Cephalosporin

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 certain subjects who consume ethanol after treatment with these cephalosporins . So far, cefamandole, cefoperazone, and moxalactam have been repeatedly reported to produce this reaction, which is strictly related to the chemical structure of the cephalosporin . Similar to the characteristic symptoms and signs observed with disulfiram and these cephalosporins, increased acetaldehyde concentrations in blood were also measured . The phenomenon can be studied in an animal (rat) model . Patients experiencing these often frightening disulfiram-type reactions seldom need specific treatment; however, it is mandatory to strongly caution patients not to consume alcoholic beverages for a few days after treatment with these cephalosporins . Other aspects and ramifications of this phenomenon are also reviewed.

J Pharmacol Exp Ther, 1983 Jun, 225(3), 606 - 10
Effect of cephaloridine on the transport of organic ions in dog kidney plasma membrane vesicles; Kasher JS et al.; The cephalosporin antibiotics cephaloridine and cefazolin were examined for their effects on the transport of a prototype anion, {3H}p-aminohippurate (PAH) and a prototype cation, N1-{3H} methylnicotinamide (NMN) in basolateral membrane vesicles and brush border membrane vesicles (BBMV) . Cefazolin inhibited transport of 50 microM PAH in both membranes and had no effect on transport of 50 microM NMN transport . Under identical conditions, cephaloridine, a zwitterion, inhibited PAH transport in both membranes and NMN transport in BBMV but not in basolateral membrane vesicles . Cephaloridine was less effective than cefazolin in inhibiting PAH transport in BBMV . The results demonstrate the organic transport systems in the basolateral membrane vesicles differ from those in the BBMV . Furthermore, a zwitterionic drug can interact with both systems in the BBMV . An explanation for the intracellular accumulation of cephaloridine is presented.

Clin Orthop, 1983 May, (175), 218 - 22
The effect of hypotensive anesthesia on cephalosporin concentrations in serum, soft tissue, and bone; Ritter MA et al.; The objective of this study was to determine the efficacy of a hypotensive anesthetic in enhancing tissue perfusion while simultaneously controlling surgical blood loss . One hundred ten patients undergoing 126 total hip arthroplasties were administered either cephalothin or cefamandole on a double-blind basis . Hypotensive anesthesia was administered to 64 patients; 46 received a normotensive anesthetic . Degree of tissue perfusion was measured by the concentration of cephalosporin found in samplings of serum, soft tissue, and bone . These samples, obtained during the course of total joint arthroplasty, indicate that the hypotensive anesthetic sodium nitroprusside did not significantly alter the concentrations of cefamandole or cephalothin from those found in the normotensive group.

Clin Chem, 1983 May, 29(5), 856 - 8
Liquid-chromatographic determination of cephalosporins and chloramphenicol in serum; Danzer LA; A "high-performance" liquid-chromatographic technique involving a radial compression module is used for measuring chloramphenicol and five cephalosporin antibiotics: cefotaxime, cefoxitin, cephapirin, and cefamandol . Serum proteins are precipitated with acetonitrile solution containing 4'-nitroacetanilide as the internal standard . The drugs are eluted with a mobile phase of methanol/acetate buffer (30/70 by vol), pH 5.5 . Absorbance of the cephalosporins is monitored at 254 nm . Standard curves are linear to at least 100 mg/L . The absorbance of chloramphenicol is monitored at 254 nm and 280 nm, and its standard curve is linear to at least 50 mg/L . The elution times for various other drugs were also determined, to check for potential interferents.

Antibiotiki, 1983 Apr, 28(4), 289 - 94
{Experimental study of the dynamics of the biochemical indices of the lymph after kefzol and amphotericin B administration}; Polosova RG et al.; Antibiotics belonging to different groups i . e . amphotericin B of the neoaromatic group of heptaene antibiotics and kefzol, a cephalosporin antibiotic were studied with respect to their effect on some biochemical indices of the lymph and blood serum of experimental animals . Amphotericin B was administered intravenously in a dose of 1000 unit/kg once or daily for 5 days . Kefzol (sodium cephazoline) was administered intramuscularly in a single dose of 100 mg/kg . When the antibiotics were used in single doses, the lymph samples were collected from the thoracic duct 1 and 24 hours after the administration . On the repeated use of the antibiotic the samples were collected 24 hours after the last injection . The following biochemical indices were determined: the level of total protein, the ratio of the protein fractions (albumins, alpha 1-, alpha 2, beta- and gamma-globulins), the contents of urea, urea nitrogen, residual nitrogen, total, free and bound cholesterol . The esterification and albumin-globulin coefficients were estimated . The study revealed an analogy in the character of the changes in the above indices of the lymph and blood serum of the rabbits . However, there were also less pronounced changes in the above indices of the blood serum as compared to those in the lymph of the same animals.

Am J Hosp Pharm, 1983 Apr, 40(4), 619 - 23
Particulate matter in four reconstituted cephalosporin injections; Kilarski DJ et al.; The amount and size of particulate contamination in three commercially available cephalosporin injections and a new product, anophilized cephalothin sodium injection, were studied . Particles in reconstituted cephalothin sodium (commercially available and anophilized), cephapirin sodium, and cephradine injections were counted using two methods: (1) modified USP membrane-filtration technique and (2) Elzone computerized particle analyzer . The amount of particulate contamination in the ranges of 10-24 and greater than or equal to 25 microns was determined by both methods . In the 10-24-microns range, the cephalothin, cephapirin, and cephradine products had significantly greater particle counts than the anophilized cephalothin product . The greater than or equal to 25-microns particle counts showed that the cephapirin and cephradine products had particle counts greater than the anophilized cephalothin product, while total particle counts showed the same results as the 10-24-microns particle counts . A comparison of counting methods showed that the only significant difference between the number of particulates obtained using the modified USP and Elzone computer methods was with the cephalothin product . Anophilized cephalothin sodium injection has significantly fewer particles in the size ranges studied . No conclusion could be reached as to the more accurate method for counting particles.

Br J Surg, 1983 Apr, 70(4), 226 - 8
Two methods of skin closure in abdominal operations: a controlled clinical trial; Pickford IR et al.; Operative bacterial contamination of surgical wounds is common . The ability of the host to eradicate these bacteria and prevent subsequent wound infection is affected by a number of factors; one of these has been shown experimentally to be the presence of suture material in the subcutaneous tissues . In a prospective randomized controlled clinical trial in 341 abdominal operations we compared the primary infection rates after two methods of skin closure: either vertical mattress monofilament nylon sutures (182 patients) or steel clips which penetrated only the dermis (159 patients) . All patients received a single dose of a cephalosporin intravenously at induction of anaesthesia and neither sutures nor drains were placed in the subcutaneous plane . The overall wound infection rate in the sutured wounds was 17.0 per cent, compared with 6.3 per cent in those closed by clips (X2 = 9.26, P less than 0.01) . We conclude that skin closure with clips reduces the incidence of wound infection in patients in whom operative parietal contamination has occurred.

Hosp Formul, 1983 Apr, 18(4), 402 - 4, 407-8
Clinical pharmacist impact on parenteral cephalosporin prescribing; Lawlor MC et al.; A study was undertaken to evaluate clinical pharmacist influence on parenteral cephalosporin prescribing patterns . Two intervention methods were evaluated: (1) publication of pharmacy newsletter for physicians containing specific recommendations and emphasizing the primary use of cefazolin, and (2) personal interaction between the clinical pharmacy staff and physicians promoting the recommendations outlined in the newsletter . These two methods were compared with each other as well as with an initial time span during which no influencing efforts were made . The effect of the pharmacy newsletter as a sole means of influencing physician prescribing of parenteral cephalosporins was minimal . The effect of pharmacist-physician interaction, either as a sole means of in conjunction with a pharmacy newsletter, resulted in an increased use of cefazolin . An annual cost savings of up to $11,265.88 was projected . The results indicate that physicians can be influenced in their prescribing of parenteral cephalosporins, leading to significant cost savings.

J Pharmacol Exp Ther, 1983 Mar, 224(3), 520 - 4
Effects of piperonyl butoxide on cephalosporin nephrotoxicity in the rabbit . An effect on cephaloridine transport; Tune BM et al.; To evaluate the hypothesis that cytochrome P-450 mixed-function oxidase (MFO) activity may have a causal role in the production of cephalosporin nephrotoxicity, the effects of the MFO inhibitors cobaltous chloride and piperonyl butoxide on the nephrotoxicity of cephaloridine in the rabbit were examined . Although cobaltous chloride had no effect on cephaloridine nephrotoxicity, piperonyl butoxide had a significant protective effect . However, in correlated studies of the effects on the renal cortical uptake and disappearance of cephaloridine, it was found that piperonyl butoxide significantly reduces (by 50%) the cortical concentrations of the cephalosporin, both decreasing its uptake by and increasing its disappearance from tubular cells . Finally, we evaluated the effect of piperonyl butoxide on the nephrotoxicity of cephaloglycin, a more toxic cephalosporin that lacks the thiophene side-ring proposed as the target of MFO activation in earlier studies with cephaloridine . No protection against cephaloglycin was found . It is concluded that these inhibitors of MFO activity do not reduce cephalosporin nephrotoxicity in general, and that the reduction of cephaloridine toxicity by piperonyl butoxide can be explained by an effect on the intracellular concentrations of that particular cephalosporin.

Antimicrob Agents Chemother, 1983 Mar, 23(3), 413 - 5
Cefoperazone pharmacokinetics in preterm infants; Bosso JA et al.; The elimination pharmacokinetics of cefoperazone, a new cephalosporin, were studied in 15 preterm infants ranging in gestational age from 32 to 36 weeks and in postnatal age from 1 to 6 days . The infants received a single dose of either 50 or 250 mg of cefoperazone per kg by intravenous infusion . Blood samples were collected at specified times after completion of the drug infusion and then assayed for cefoperazone . Pharmacokinetic parameters were determined by noncompartmental analysis . Mean values for plasma half-life, elimination rate constant, apparent steady-state volume of distribution, and total body clearance were 5.53 h, 0.15 h-1, 124 ml/kg, and 36 ml/h per kg, respectively, for the group receiving a 50-mg/kg dose and 5.76 h, 0.14 h-1, 111 ml/kg, and 35 ml/h per kg, respectively, for the group receiving a 250-mg/kg dose . Positive correlations between gestational age and clearance and elimination rate were detected . A 50-mg/kg dose every 12 h ensured adequate serum levels for most of the common neonatal pathogens . Other than a transient rise in eosinophils in four subjects, no adverse effects were noted.

