiotics, pneumonia remains a leading cause of death in the United States . Diagnostic methods for identifying pathogenic organisms in pneumonia frequently are inaccurate or unreliable, and may be unproductive . When the precise etiology has not been determined, a second-generation cephalosporin offers wide antibiotic coverage as initial therapy for patients with community-acquired bacterial pneumonia. Hosp Pharm, 1983 Aug, 18(8), 416 - 20 Controlling moxalactam and cefotaxime use with a target drug program; Abramowitz PW et al.; A target drug program was utilized to prevent increasing costs associated with inappropriate use of moxalactam and cefotaxime . The cost saving abilities of pharmacists in this regard were calculated . Pharmacists consulted with physicians each time these drugs were prescribed to encourage cefazolin substitution when appropriate . Records of all cephalosporin piggyback doses dispensed were maintained along with quarterly purchase data . Excess costs of utilizing third generation cephalosporins in place of cefazolin were calculated for various usage levels . Actual third-generation usage was compared to usage predicted if no target program was in place, and cost saving was calculated . During the study period, combined moxalactam and cefotaxime use averaged 3.2% of total cephalosporin use at a cost of $4109 per month . Based on an expected predicted usage of 20% to 40%, an annualized cost savings of $91,071 to $202,815 was achieved . Clinical pharmacists were very effective in preventing inappropriate use of moxalactam and cefotaxime, preventing a rise in drug costs. Antimicrob Agents Chemother, 1983 Jul, 24(1), 104 - 6 Comparison of ceftazidime concentrations in bile and serum; Bouza E et al.; Biliary excretion of ceftazidime, a new broad-spectrum cephalosporin, was studied in two groups of patients after administration of a 2-g dose intravenously . Group A included 10 patients in whom ceftazidime levels in bile were measured during cholecystectomy . Group B included 10 patients with indwelling biliary tubes in whom ceftazidime levels in bile and serum were simultaneously measured at 0.5, 1, 2, 4, 6, and 8 h after administration of the drug . Although ceftazidime levels were variable, they exceeded the minimal inhibitory concentrations of most biliary tract pathogens in both groups. J Antimicrob Chemother, 1983 Jul, 12 Suppl A, 27 - 30 Ceftazidime and cefamandole in the treatment of pneumonia; Keeton GR et al.; Fifty-nine community-acquired pneumonias were treated in a randomized double blind trial with cefamandole or ceftazidime . A prospective scoring system was used to define severity . This made use of basic clinical data, associated diseases, white blood count, blood gases and chest radiographs . There were no serious side-effects from the drugs . There were two deaths and six failed treatment . The scoring system which defined an 'ill group' showed as good a response of these ill patients to the new cephalosporin, ceftazidime as to cefamandole. N Engl J Med, 1983 Jun 16, 308(24), 1457 - 63 Improving drug-therapy decisions through educational outreach . A randomized controlled trial of academically based "detailing"; Avorn J et al.; Improving precision and economy in the prescribing of drugs is a goal whose importance has increased with the proliferation of new and potent agents and with growing economic pressures to contain health-care costs . We implemented an office-based physician education program to reduce the excessive use of three drug groups: cerebral and peripheral vasodilators, an oral cephalosporin, and propoxyphene . A four-state sample of 435 prescribers of these drugs was identified through Medicaid records and randomly assigned to one of three groups . Physicians who were offered personal educational visits by clinical pharmacists along with a series of mailed "unadvertisements" reduced their prescribing of the target drugs by 14 per cent as compared with controls (P = 0.0001) . A comparable reduction in the number of dollars reimbursed for these drugs was also seen between the two groups, resulting in substantial cost savings . No such change was seen in physicians who received mailed print materials only . The effect persisted for at least nine months after the start of the intervention, and no significant increase in the use of expensive substitute drugs was found . Academically based "detailing" may represent a useful and cost-effective way to improve the quality of drug-therapy decisions and reduce unnecessary expenditures. J Antibiot (Tokyo), 1983 Jun, 36(6), 700 - 8 Carbon catabolite regulation of the conversion of penicillin N into cephalosporin C; Martin-Zanca DM et al.; Cephalosporin C biosynthesis by Cephalosporium acremonium was delayed until most glucose in the medium was used . Addition of increasing concentrations of glucose up to 55 g/liter decreased cephalosporin C biosynthesis but stimulated growth . Sequential formation of penicillin N (an intermediate in the cephalosporin C biosynthetic pathway) and cephalosporin C was found when the culture was developed synchronously . Little cephalosporin C formation was observed until most penicillin N had already been formed . The sequential formation of penicillin N and cephalosporin C was due to the sequential formation of the "penicillin N synthetase system" and the "cephalosporin C synthetase system" . Cells grown in the presence of glucose showed an increased accumulation of penicillin N and clear reduction of the conversion of penicillin N to cephalosporin C . Resting cell studies indicated that the glucose effect was due to the repression of one or more of the enzymes converting penicillin N into cephalosporin C . Little inhibition by glucose of the activity of these enzymes, once formed, was observed . Glucose did not effect significantly the pool sizes of either precursor amino acids of cephalosporin (alpha-aminoadipic acid and valine) or methionine (an inducer of penicillin N and cephalosporin C biosynthesis) . On the basis of these data it is suggested that glucose catabolism specifically represses the enzyme system converting penicillin N into cephalosporin C. Jpn J Antibiot, 1983 Jun, 36(6), 1435 - 8 {Clinical evaluation of cefroxadine in surgical infections}; Hirayama T et al.; Cefroxadine (CXD), a new cephalosporin, was orally administered to 22 cases in total; 5 with wound infection, 4 with felon, 3 with acute pyelonephritis, 2 with furuncle, 2 with infected atheroma, 2 with phlegmone, 2 with abscess, 1 with acute mastitis, and 1 with lymphadenitis . The daily dose was 500 to 1,000 mg, and maximal total dose and duration was 5 g and 5 days, respectively . Therapeutic results were good in 20 cases (effectiveness rate: 91%), fair in 1 and poor in 1 . No side effect was observed in all cases among 22 patients with CXD. Ther Drug Monit, 1983 Jun, 5(2), 219 - 24 Disulfiram-like reaction to certain cephalosporins; Uri JV et al.; Semisynthetic cephalosporins, containing the methyltetrazolethiol substituent at the 3-position of the fused beta-lactam dihydrothiazine nucleus, can clearly produce disulfiram-like reactions in cert