Biochem Pharmacol, 1983 Feb 15, 32(4), 621 - 6
Carrier-mediated transport of amino-cephalosporins by brush border membrane vesicles isolated from rat kidney cortex; Inui K et al.; The uptake of cephalosporin antibiotics by brush border membrane vesicles isolated from rat renal cortex has been studied by a rapid filtration technique, demonstrating a carrier-mediated transport system for amino-cephalosporins such as cephalexin and cephradine . The antibiotics were taken up into an osmotically reactive intravesicular space . The uptake of cephalexin was saturable (apparent Km2.2 mM), was inhibited by structural analogues and sulfhydryl reagents, and was stimulated by the countertransport effect, although the Na+ gradient did not affect the uptake . This transport system was essentially different from the transport system for p-aminohippurate in brush border membranes . The uptake properties for cephradine in brush border membrane vesicles appeared to be similar to those for cephalexin . The present results suggest the existence of a carrier-mediated transport system for amino-cephalosporins in brush border membranes . This system may be a part of the mechanism of tubular reabsorption of these antibiotics.

Wien Med Wochenschr, 1983 Jan 15, 133(1), 27 - 30
{Report of experiences with the oral cephalosporin-derivative cephaclor in respiratory tract infections}; Spath P; The oral cephalosporin derivative Cefaclor was administered to 22 patients with respiratory tract infections at a daily dosage of 3 x 500 mg . The average duration of the Cefaclor therapy was 10 days . In all patients improvement of the clinical picture and of objective criteria, such as fever, cough and sputum was observed . It was not possible to objectivate side effects by laboratory parameters . Gastrointestinal disturbances and allergic symptoms were only present in individual cases but did not significantly influence the clinical efficacy of Cefaclor.

J Foot Surg, 1983 Spring, 22(1), 66 - 8
Osteomyelitis of the foot; Marra R et al.; A favorable outcome was obtained in the case of an infected diabetic ulcer that resulted from neglect . The importance of appropriate antibiotic therapy and the advantage of a newer generation cephalosporin, cefamandole nafate (Mandol), is discussed . Optimal diagnostic information relative to the presence of osteomyelitis may be obtained by concomitant use of conventional radiographic technique and bone scanning . The most complete information concerning the status of diabetic control is gained by evaluation of standard blood glucose levels in conjunction with glycosylated hemoglobin A1C.

Antibiotiki, 1983 Jan, 28(1), 3 - 10
{Correlation of cephalosporin C synthesis and proteolytic enzymes in a differentiating culture of Acremonium chrysogenum (Cephalosporum acremonium) mutants}; Bartoshevich IuE et al.; The effect of the growth conditions and composition of the nutrient medium on the synthesis of cephalosporin C, alkaline exoproteases and cell differentiation was studied in various strains of Acremonium chrysogenum . It was observed that the changes in the above processes occurred simultaneously and depended on the aeration rate, temperature, illumination level and concentrations of methionine and soybean meal . Close correlation between the synthesis of alkaline exoproteases, cephalosporin C and formation of secondary structures in the strains of A . chrysogenum was shown.

Eur J Clin Pharmacol, 1983, 25(3), 407 - 12
Volume of distribution terms for a drug (ceftriaxone) exhibiting concentration-dependent protein binding . II . Physiological significance; McNamara PJ et al.; Guidelines presented previously for the analysis of plasma concentration versus time data for a drug exhibiting concentration-dependent plasma protein binding were successfully applied to the distributional parameters of a new cephalosporin, ceftriaxone . This approach provided several striking observations when the pharmacokinetics of ceftriaxone in a healthy and uremic population were re-examined . First, the parameter -fp converted the apparent dose-dependent distributional terms of ceftriaxone into a function of the concentration-dependent plasma protein binding . Second, a strong correlation between the term VUSS and the reciprocal of -fp was established within each of the two populations . While this -fp term accounted for the variability within the respective populations due to ceftriaxone-albumin binding differences, it did not account for all of the distributional differences between the two populations . The present analysis revealed that the altered physiologic state of uremia (larger plasma volumes and interstitial to intravascular albumin ratios), in addition to differences in plasma protein binding, dictated the distribution of ceftriaxone in healthy and uremic subjects . Furthermore, the binding-disposition model which accounts for the presence of plasma proteins outside the vascular space, was established to be appropriate in describing the distribution of ceftriaxone.

Chemotherapy, 1983, 29(3), 157 - 62
Absolute bioavailability of ceftriaxone after intramuscular administration to healthy volunteers; Delsignore R et al.; The disposition and bioavailability of ceftriaxone, a novel cephalosporin, was studied in 7 healthy volunteers after a single 1.5-gram intramuscular administration in comparison with the same dose given by the intravenous route . The plasma levels were measured by means of a high-performance liquid chromatography method up to 48 h after administration . Comparable areas under plasma concentration-time curve (AUC) and biological half-life were obtained proving that ceftriaxone, if assessed by conventional methods, is completely bioavailable when given by the intramuscular route . However, taking into account its nonlinear pharmacokinetics it becomes obvious that direct comparison of AUC values generally leads to a certain overestimation of bioavailability after extravascular administration . This aspect is briefly discussed.

J Pharm Sci, 1983 Jan, 72(1), 59 - 63
Kinetics and mechanism of degradation of cefotaxime sodium in aqueous solution; Berge SM et al.; The degradation kinetics and mechanism of a potent new cephalosporin, cefotaxime sodium, in aqueous solution were investigated at pH 0-10 at 25 degrees and an ionic strength of 0.5 . The degradation rates were determined by high-pressure liquid chromatography and were observed to follow pseudo first-order kinetics with respect to cefotaxime sodium concentration . The data suggested that the rate of degradation was influenced significantly by solvolytic, hydrogen ion, and hydroxide ion catalysis . No primary salt effects were observed in the acid or neutral regions; however, a positive salt effect was observed at pH 8.94 . Buffer catalysis due to the buffer species employed was not seen during the kinetic studies . The pH-rate profile at 25 degrees indicated that the maximum stability of cefotaxime sodium occurred in the pH 4.5-6.5 region . In aqueous solution, cefotaxime was shown to degrade by two parallel reactions: de-esterification at the C-3 position and beta-lactam cleavage . Good agreement between the theoretical pH-rate profile and the experimental data support the proposed degradation process.

Arch Orthop Trauma Surg, 1983, 101(4), 273 - 81
Moxalactam penetration of normal and osteomyelitic bone; Fitzgerald RH Jr; The ability of moxalactam, a new cephalosporin, to cross the capillary membrane and enter the interstitial fluid space of normal and osteomyelitic bone in the dog was investigated . Moxalactam was noted to readily traverse the capillary membrane of both normal and osteomyelitic bone . The calculated concentrations of moxalactam in the interstitial fluid space corresponded to the simultaneously obtained serum concentrations determined with a bioassay.

Int J Clin Pharmacol Res, 1983, 3(6), 459 - 74
Consequences of renal insufficiency on the hepatic clearance of some drugs; Balant LP et al.; There have been numerous investigations into the effect of kidney or liver diseases on the renal or hepatic elimination of drugs, but little is known about the possible consequences of renal insufficiency on the hepatic clearance of medicinal agents . The first reports of diminished presystemic elimination of drugs in renal failure were presented by Bianchetti in 1976 for propranolol and by Levy in 1979 for dextropropoxyphene . We confirmed the fact that the hepatic presystemic elimination of drugs might be diminished by kidney diseases . We studied this phenomenon with the beta-blocking agents tolamolol, bufuralol and oxprenolol . Tolamolol is eliminated from the body mainly by aromatic hydroxylation and, for bufuralol, aliphatic hydroxylation also plays an important role, whereas, for oxprenolol, glucuroconjugation of the unchanged compound is an important route of elimination . After oral administration, the areas under the plasma/blood concentration curves were markedly increased in patients with renal insufficiency as compared to healthy subjects . The clearance approach of Rowland and Tozer led to the conclusion that decrease of the presystemic hepatic elimination might be the main reason for this finding . Cefoperazone is a cephalosporin eliminated to 75% by the biliary route under normal conditions . In a study in which the drug was intravenously infused to both healthy volunteers and patients with renal insufficiency, we found that in some patients the extrarenal clearance was markedly reduced . It is probable that in this situation the patients also suffered from a slight hepatic insufficiency, as sometimes observed in the case of kidney disease associated with a poor physical condition . It is well-known that in patients with terminal liver failure, the kidney may also be involved, producing a condition known as the "hepato-renal" syndrome . We feel that there is evidence to support the hypothesis that renal failure can disturb the pharmacokinetics of drugs by processes other than merely reducing their renal excretion . The precise causes of the decreased hepatic elimination found in renal patients remains, however, to be determined.

Ann Osp Maria Vittoria Torino, 1983 Jan-Jun, 26(1-6), 91 - 6
{Clinical study of a new cephalosporin, ceftriaxone (Rocefin Roche) in bronchopneumonia in children}; De Marco A et al.; Ceftriaxone (Ro-13-9904) is a broad spectrum cephalosporin with a very long plasma half-life: about 8 h . We administered Ceftriaxone to 9 children suffering from bronchopneumonia . The clinical, X-ray and biochemical response were favourable in all cases.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1982 Dec, 253(3), 358 - 63
Purification and characterization of a cephalosporinase from E . coli; Seibert G et al.; The isolation and properties of a beta-lactamase from E . coli are described, which hydrolyses the Cephalosporins of the third generation . The enzyme has been brought to high purity by precipitation with (NH4)2SO4, gel chromatography and affinity chromatography on Cephalosporin C bound to agarose . The enzyme has been characterized by evaluation of its molecular weight 39 000, isoelectric point (pH 7.2), pH-optimum (pH 8.4) and substrate profile . It accepts Ceftizoxime, Cefamandole, Cefazolin and Cefotaxime as substrates, but shows nearly no activity on Penicillin G, Cefoxitin and the Desacetylmetabolite of Cefotaxime.

Antimicrob Agents Chemother, 1982 Dec, 22(6), 995 - 8
Simultaneous comparison of three methods for assessing ceftazidime penetration into extravascular fluid; Ryan DM et al.; The penetration of ceftazidime, a new broad-spectrum cephalosporin, into fluids from subcutaneous threads, suction blisters, and cantharidin blisters was studied in eight healthy male volunteers . A pharmacokinetic analysis showed fundamental differences between the models . The results obtained with the subcutaneous thread technique were similar to those of the peripheral compartment and were characteristic of a rapidly equilibrating compartment . The results obtained with the suction and cantharidin blister techniques were characteristic of slowly equilibrating compartments . We concluded that although one model will not accurately predict the penetration of an antibiotic in all clinical situations, each model will have its own particular application.

Sem Hop, 1982 Nov 11, 58(41), 2375 - 8
{4 cases of Mycoplasma pneumoniae pneumonia}; Vincent M et al.; The authors report four cases of Mycoplasma pneumoniae pneumonia which occurred towards the end of 1981, concurrently with an intensification of this infection . Three patients had severe respiratory distress and one required ventilatory assistance . The features shown on chest roentgenograms are discussed . All four patients had been treated initially with penicillin or cephalosporin . This report is evidence that patients with pneumonia should be given a macrolid as the first treatment.

Am J Hosp Pharm, 1982 Nov, 39(11), 1898 - 901
Influencing drug use through prescribing restrictions; Huber SL et al.; The effect of several drug restriction policies on benzodiazepine and cephalosporin use was evaluated in a large federal hospital . Computerized drug-use data were examined for the 10-year period from 1972 through 1981 . The five major types of drug restrictions implemented were the: (1) requirement that all diazepam prescriptions be countersigned by the chief of staff, (2) deletion of cephalothin sodium from the formulary, (3) required countersignature by a physician from the infectious disease service for all cefazolin sodium prescriptions, (4) requirement that justification accompany all cefazolin sodium prescriptions after the countersignature requirement was lifted, and (5) amendment of the countersignature requirement for diazepam with a series of designated exceptions . All of the restrictions resulted in a decrease in the number of dosage units dispensed; however, the required countersignature by the chief of staff and deletion from the formulary were the most effective in restricting drug use . The effect of the restriction policies appears to be related to the influence or power of the restriction enforcer and the perceived importance of the restriction, as well as the relative difficulty of drug acquisition by the prescriber . Formulary deletion, countersignature requirements, or restricted use to a service or physician are action plans that may alter the use rates of drugs.

J Antibiot (Tokyo), 1982 Oct, 35(10), 1351 - 60
Cephalosporin formation by cell-free extracts from Streptomyces clavuligerus; Jensen SE et al.; Cell-free extracts of Streptomyces clavuligerus convert delta-L-(alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV) into an antibiotic product which is 30 approximately 50% penicillinase-insensitive . Thin-layer chromatography resolves this antibiotic product into one major penicillinase-sensitive component and one major and one minor penicillinase-resistant component . The major and minor penicillinase-resistant antibiotics co-chromatograph with deacetoxycephalosporin C and deacetylcephalosporin C, respectively . Ring expansion of a penicillin intermediate, as evidenced by the production of penicillinase-resistant antibiotic, shows an absolute requirement for alpha-ketoglutarate, while ATP, K+ and Mg2+ have lesser effects . Ring expansion activity is not sedimented by high speed centrifugation and is unaffected by membrane-disrupting treatments . Penicillin N and ACV (presumably via penicillin N) are the only substrates so far accepted by the ring expanding enzyme . New syntheses of penicillin N and isopenicillin N are described.

Rev Infect Dis, 1982 Sep-Oct, 4 Suppl, S360 - 5
Pathogenesis of nephrotoxicity of cephalosporins and aminoglycosides: a review of current concepts; Silverblatt F; Third-generation cephalosporins promise to replace combinations containing aminoglycosides as safer, broad-spectrum antibiotic therapy . First, however, the possibility of nephrotoxicity as demonstrated with cephaloridine, must be excluded . For this reason, we must understand more about how cephalosporins and aminoglycosides damage the kidneys . Aminoglycosides accumulate in the renal lysosomes and may interfere with Na+-, K+-dependent adenosine triphosphatase activity . Experiments with cephaloridine and cephaloglycin, two nephrotoxic cephalosporins, indicate that they cause mitochondrial injury that leads to impaired cellular respiration . Results of experiments on the effects of treatments that combine cephalosporin with aminoglycosides or other drugs are confusing because inappropriate experimental models were used . Use of insensitive animals, administration of diuretics without prior induction of tubule damage, and insufficient dosages of drugs all cloud the interpretation of results . The standards for animal studies of cephalosporin nephrotoxicity should be revised to make them more relevant to humans.

Rev Infect Dis, 1982 Sep-Oct, 4 Suppl, S472 - 80
Cefotaxime therapy for patients with osteomyelitis and septic arthritis; Mader JT et al.; Cefotaxime, a new cephalosporin, was evaluated for efficacy and safety in the treatment of 52 patients with serious bone and joint infections . For five of these patients therapy could not be evaluated . Diagnosis of osteomyelitis or septic arthritis was made on the basis of clinical and roentgenographic evidence of infection . The diagnosis of a bone infection was confirmed by either a positive culture of a bone biopsy or of blood in combination with a positive bone scan or roentgenogram . The diagnosis of a joint infection was confirmed by a positive culture of joint aspirate samples . Osteomyelitis was arrested in 93% (15 of 16 patients) of cases of acute osteomyelitis, 89% (24 of 27 patients) of cases of chronic osteomyelitis, and 100% (4 of 4 patients) of cases of septic arthritis . Follow-up ranged from 0-17 months after completion of cefotaxime therapy . Laboratory monitoring revealed positive direct Coombs' test (six patients), neutropenia less than 1,000 polymorphonuclear leukocytes (two patients), macular rash (two patients), phlebitis (two patients), and pseudomembranous colitis (one patient) . It is concluded that cefotaxime is a useful and safe antibiotic for the treatment of osteomyelitis and septic arthritis.

Am J Hosp Pharm, 1982 Jul, 39(7), 1176 - 80
Use of clinical pharmacists to reduce cefamandole, cefoxitin, and ticarcillin costs; Abramowitz PW et al.; The financial impact of using cefamandole and cefoxitin rather than cefazolin and of using ticarcillin rather than carbenicillin in one institution was assessed; the effectiveness of clinical pharmacists in reducing the costs associated with these drugs also was determined . During Phase 1 (July 1, 1980-March 31, 1981), the numbers of intravenous piggyback cefazolin, cephalothin, cefamandole, cefoxitin, carbenicillin, and ticarcillin doses prepared were recorded . Quarterly purchase data for each drug were determined from invoice records . During Phase 2 (April 1, 1981-September 30, 1981), eight clinical pharmacists reviewed all patient charts for cefamandole, cefoxitin, and ticarcillin orders . If the indication for these orders was missing or considered inappropriate, the pharmacist contacted the prescriber and recommended substituting appropriate doses of cefazolin for cefamandole and cefoxitin and of carbenicillin for ticarcillin . The number of doses prepared and quarterly purchase data were collected as in Phase 1 . The projected savings resulting from clinical pharmacist input relating to these drugs was calculated . Based on Phase 1 data, the total theoretical expense resulting from cefamandole and cefoxitin use instead of cefazolin and from ticarcillin use in place of carbenicillin was projected to be $233,448 annually . Cefamandole and cefoxitin accounted for 59.8 and 39.7% of total cephalosporin use in Phases 1 and 2, respectively . Ticarcillin accounted for 77.1% of the total ticarcillin and carbenicillin doses in Phase 1, and 16.6% in Phase 2 . A projected annual savings of $156,756 was achieved because of clinical pharmacist input at a cost of $16,000 for time devoted to the effort . Clinical pharmacists were effective in reducing the use of cefamandole, cefoxitin, and ticarcillin in situations where cefazolin or carbenicillin could be substituted.

Jpn J Antibiot, 1982 Jul, 35(7), 1877 - 81
{Fundamental and clinical studies on cefotaxime in the perinatal period}; Yasuda J et al.; Fundamental and clinical studies on the perinatal use of cefotaxime (CTX, HR-756), a new cephalosporin antibiotic, were done, with the following results . 1 . Following intravenous administration of 2 g of CTX, transport of CTX from maternal serum to umbilical cord serum and to amniotic fluid was found to be good . CTX was not transferred into mother's milk . 2 . In clinical use, CTX was given to 16 pregnant patients with premature rupture of the membrane . It showed excellent efficacy in preventing perinatal infection . Five patients with perinatal infections were administered CTX, and in 4 patients CTX had good efficacy . No side effects were noted in any cases.

Jpn J Antibiot, 1982 Jul, 35(7), 1846 - 8
{Clinical studies of cefotaxime in perinatal infection}; Ishikawa M et al.; The therapeutic efficiency of a new cephalosporin derivative, cefotaxime, which is stable against beta-lactamase hydrolysis, has been studied in cases involving perinatal infection . The following results have been obtained . 1 . In the treatment of 7 cases of infection, the preparation showed excellent efficacy in 1 case and good efficacy in 5 cases except 1 unknown case . 2 . This drug has demonstrated its efficacy in the treatment of 5 cases of infections refractory to ABPC, out of which 1 had excellent and 3 had good results . 3 . No side effects were observed in any of our patients . In conclusion, this drug shows excellent efficacy and high safety in the treatment of cases involving infection.

Chir Ital, 1982 Jun, 34(3), 404 - 16
{Experience with cefoxitin in surgical sections of intensive care wards}; Mingolla F et al.; The Authors illustrate the results obtained in treatment of various types of infection in patients hospitalised in an intensive care surgical department with cephoxitin, a new semisynthetic antibiotic derivate of the cephalosporin group . In view of the severity of the treated cases, the Authors consider the results obtained to be satisfactory.

Antimicrob Agents Chemother, 1982 Jun, 21(6), 984 - 9
Comparison of the activities of ceftriaxone and penicillin G against experimentally induced syphilis in rabbits; Johnson RC et al.; The activity of ceftriaxone, a newly developed cephalosporin, against early cutaneous infections with Treponema pallidum in rabbits was compared with that of equimolar doses of penicillin G . Activity was related to the time required for cutaneous lesions to become dark-field negative, serological response, and the disappearance of T . pallidum from the popliteal lymph nodes . Both antibiotics were very effective in the treatment of syphilis in this animal model . The 50% curative dose for penicillin G was 0.8 mumol/kg (0.29 mg or 480 U/kg) and for ceftriaxone, it was 1.45 mumol/kg (0.96 mg/kg) . Overall, ceftriaxone was slightly less effective than penicillin G was . Transmission and scanning electron microscopy studies of testicular aspirates obtained from rabbits treated with ceftriaxone revealed alterations in the treponeme surface which apparently resulted in changes in cell permeability and morphology.

Arch Intern Med, 1982 May, 142(5), 1031 - 2
Exfoliative dermatitis during cefoxitin therapy; Kannangara DW et al.; An 84-year-old man was admitted to the hospital with a diabetic foot ulcer and osteomyelitis of the calcaneum . While being treated with cefoxitin sodium, he experienced generalized exfoliative dermatitis, which subsided on discontinuation of therapy . To our knowledge, this is the first report of exfoliative dermatitis with a cephalosporin or related drug.

Br Med J (Clin Res Ed), 1982 Apr 3, 284(6321), 1008 - 10
Short-term prophylaxis with cefotaxime for prostatic surgery; Hargreave TB et al.; A randomised controlled trial of a new cephalosporin, cefotaxime, was carried out in men undergoing transurethral resection of the prostate . The purpose of the trial was to determine whether 48-hour prophylaxis with this new broad-spectrum, non-nephrotoxic cephalosporin would reduce postoperative bacteriuria and postoperative complications . The treated patients fared significantly better than the non-treated patients in having fewer febrile episodes, fewer episodes of tachycardia, a lower incidence of appreciable bacteriuria postoperatively, and fewer complications, and spending on average one day less in hospital . There was no difference in postoperative urea and creatinine concentrations between the groups, and no other side effects of cefotaxime occurred in this elderly population . Prophylaxis with cefotaxime would appear to make prostatic surgery safer.

Appl Environ Microbiol, 1982 Apr, 43(4), 916 - 23
Changes in cell wall carbohydrate composition of Paecilomyces persicinus P-10 M1 during growth and cephalosporin C production; Malowitz R et al.; The carbohydrate composition of the cell walls of Paecilomyces persicinus P-10 M1 was monitored daily for 6 days to detect any changes during growth and cephalosporin C production . Walls were isolated after mechanical breakage, sonication, and exposure to detergent . Major quantitative changes in cell wall carbohydrate composition accompanied a decrease in both cell weight and antibiotic production . Glucosamine content remained relatively constant in the 24- to 96-h cell walls and increased markedly in the 120- and 144-h preparations . The non-nitrogenous carbohydrate cell wall component, however, decreased significantly in the 48- and 120-h cell walls . Gas-liquid chromatographic analysis of the non-nitrogenous carbohydrate cell well fraction revealed the presence of glucose, the major component, mannose, galactose, and minute quantities of arabinose . Except for glucose, which was found to decrease moderately in the 120- and 144-h cell walls, the neutral sugars did not vary significantly with time.

Antimicrob Agents Chemother, 1982 Apr, 21(4), 592 - 4
Minimal nephrotoxicity with cephalosporin-aminoglycoside combinations in patients with neoplastic disease; Brown AE et al.; Patients with cancer and suspected sepsis were treated in a prospective, randomized trial with one of four cephalosporin-aminoglycoside combinations: cephalothin and tobramycin; cephalothin and gentamicin; cefamandole and tobramycin; or cefamandole and gentamicin . Carbenicillin was added if the absolute granulocyte count was less than 1,000/mm3 . Of 199 patients receiving 20 to more doses of an aminoglycoside and having serial determination of serum creatinines, nephrotoxicity developed in seven (3.5%) given any of the four combinations . There were no significant differences between patients receiving either cephalosporin or either aminoglycoside . Nephrotoxicity developed less frequently among children (2 or 125; 1.6%) than adults (5 of 74; 6.8%).

J Infect Dis, 1982 Apr, 145(4), 574 - 81
Effects of ureteral obstruction on the toxicity of cephalosporins in the rabbit kidney; Wang PL et al.; The nephrotoxicity of the cephalosporin antibiotics is closely related to their secretory transport into the proximal tubular cell at the antiluminal (blood) site . The present report describes the effects of transient ureteral obstruction, which increases intracellular concentrations of secreted organic anions, on the cortical uptake and the proximal tubular toxicity of several cephalosporins given in mildly toxic doses . Unilateral obstruction for 1-2 hr increased the cytotoxicity of cephaloglycin and cefaclor, both of which are rapidly secreted across the tubular cell, but not of cephaloridine, which undergoes minimal secretion . Bilateral obstruction significantly increased the toxicity of cefaclor, which is rapidly secreted, but not of cefazolin, which is slowly secreted . Finally, there was a further augmentation of the effects of obstruction on the toxicity of cefaclor by a minimally toxic pretreatment regimen of neomycin . Studies of cortical antibiotic concentrations support the conclusion that the effects on toxicity are largely the result of the increased intracellular accumulation that results from obstruction.

Antimicrob Agents Chemother, 1982 Feb, 21(2), 323 - 6
Pharmacokinetics of ceforanide; Ripa S et al.; The pharmacokinetic of ceforanide, a new parenteral cephalosporin antibiotic, were examined at intravenous and intramuscular doses of 250, 500, and 1,000 mg in healthy male volunteers . Over the above dosing range, ceforanide pharmacokinetics were essentially linear, with plasma clearances varying from 2.2 to 2.5 liters/h . The best present overall estimate of the drug's half-life was 2.9 h . Intramuscular ceforanide was 100% bioavailable, Peak intravenous serum levels were 39, 71, and 135 micrograms/ml at the end of 30-min infusions of 250, 500, and 1,000 mg; after intramuscular injections of 250, 500, and 1,000 mg, the respective peak serum levels were 21, 38, and 69 micrograms/ml . From 80 to 85% of the above doses were eliminated as unchanged.

J Allergy Clin Immunol, 1982 Feb, 69(2), 238 - 44
Penicillin allergy: clinical experience with a battery of skin-test reagents; Solley GO et al.; From 1971 through August 1978, 778 patients underwent penicillin skin testing . Each patient gave a history of previous penicillin allergy . The skin-test reagents consisted of (1) fresh solutions of commercially prepared penicillin G (PEN G), ampicillin (AMP), and methicillin (METH); (2) polylysine conjugates of the major antigenic determinants of each of the three drugs: and (3) alkaline hydrolysates of each drug . A total of 108 (14%) patients showed positive reactions to one or more of the reagents . Certain patients showed reactivity to many reagents, whereas others reacted selectively to only one or two reagents . Addition of reagents of AMP and METH resulted in a greater number of positive reactors than when reagents of PEN G alone were used . Of the group whose skin tests were negative, 290 (43%) were later treated with penicillin, twelve of these (4.1%) had allergic reactions . Eight of the group of whose skin tests were positive were subsequently treated, and four of these (50%) had allergic reactions again . A group 151 patients whose skin tests were negative and 27 patients whose skin tests were positive were treated with a cephalosporin . Only two patients had allergic reactions to the drug: both had had negative skin tests to penicillin . We conclude that the risk of subsequent allergic reactivity to penicillin is much lower if the skin tests are negative than if positive, that testing with semisynthetic penicillins increases the number of skin-test reactors, and that the incidence of allergic reactions is low in patients treated with cephalosporin.

J Infect Dis, 1982 Feb, 145(2), 174 - 80
Prevention of cephalosporin nephrotoxicity by other cephalosporins and by penicillins without significant inhibition of renal cortical uptake; Tune BM et al.; Prevention of cephalosporin nephrotoxicity in animal models by probenecid or p-aminohippurate requires treatment regimen that produce sustained inhibition of cortical accumulation of the toxic antibiotic . In contrast, cephaloridine nephrotoxicity in the rabbit can be prevented by a limited single dose of cephalothin . In the present report further studies were done in which it was demonstrated that cephaloridine nephrotoxicity can be prevented by doses of other cephalosporins or penicillins that produce little or no reduction of the cortical concentrations of toxic cephalosporin . More limited studies revealed similar protection by benzylpenicillin against cephaloglycin, also without reduction of cortical concentration . Finally, similar limited-dose administration of penicillin eliminated tha additive toxicity of cefazolin and neomycin . This selective protection against the toxic cephalosporins by the less toxic or nontoxic cephalosporins and by the penicillins, without inhibition of overall cortical accumulation of the toxic antibiotic, may provide a subcellular probe for the study of the molecular basis of cephalosporin nephrotoxicity.

Mol Pharmacol, 1982 Jan, 21(1), 92 - 9
Study of the interaction between human serum albumin and some cephalosporins; Briand C et al.; Dialysis and microcalorimetric methods were used to calculate the binding parameters of some cephalosporins to human serum albumin (HSA) and to study the nature of the interactions involved in the binding process . Dialysis results agree with microcalorimetric data for cephapirin, cephradin, cefamandole, and cefazolin . Binding forces seem to be principally electrostatic . The parts of the drug molecule involved in HSA drug binding have been identified by high-resolution NMR . The major binding site for cephalosporins with high HSA affinity is thought to be the electron-rich heterocyle fixed on the methylene at position 3 . Four classes of cephalosporin have been defined: (a) very weak affinity for HSA (cephalexin, cephradin); (b) moderate affinity (cephapirin, cefoxitin, and cefotaxime) in which binding to the protein involves the heterocycle substituent of the acetamide chain carbon atom; (c) strongly binding (cefamandole), in which binding to HSA is by means of the methyltetrazole ring; and, finally (d), cefazolin, with two classes of binding sites for protein, showing strong and moderate affinity.

Chemotherapy, 1982, 28(3), 189 - 99
Biliary excretion of cefaclor . Experimental and clinical study; Brogard JM et al.; Biliary excretion of cefaclor, a new orally active cephalosporin, was studied in vitro using an isolated rabbit liver preparation perfused for 3 h (n = 5) . Under these conditions, bile recovery amounted to 2.3% of the cefaclor dose added to the circulating blood (10 mg) . In humans, after oral administration of a 1-gram dose of cefaclor to cholecystectomized patients provided with a T tube (n = 10), a mean biliary peak concentration of 7.6 +/- 2.4 microgram/ml was observed at the 3rd hour . Cumulative biliary excretion amounted to 0.05% of the administered dose . Assays performed on samples collected during cholecystectomy in 10 patients 1 h after intake of a 1-gram dose of cefaclor showed mean concentrations of 13.7 +- 1.2 micrograms/ml in serum, 8.1 +/- 1.3 micrograms/ml in common duct bile and 5.9 +/- 1.4 micrograms/ml in gallbladder bile . These results were compared with the data obtained after administration of seven other cephalosporins studied under identical conditions.

Chemotherapy, 1982, 28(5), 410 - 6
Treatment of experimental ascending Escherichia coli pyelonephritis with ceftriaxone alone and in combination with gentamicin; Glauser MP et al.; We have tested the effectiveness of several antibiotic regimens, using a rat model of Escherichia coli experimental pyelonephritis that mimics the conditions of severe renal infections in man because the infection is acquired by the ascending route . We found that ceftriaxone, when given for 5 days to rats with severe exudative pyelonephritis, was as effective as the combination ceftriaxone + gentamicin or the reference combination ampicillin + gentamicin . This effectiveness in vivo of the antibiotic alone was achieved despite a marked synergism between the combinations of antibiotics in vitro . This observation suggests that a new and extremely active cephalosporin is as effective in vivo when used alone as when given in combination with an aminoglucoside and provides rationale for testing the use of single antibiotic therapy for clinical situations for which combinations of antibiotics are currently recommended.

Antimicrob Agents Chemother, 1982 Jan, 21(1), 74 - 84
Regulation of cephamycin C synthesis, aspartokinase, dihydrodipicolinic acid synthetase, and homoserine dehydrogenase by aspartic acid family amino acids in Streptomyces clavuligerus; Mendelovitz S et al.; The effect of the cephalosporin precursors and amino acids of the aspartic acid family on antibiotic production by Streptomyces clavuligerus was investigated DL-meso-Diaminopimelate and L-lysine each stimulated specific antibiotic production by 75% . A fourfold increase in specific production was obtained by simultaneous addition of the two compounds . The stimulation could be further increased by adding valine to the two effectors . In the streptomycetes the alpha-aminoadipyl side chain of the cephalosporin antibiotics is derived from lysine . Streptomycetes, like other bacteria, are expected to produce lysine from aspartic acid; therefore, the feedback control mechanisms operating in the aspartic acid family pathway of S . clavuligerus, which may affect the flow of carbon to alpha-aminoadipic acid, were investigated . Threonine inhibited antibiotic production by 41% when added to minimal medium at a concentration of 10 mM . Simultaneous addition of 10 mM lysine completely reversed this inhibition . The aspartokinase of S . clavuligerus was found to be subject to concerted feedback inhibition by threonine and lysine . Threonine may act to limit the supply of lysine available for cephamycin C biosynthesis via this concerted mechanism . Single or simultaneous addition of any other amino acid of the aspartate family in the in vitro assay did not inhibit aspartokinase activity . Activity was stimulated by lysine . Aspartokinase biosynthesis was partially repressed by methionine or isoleucine at concentrations higher than 10 mM . Methionine, but not isoleucine, inhibited cephamycin C synthesis by 27% when added to minimal medium at a concentration of 10 mM . Dihydrodipicolinate synthetase, the first specific enzyme of the lysine branch, was not inhibited by lysine but was partially inhibited by high concentrations of 2,6-diaminopimelate and alpha-aminoadipate; it was slightly repressed by diaminopimelic acid . Homoserine dehydrogenase activity was inhibited by threonine and partially repressed by isoleucine . It appears that S . clavuligerus aspartokinase is a key step in the control of carbon flow toward alpha-aminoadipic acid.

J Med, 1982, 13(1-2), 121 - 30
Bleomycin compatibility with selected intravenous medications; Dorr RT et al.; Three separate in vitro admixture experiments were accomplished with bleomycin and other common parenteral medications . Bleomycin was assayed by a radioimmunoassay procedure . Bleomycin was found to be compatible with a majority of drugs including the aminoglycoside antibiotics, the vinca alkaloid antineoplastics, the antimetabolite fluorouracil, several phosphate salt corticosteroids, diphenhydramine and the anticoagulant heparin sulfate . Incompatible admixtures include the acidic cephalosporin and penicillin-derived antibiotics, the antineoplastics, methotrexate, and mitomycin C, the sodium succinate salt of hydrocortisone as well as ascorbic acid (vitamin C).

Jpn J Antibiot, 1981 Dec, 34(12), 1680 - 90
{Clinical evaluation of cefroxadine dry syrup in children (author's transl)}; Kobayashi Y et al.; Clinical efficacy of cefroxadine dry syrup, a new oral cephalosporin antibiotic, was evaluated in children, and the following results were obtained . 1 . Three children were given a single oral dose of about 10 mg/kg of the drug when fasting, and its blood concentrations were determined . Blood concentrations were maximum at 30 approximately 60 minutes, i.e., 16.9 approximately 18.2 microgram/ml, and markedly low at 4 hours . 2 . Thirty-six patients with the following diseases were tested with 23.1 approximately 44.4 mg/kg/day of the drug in 3 to 4 divided doses; 21 patients with lacunar tonsillitis, 2 with tonsillitis, 1 with scarlet fever, 4 with bronchitis and tonsillitis, 2 with cystitis, 4 with pyelonephritis, 1 with impetigo and 1 with probable Mycoplasma pneumonia . An overall efficacy rate in 35 patients excluding the last mentioned case was 91.4%, i.e., excellent in 20, good in 12 and poor in 3, and an eradication rate of the causative organisms was 88.9% . 3 . Adverse reactions noted were diarrhea in 1 patient, eruption and diarrhea in 1 transient neutropenia in 1, eosinophilia in 3 and an elevation of GOT and GPT in 1 . None were significant . 4 . Taste and flavor of the drug was considered to be well palatable to children . 5 . Taking into consideration of the results of fundamental evaluation of the drug, cefroxadine dry syrup is considered to be a potent new antibiotic in children, and the recommended dose will be 10 mg/kg 3 to 4 times a day.

Am J Hosp Pharm, 1981 Dec, 38(12), 1897 - 900
Cost containment through restriction of cephalosporins; Britton HL et al.; The effect of a program designed to reduce hospital drug costs by limiting the selection of injectable cephalosporins and promoting the rational use of the selected agents was studied . Cefazolin sodium was chosen as the primary injectable cephalosporin, and guidelines for proper dosing were approved . Strict guidelines for the use of cephapirin sodium, cefamandole nafate, and cefoxitin sodium were also adopted; cephalothin sodium was deleted from the formulary . Clinical pharmacists reviewed all cephalosporin orders and consulted with prescribers whose orders did not conform to the guidelines . Total cephalosporin purchases for the first fiscal year of the program were $64,914, a decrease of $55,715 or 46.2% from the previous year's total of $120,629 . Cost per patient day for cephalosporins decreased from $0.921 to $0.519 (43.6%) over the same period . The number of milligrams of cephalosporins used per patient day decreased from 398.16 to 178.77 (55.1%), while the number of patient days decreased by only 4.45% during the same interval . The estimated annual cost of monitoring the program was $1500 . This program demonstrates that substantial cost savings can be achieved if guidelines for the use of injectable cephalosporins are clearly outlined and strictly enforced.

J Pharm Sci, 1981 Oct, 70(10), 1120 - 8
Degradation kinetics and mechanism of aminocephalosporins in aqueous solution: cefadroxil; Tsuji A et al.; The degradation kinetics and mechanism of a new, orally effective cephalosporin derivative, cefadroxil, in aqueous solution were investigated at pH 2.51-11.5 at 35 degrees and ionic strength 0.5 . The degradation rates were determined by high=pressure liquid chromatography . At constant pH and temperature, the degradation followed first-order kinetics and a log k-pH profile was presented . The shape of the rate-pH profile resembled that for cephalexin or cephradine under the same conditions . Citrate and phosphate buffers enhanced general acid and base catalysis of the degradation . In aqueous solution, cefadroxil was shown to degrade by three parallel reactions: (a) intramolecular aminolysis by the C-7 side-chain amino group on the beta-lactam moiety, (b) water-catalyzed or spontaneous hydrolysis, and (c) beta-lactam cleavage by the nucleophilic attack of hydroxide ion . In neutral and weak alkaline solutions, the main degradation products were two piperazine-2, 5-diones and 3-hydroxy-4-methyl-2(5H)-thiophenone, the former being formed from Reaction a, while the latter arose via the degradation pathways of Reaction b and/or c.

Chest, 1981 Sep, 80(3), 259 - 63
Organizing pneumonia-like process: an unusual observation in steroid responsive cases with features of chronic interstitial pneumonia; Grinblat J et al.; Two patients under long-term surveillance showed the similar clinical features of low-grade fever, scanty productive cough, progressive dyspnea, and roentgenologic findings of lung infiltrates . Both patients responded only to systemic corticosteroid therapy and suffered relapses when it was discontinued . In one patient, who was found to be IgA-deficient, the pulmonary disease followed an episode of subacute thyroiditis; in this patient the intake of cephalosporin and subsequent rechallenge with the drug aggravated the disease . Needle biopsies in both patients showed the features of organizing intra-alveolar pneumonia . The histopathologic findings and their relation to the clinical symptoms are discussed.

J Antibiot (Tokyo), 1981 Aug, 34(8), 984 - 93
High performance liquid chromatography (HPLC) of natural products . IV . The use of HPLC in biosynthetic studies of cephalosporin C in the cell-free system; Miller RD et al.; A new cepham metabolite has been isolated from the filtered broth of Cephalosporium acremonium by high performance liquid chromatography (HPLC) and identified as 7 beta-(5-D-amino-adipamido)-3 beta-hydroxy-3 alpha-methyl-cepham-4 alpha-carboxylic acid (I) . Pure penicillin N was prepared using HPLC in the analytical mode . When I was added in place of penicillin N as substrate for the cell-free biosynthetic of cephalosporin, no formation of deacetoxycephalosporin C (II) was observed . A synthetic cepham derivative, 7 beta-(5-D-aminoadipamido)-3-exomethylene-cepham-4 alpha-carboxylic acid (III) was also tested in the cell-free system as a possible intermediate . The compound III was shown to be an inhibitor of the ring expansion enzyme that converts penicillin N to deacetoxycephalosporin C.

Am J Physiol, 1981 Jul, 241(1), F1 - 8
Nephrotoxic acute renal failure due to common drugs; Porter GA et al.; Antibiotics are the most common drugs implicated in clinical reports of drug-induced nephrotoxicity . The experimental basis for proposed mechanisms of acute renal failure in association with three groups of antibiotics--aminoglycoside, cephalosporin, and amphotericin B--are reviewed in detail . Proposed mechanisms of antibiotic-induced acute renal tubular necrosis involve either altering plasma membrane permeability or interference with cellular energy derived from mitochondria, For either aminoglycoside or cephalosporin antibiotics, cellular accumulation followed by interruption of mitochondrial respiration is the concept that has greatest support, although the possibility of an induced phospholipidosis involving intracellular lysosomes cannot be excluded . Altered renal tubular cell permeability due to the incorporation of amphotericin B into the pore structure of the plasma membrane is consistent with in vivo observation in either clinical or experimental examples of nephrotoxicity with this agent . The metal cis-platinum, used in treatment of neoplastic disease, has a clearly defined incidence of clinical nephrotoxicity with little insight as to cellular mechanisms . A possible mediation involving cis-platinum reducing the protein-bound sulfhydryl group of renal tissue has been proposed . With the ever increasing potency of modern pharmacologic agents come a rising risk of serious toxic side effects.

Zhonghua Min Guo Wei Sheng Wu Ji Mian Yi Xue Za Zhi, 1981 Jun, 14(2), 73 - 7
{Trichomonas hominis: isolation and axenic cultivation (author's transl)}; Shaio MF et al.; Recently we have isolated Trichomonas hominis from diarrheic stools of a patient and established it in an axenic culture medium . The procedures are as follows: Diarrheic stool containing numerous trophozoites was first inoculated into the TYM (Trypticase Yeast extract Maltose) medium of Diamond (1975) to establish a polyxenic culture . Antibiotics, containing penicillin (1000 U/ml), streptomycin (1000 micrograms/ml), and cephalosporin (20 micrograms/ml) were added to prevent overgrowth of bacteria and fungi . After several passages, a specially-designed culture-tube was employed to separate T . hominis from the contaminants . The isolated T . hominis was then introduced into the modified TYI-S-33 (Trypticase Yeast extract Iron-Serum-33) medium of Diamond (1978) . The organism established itself readily to this axenic culture medium . Sterility tests employing fluid thioglycollate, nutrient broth, and blood agar plate gave negative results indicating the absence of contaminants . The axenic culture of T . hominis provides us with a source of pure flagellates for biological, biochemical, and immunological studies.

Clin Pharmacol Ther, 1981 May, 29(5), 650 - 7
Effects of concentration-dependent plasma protein binding on ceftriaxone kinetics; Stoeckel K et al.; The kinetics of ceftriaxone, a cephalosporin, was studied in six healthy subjects who received bolus injections of 150, 500, and 1,500 mg intravenously in a random crossover fashion . Although total drug concentration time profiles after all doses could be described by biexponential equation, simple compartment analysis was inappropriate because a disproportional increase in the area under the total drug concentration time curves occurred with dose . This resulted in a dose-dependent increase in total systemic clearance (ClTS) from 9.7 ml/min at the 150-mg dose to 13 ml/min at the 1500-mg dose . The dose-dependent changes in ClTS could be explained in terms of the concentration-dependent plasma protein binding of ceftriaxone (fplasma ranging from 0.04 to 0.167), because the area under the free drug concentration time curves (AUCFO-infinity) increased proportionately to dose . Mean total clearance with reference to free (unbound) ceftriaxone (ClFS) was constant at 255 ml/min . Calculated mean renal clearance with reference to free ceftriaxone (ClFR) was 173 ml/min, or slightly more than the average glomerular filtration rate in humans . Mean plasma ceftriaxone t1/2 was not influenced by dose and averaged 8 hr . This biological t1/2 is by far the longest ever for a cephalosporin in healthy subjects.

Minerva Med, 1981 Apr 2, 72(13), 813 - 8
{Clinical study on a new cephalosporin: CGP 9000 (cefroxadine)}; Soranzo ML et al.; CGP 9000 (cefroxadine), a new cephalosporine derived from N-acyl-3-alkoxy-7-amino-3-cefem-4-carboxylic acid for exclusively oral use, has been experimented on 67 patients, 41 adults and 20 children . CGP 9000 appeared to possess good therapeutic activity, even in low doses: its rapid absorption and moderate sero-protein bond are a guarantee of an immediate and almost total bioavailability.

Am J Hosp Pharm, 1981 Apr, 38(4), 513 - 7
Restricted cephalosporin use in teaching hospitals; Johnson PN et al.; The approaches of teaching hospitals toward limiting the number of cephalosporin drug products on formularies were studied in a mail survey . Pharmacy department directors of 128 teaching hospitals with 200 beds or more responded to teh survey . Forty-two of 128 (33%) hospitals had established formal restriction policies (FRPs) for cephalosporins (CS) . Cephalexin and cephradine were the predominant formulary oral CS . Few hospitals had established "therapeutic equivalents" policies, yet the majority of hospitals had a single oral CS on the formulary . Cefazolin was the predominant injectable CS on all formularies; cefamandole and cefoxitin were the predominant restricted CS . In hospitals without restriction policies, these newer CS were on the formulary in 55% of the cases; in FRP hospitals, the figure was 15% . The occurrence of a single, formulary, unrestricted CS was much more likely in FRP hospitals (38%) than in hospitals with no restriction policy (NRP) (8%) . FRP hospitals tended to have fewer unrestricted formulary CS . Eighty-three percent of FRP hospitals and 41% of NRP hospitals monitored CS use.

Br J Surg, 1981 Apr, 68(4), 290 - 1
The excretion of cefuroxime in human bile; Thomas MH et al.; Cefuroxime is a broad spectrum cephalosporin antibiotic . An intravenous injection of cefuroxime 1.5 g was administered to 25 patients after induction of anaesthesia for cholecystectomy . Concentrations of antibiotic were measured and the mean levels in microgram/ml found to be: serum 120.5, common bile duct bile 42.8, gallbladder bile 5.4, gallbladder wall 39.2 . The drug levels exceeded the minimum inhibitory concentrations for most organisms commonly encountered in the biliary tract . There was no difference in cefuroxime levels in bile from functioning or non-functioning gallbladders . It is suggested that the diffusion of antibiotic into and out of the inflamed gallbladder is similar to that in abscesses and in experimental tissue cages . No side effects, toxicity or wound infections occurred.

Jpn J Antibiot, 1981 Apr, 34(4), 537 - 44
{Laboratory and clinical studies on cefotaxime in obstetrics and gynecology (author's transl)}; Ishii Y et al.; We have conducted basic and clinical examination of a new cephalosporin derivative, cefotaxime (CTX) . The average level of transfer measured at various locations in uterus tissue and adnexa 15 to 105 minutes (53.4 minutes in average) after intravenous administration of this drug ranged from 1.5 mcg/g (myometrium) to 3.3 mcg/g (portio vaginalis) . It was distributed in cervix uteri and portio vaginalis at highest concentration, followed by oviduct, tunica serosa and ovary, and to myometrium at lowest concentration . The same pattern of distribution was observed in transfer ratio of various location in uterus tissue to uterus arterial blood . The drug was transferred at very high level in pelvic cavity fluid after total hysterectomy throughout 3 postoperative hours . Five cases of gynecological infections receiving in total 10 to 42 g of CTX demonstrated 'excellent' results in 2 cases, and 'good' in 3 cases . Out of these, 3 cases did not respond to other antibiotic . Neither side effect nor clinical test abnormality was observed, except for one case, in which mild increase of GOT and GPT occurred . Based on the results of basic and clinical studies as described above, this drug is considered to have excellent efficacy and safety.

Jpn J Antibiot, 1981 Apr, 34(4), 515 - 20
{Fundamental and clinical studies on cefotaxime in the field of obstetrics and gynecology (author's transl)}; Kanao M et al.; Fundamental and clinical studies were made on cefotaxime (HR-756, CTX), a new cephalosporin antibiotic, with the following results . 1 . Cefotaxime was given to 22 patients . Efficacy was excellent in 3 cases, good in 17 cases and poor in 2 cases . No side effects were observed in any cases . 2 . Following a single intravenous injection of 1.0 or 2.0 g, the transfer of CTX to the internal genital organs was found to be good . The transfer of CTX to exudate of the dead space of pelvis was also good . 3 . The above data demonstrated that CTX is a safe and effective drug.

Antibiotiki, 1981 Mar, 26(3), 83 - 8
{Regulation of alkaline exoprotease and cephalosporin C synthesis in Acremonium chrysogenum by different carbon and nitrogen sources}; Shuvalova IA et al.; The synthesis of exoproteases and cephalosporin C in Acremonium chrysogenum is repressed by easily assimilated forms of nitrogen and carbon according to the type of nitrogen metabolism repression and catabolism inhibition . Glucose and ammonium salts inhibited the mycelium fragmentation and prevented formation of conidia . Amino acids had a diverse effect on the synthesis of the proteases and antibiotic . Methionine played the role of an inductor of the synthesis of alkaline exoproteases, cephalosporin C and the mycelium fragmentation into arthrospores.

Jpn J Antibiot, 1981 Mar, 34(3), 404 - 11
{Clinical study on ceftezole in oral surgery . Clinical effect of ceftezole used jointly with gamma-globulin (Gamma-Venin) (author's transl)}; Ishikawa M et al.; Ceftezole, an antibiotic of cephalosporin C derivative was applied to treatment in 39 patients with odontogenic inflammation or postoperative infections . The drug was administered intravenously (1-5 g/day) for the period of 5-10 days . Twenty of them were administered jointly with gamma-globulin (Gamma-Venin) . Therefore, we compared clinically between the group of ceftezole with Gamma-Venin and the other group without it . But no difference was noticed statistically between these groups . No side effect was observed with throughout all the cases.

Nouv Presse Med, 1981 Feb 26, 10(8), 585 - 6
{Comparative study of cefotaxime serum and lung concentrations in 6 patients with thoracotomy (author's transl)}; Pous J et al.; This study was performed on samples obtained from 6 patients undergoing pulmonary surgery . Cefotaxime was administered by the i.m . route at a dose of 1 g twice daily and assays were performed on simultaneously obtained lung biopsies and serum . The comparison of tissue levels to the peak serum concentrations obtained at 30 minutes after injection provided evidence of the excellent tissue penetration of this cephalosporin in the human lungs.

Chemotherapy, 1981, 27 Suppl 1, 42 - 6
Pharmacokinetics of Rocephin, a highly active new cephalosporin with an exceptionally long biological half-life; Stoeckel K; The total (bound and unbound) plasma concentration time profiles following the three intravenous doses of Rocephin (150, 500 and 1,500 mg) declined in a biphasic manner . A simple compartment analysis was inappropriate since a dose-disproportional increase in the area under the total drug concentration time curve (AUCT,0(-8)) occurred . This resulted in unstable, dose-dependent total systemic clearance (9.7-13.0 ml/min) and volume of distribution (7.0-8.6 litres) values . The dose-dependent pharmacokinetic changes could be completely explained in terms of the concentration-dependent plasma protein binding (fp ranging from 0.04 to 0.17 in the concentration range from 0.5 to 300 micrograms/ml) . Hence, the pharmacokinetics of free (unbound) Rocephin was linear and dose-independent . With reference to free (unbound) drug the mean total clearance was 255 ml/min and the mean renal clearance about 160 ml/min . The renal clearance was therewith slightly higher than the average glomerular filtration rate in man (approximately 125 ml/min) . Consequently the coadministration of probenecid (1 g) had no effect on the pharmacokinetics of Rocephin . The mean plasma half-life of Rocephin was not influenced by dose and averaged 8 h . It was therewith the longest ever reported one for a cephalosporin in healthy volunteers.

Arzneimittelforschung, 1981, 31(7), 1163 - 5
Controlled assessment of the concentrations of a new cephalosporin in bile and gallbladder; Vittorini C et al.; The distribution of cephalexin in bile and in the gall bladder was investigated in humans after administering pivalexin--a new cephalexin derivative--that exhibits favourable pharmacokinetic characteristics versus cephalexin itself . Two groups of subjects were given either pivalexin or cephalexin in the form of capsules in a single oral dose . Pivalexin in view of its greater excretion of cephalexin in bile and its satisfactory fixation of cephalexin in the gallbladder, as compared with cephalexin itself, may reasonably be regarded as a recommendable antibiotic in the treatment of biliary-duct infections.

Curr Med Res Opin, 1981, 7(3), 168 - 70
A pharmacological study of cefaclor in the newborn infant; Chin KC et al.; The absorption and excretion of cefaclor were studied in 10 newborn infants . A mean peak serum concentration of 7.7 microgram/ml was achieved at 1 hour after an oral dose of 7.5 mg/kg . It is concluded that cefaclor is a well absorbed and tolerated cephalosporin for use in newborn infants.

J Bacteriol, 1981 Jan, 145(1), 398 - 403
Purification of penicillin-binding protein 2 of Escherichia coli; Curtis SJ et al.; Penicillin-binding protein 2 (PBP-2) of Escherichia coli K-12 was purified by covalent affinity chromatography using 6-aminopenicillanic acid covalently coupled to carboxymethyl-Sepharose (6-APA-CM-Sepharose) . Purification of PBP-2 was accomplished by prebinding the methoxy cephalosporin, cefoxitin, to the Triton X-100-solubilized PBPs of E . coli and then incubating the PBPs with 6-APA-CM-Sepharose . Cefoxitin readily binds to all the E . coli PBPs except PBP-2 and, thus, in the presence of cefoxitin, only PBP-2 could bind to the 6-APA-CM-Sepharose . The purification of a mixture of all of the PBPs of E . coli by affinity chromatography is also described.

Arzneimittelforschung, 1981, 31(10), 1770 - 2
{Concentration of cefoperazone in various tissues of the urogenital system (author's transl)}; Schalkhauser K et al.; Within the framework of perioperative short-term prophylaxis against infections, serum and tissue concentrations were investigated after a single i.v . bolus injection of 2.0 g cefoperazone (Cefobis), a semisynthetic cephalosporin parenterally applicable, in 30 patients with a prostatic adenoma . The mean serum concentrations ranged from 82.0 micrograms/ml at 30 min to 41.9 micrograms/ml at 150 min following the injection decreasing continuously . The corresponding mean concentrations in the tissue of prostatic adenoma were 17.8 micrograms/g and 13.9 micrograms/g, the maximum concentrations were found 90 min after the injection with 21.6 micrograms/g . Most differing concentrations were found in 14 kidneys 90 min after injection . The individual values varied between 5.5 micrograms/g and 70.2 micrograms/g . These ranges of variation must be attributed to the differing clinical and histological diagnoses of the collected organs with highly differing degrees of function . Effective levels of 7.0 micrograms/g to 28.9 micrograms/g were found at different times in 13 testes of 14 patients undergoing plastic orchidectomy because of a carcinoma of the prostata . Average concentrations of 10.3 micrograms/g to 13.2 micrograms/g in the ureter, adipose tissue and muscle were within the therapeutically effective range . The high cefoperazone concentrations found in serum and different tissues lead us to expect successful therapy when cefoperazone is used to treat bacterial infections with sensitive pathogens in the urogenital tract.

J Antibiot (Tokyo), 1981 Jan, 34(1), 84 - 9
IgE antibodies for penicillins and cephalosporins in rats . III . Antigenic specificity of rat anti-cephalosporin-OvA IgE sera; Shiho O et al.; Sprague Dawley (SD) rats were immunized with various cephalosporin- and penicillin-ovalbumin (OvA) in combination with aluminium hydroxide (alum) and thimerosal-killed Bordetella pertussis . Anti-cephalosporin IgE antibody production was inferior to anti-penicillin IgE antibody production . Cefsulodin (CFS), sulbenicillin (SBPC) and alpha-sulfophenyl acetic acid (SPAA) cross-reacted with each other but did not react with cephaloridine (CER), cefazolin (CEZ) and penicillin G (PCG) . CER and PCG slightly cross-reacted with each other but did not cross-react with the others tested . Anti-CFS and anti-SBPC IgE sera were related specifically to the SPAA moiety.

Jpn J Antibiot, 1980 Dec, 33(12), 1277 - 84
{Fundamental and clinical studies of cefuroxime in pediatric purulent meningitis (author's transl)}; Toyonaga Y et al.; The following results were obtained from the fundamental and clinical studies of cefuroxime, a new synthetic cephalosporin, in pediatric patients with purulent meningitis . This drug was administered to 2 pediatric patients with purulent meningitis at the dose to 50 mg/kg, by intravenous drip infusion over 30 minutes and one shot intravenous injection respectively . When spinal fluid levels were determined, about 15 approximately 30% of the drug concentration in blood was found to transfer to spinal fluid at acute stage . Spinal fluid levels were about 4 approximately 7 micrograms/ml . When 4 pediatric patients with purulent meningitis were treated with the drug, the good results were obtained in all of them . The dose given was 200 approximately 300 mg/kg/day and the dosing duration was 14 approximately 22 days . No adverse reaction was noted, nor abnormal laboratory test values were noted.

Jpn J Antibiot, 1980 Dec, 33(12), 1306 - 12
{Clinical studies of cefoperazone in the treatment of pyoderma (author's transl)}; Gondo A et al.; Cefoperazone (CPZ), a new semisynthetic cephalosporin derivative, was administered in the treatment of pyoderma . The results are shown as follows . CPZ was given to 21 patients with pyoderma . In 21 patients, marked improvement was seen in 7, effectiveness in 10, slight improvement in 1 and ineffective in 3 . Total clinical effectiveness rate was 81.0% . No serious side effects were observed.

Arch Microbiol, 1980 Nov, 128(1), 78 - 83
Regulation of cephalosporin synthesis in Cephalosporium acremonium by phosphate and glucose; Kuenzi M; The regulation of cephalosporin synthesis in Cephalosporium acremonium was studied in a simple chemically-defined medium with glucose as the carbon source . Antibiotic synthesis depended on the phosphate content of the medium . At phosphate concentrations above 2.75 mM maximum antibiotic titres were not reached while glucose uptake and growth rates were increased . Phosphate exerted its effect indirectly by regulating the rate of glucose consumption . The negative effect of high phosphate concentrations could be overcome completely by controlling the sugar supply in fed-batch and chemostat experiments . High actual concentrations of phosphate or of glucose alone had no direct negative effect on antibiotic synthesis.

J Pharmacol Exp Ther, 1980 Oct, 215(1), 186 - 90
Cephalosporin nephrotoxicity . Transport, cytotoxicity and mitochondrial toxicity of cephaloglycin; Tune BM et al.; The cephalosporin antibiotics are secreted by the renal organic anion transport system . Several of them, including cephaloridine and caphaloglycin, produce a proximal renal tubular necrosis which can be prevented by inhibitors of organic anion transport . Although cephaloridine is actively transported into the tubular cell at the antiluminal side like other cephalosporins, it undergoes a limited rate of subsequent movement across the luminal membrane into the tubular fluid . The very high intracellular concentrations that result from this unusual process are believed to contribute to the significant toxicity of cephaloridine . Cephaloglycin is at least as toxic, but is secreted more normally across the proximal tubular cell . For this reason, studies were undertaken to evaluate the cytotoxicity, cortical concentrations and mitochondrial respiratory toxicity of this cephalosporin in the rabbit kidney . A dose of 100 mg/kg of caphaloglycin produces as much damage as does 150 mg/kg of cephaloridine . The steady-state cortex-to-serum concentration ratio of cephaloglycin, 5.6 +/- 0.8 S.E . (n = 5), is significantly lower (P < .001) than the corresponding measurement for cephaloridine, 121.9 +/- 1.2 (n = 7), and is not significantly different from that of p-aminohippurate . In further contrast to cephaloridine, the cortical concentration of cephaloglycin declines substantially, from 930 +/- 112 (n = 5) to 297 +/- 46 (n = 5) micrograms/g of wet tissue, over the first hour after cessation of infusion (P < .001) and is essentially unmeasurable by 2 hr . The fact that there is not the prolonged intracellular trapping of cephaloglycin that is seen with cephaloridine leads to the conclusion that the former must either bind more strongly to its target receptor or produce a more irreversible insult than does the latter cephalosporin . Several lines of evidence are presented which support this hypothesis . The most important of these are that cephaloglycin is cumulatively nephrotoxic, whereas cephaloridine is not, and that the in vivo toxicity of cephaloglycin to cortical mitochondria, unlike that of cephaloridine, is not significantly diminished by the mitochondrial isolation process . This very early in vivo respiratory toxicity of cephaloglycin and the lack of significant similar toxicity of cephalexin provide new evidence that the effect on mitochondria may have a pathogenic role in cephalosporin nephrotoxicity.

Jpn J Antibiot, 1980 Oct, 33(10), 1056 - 83
{Subacute toxicity test of cefoperazone in beagle dogs with the intramuscular administration for 3 months (author's transl)}; Yoneda T et al.; The subacute toxicity test of cefoperazone (CPZ), a new cephalosporin antibiotic, was carried out in both sexes of Beagle dogs . CPZ was injected in Beagle dogs intramuscularly at dose levels of 500, 250 and 125 mg/kg/day for 3 months . The same amount of physiological saline was injected to control dogs intramuscularly for 3 months . The following results were obtained: 1) Sign of severe pain was shown immediately after injection in groups of CPZ at 500 and 250 mg/kg/day . In the same groups, the focal necrosis, hemorrhage, cell infiltration and fibrosis of muscles of injected site were noted microscopically . 2) In only one out of 6 dogs given CPZ at 500 mg/kg/day for 3 months, decrease of red blood cells and in values of hemoglobin and hematocrit an increase of reticulocytes in the peripheral blood were observed . In the same dog, splenomegaly and extramedullary hematopoiesis in the liver was found histopathologically, and in addition, the body weight and the food intake decreased during the administration period, associated with the development of anemia . 3) In dogs receiving up to 250 mg/kg/day, atrophy of the thymus was recognized at autopsy and slight decrease of cortical lymphocytes was seen histopathologically . 4) Based on these results, the maximum safety dose of CPZ was thought to be 125 mg/kg/day from the present experiment.

Res Commun Chem Pathol Pharmacol, 1980 Sep, 29(3), 429 - 44
Antagonism by classical antiepileptics and sodium valproate of cefazolin in induced experimental epilepsy in rats; Nistico G et al.; The effects of cefazolin, a semisynthetic cephalosporin, on rat behavior, electrocortical activity and on electrocortical spectrum power were evaluated . In addition, the possible antagonism by some antiepileptic agents was studied . Cegazolin, given intravenously in rats, produced generalized convulsions, electrocortical high-voltage spikes and other electrocortical abnormalities similar to those described to occur in human epilepsy . Power spectrum analysis of the electrocortical activity revealed a significant increase in total voltage output during electrocortical epileptogenic discharges . In addition high-voltage spikes induced by cefazolin were easily counted and lasted approximately 90 min . Classical antiepileptic drugs (diphenylhydantoin, phenobarbital and clonazepam as well as sodium valproate were able to counteract electroclinical disorders induced by cefazolin.

Jpn J Antibiot, 1980 Sep, 33(9), 935 - 40
{Clinical examination of cefoperazone in pediatrics (author's transl)}; Matsuda H et al.; Clinical studies on cefoperazone (CPZ), a new cephalosporin, were carried out at our department . Seventeen children wih the following bacterial infections were treated with CPZ; pneumonia (7), bronchitis (6), tonsillitis (1), sepsis (2) and purulent meningitis (1) . The dosage was 56 approximately 182 mg/kg/day, divided into 4 doses, and given intravenous injection . The duration of administration was from 4 to 15 days . Clinical results were excellent in 3 cases, good in 9 cases, moderate in 3 cases, poor in 1 case and uncertain in 1 case . The overall efficacy rate was 75.0% . No side effects were observed.

Jpn J Antibiot, 1980 Sep, 33(9), 891 - 8
{Fundamental and clinical studies of cefoperazone in pediatric patients (author's transl)}; Kamiya H et al.; 1 . Susceptibility, concentrations in serum and spinal fluid, and clinical effect of cefoperazone (CPZ), a newly developed cephalosporin in Japan, were examined in 28 infants from 2 days to 12 years of ages with various infections . 2 . The overall clinical evaluation in 22 cases received CPZ alone was found to be markedly effective in 11 cases and effective in 6 cases; the efficacy rate was as good as 85.0% . 3 . The mean half-life following a single intravenous injection of 25 mg/kg to 3 infants was 80.7 minutes . 4 . The side effects observed during the therapy were 2 cases of rash and 1 case of vascular pain and these symptoms improved after interruption of therapy . The side effects of CPZ seemed to be not more noticeable than other cephalosporins.

Res Commun Chem Pathol Pharmacol, 1980 Sep, 29(3), 445 - 58
Behavioral and electrocortical effects after intrastriatal cefazolin in rats are antagonized by drugs enhancing GABA-ergic transmission; Nistico G et al.; Cefazolin, a semisynthetic cephalosporin, reported to reproduce in several animal species an experimental model of epilepsy, was microinjected into the head of the caudate nucleus in rats . The effects on behavior, electrocortical activity and the antagonism by GABA receptor agonists and GABA-transaminase activity inhibitors were studied . Cefazolin given into the III cerbral ventricle produced an intense pattern of behavioral and locomotor stimulation culminating into several episodes of wild-running crisis, myoclonic jerks of the limbs and in some occasions generalized clonic seizures, these effects lasting over 2 h . At the same time bursts of electrocortical high-voltage spikes followed bu intermittent high-voltage single spikes were recorded . Similarly cefazolin, given into the caudate nucleus produced contralateral circling, an increase locomotor activity, myoclonic jerks of contralateral limbs, intense stereotyped behavior and occasionally generalized clonic convulsions . In addition postural changes consisting in tonic contralateral head-neck deviation were observed . This picture was accompanied by epileptic electrocortical changes, i.e . high-voltage spikes, spike-waves complexes, recruiting polyspikes . The subsequent intraventricular or intrastriatal infusion of GABA, GABOB, muscimol or of GABA-transaminase inhibitors, ethanolamine-o-sulphate and GABA-vinyl-GABA was able to antagonize clinical and electrocortical changes evoked by cefazolin . In conclusion, the present results suggest that cefazolin motor and electrocortical effects are due to an impairment of GABA-ergic transmission.

Am J Clin Pathol, 1980 Aug, 74(2), 229 - 32
Ampicillin resistance in Hemophilus parainfluenzae; Walker CN et al.; Ampicillin resistance among strains of Hemophilus is usually due to production of beta-lactamase . This paper reports the isolation of a strain of H . parainfluenzae resistant to ampicillin with no detectable beta-lactamase or amidase activity . The organism, isolated from the blood of a patient who had aortic valve endocarditis, gave a zone diameter consistent with ampicillin sensitivity when tested by disc diffusion in Mueller-Hinton agar supplemented with 1% IsoVitaleX and 1% hemoglobin . Broth dilution testing in Levinthal medium, however, revealed the following minimal inhibitory cencentrations: ampicillin, 32 micrograms/ml; penicillin, 256 micrograms/ml; methicillin, 128 micrograms/ml; carbenicillin, 128 micrograms/ml; and cephalothin and chloramphenicol, 1.0 micrograms/ml . The results of acidimetric, iodometric, and chromogenic cephalosporin methods for detection of beta-lactamase were negative . Beta-lactamase activity could not be demonstrated in cell sonicates or induced by growth of the cells in antibiotic-containing medium . In addition, no extracellular degradation of either ampicillin or penicillin could be demonstrated.

Antimicrob Agents Chemother, 1980 Jul, 18(1), 111 - 7
Regulatory properties of O-acetyl-L-serine sulfhydrylase of Cephalosporium acremonium: evidence of an isoenzyme and its importance in cephalosporin C biosynthesis; Dobeli H et al.; O-Acetyl-L-serine sulfhydrylase catalyzes the final step in the biosynthesis of cysteine from H2S and O-acetyl-L-serine in the fungus Cephalosporsium acremonium, a cephalosporin C-producing organism . We separated this enzyme from the closely related but less specific O-acetyl-L-homoserine sulfhydrylase and showed that O-acetyl-L-homoserine sulfhydrylase also catalyzes the formation of cysteine from O-acetyl-L-serine and H2S . The expression of O-acetyl-L-serine sulfhydrylase was regulated by exogenous methionine . In addition, this enzyme was inhibited by S-adenosyl-L-methionine and 5-formylpteroyl monoglutamic acid . The inhibition of both S-adenosyl-L-methionine and 5-formylpteroyl monoglutamic acid was noncompetitive . Results obtained with gel filtraton experiments in various buffer systems indicate an association-dissociation behavior of O-acetyl-L-serine sulfhydrylase.

J Pharmacobiodyn, 1980 Jul, 3(7), 364 - 6
Characterization of cephalosporin resistance in clinical isolates of Escherichia coli; Sawai T et al.; The susceptibility of 416 clinical isolates of Escherichia coli to ampicillin, cephaloridine and cefoxitin was determined, and 39 isolates were found to be resistance to 25 micrograms/ml or higher concentrations of cephaloridine . Five of the cephaloridine-resistant strains further exhibited resistance to cefoxitin which is a novel cephamycin antibiotic stable to many types of beta-lactamases . The cephaloridine-resistant strains except the strains resistant to cefoxitin produced a large amount of type I penicillinase mediated by R plasmid, while all the cefoxitin-resistant strains produced a cephalosporinase (2 strains) or both of the cephalosporinase and the type I penicillinase (3 strains) . Although the cephalosporinase failed to hydrolyze cefoxitin effectively in vitro, the close relationship between the cephalosporinase production and the cephaloridine and cefoxitin resistances in the E . coli strains was suggested . The conjugal transfer of the cefoxitin resistance to an E . coli strain was unsuccessful.

J Antibiot (Tokyo), 1980 Jul, 33(7), 783 - 6
Ro 13-9904/001, a novel potent and long-acting parenteral cephalosporin; Reiner R et al.; Ro 13-9904/001 is a novel parenteral cephalosporin antibiotic with potent in vitro activity against a wide range of beta-lactamase-producing and non-producing pathogens . In addition, Ro 13-9904/001 proved to possess a very long plasma half-life and, as a consequence, high prophylactic in vivo effectiveness.

Jpn J Antibiot, 1980 Jun, 33(6), 675 - 8
{Competitive in vitro binding of bilirubin and ceftizoxime to human serum albumin (author's transl)}; Sakamoto H et al.; The competitive effect of ceftizoxime, a new cephalosporin, on in vitro binding of bilirubin to human serum albumin was investigated and compared with that of other beta-lactam antibiotics . At the normal range of the albumin (3.48 g/dl) and bilirubin (0.936 mg/dl) concentrations in the serum of healthy infants, free bilirubin concentration was not increased by adding ceftizoxime and the other beta-lactam antibiotic concentrations tested (up to 640 micrograms/ml) . The same results were obtained even under the same condition except that the bilirubin concentration was increased to 10 mg/dl . Under the condition that the albumin concentration decreased to one fifth of the normal concentration, bilirubin was competitively displaced to some extent by adding dicloxacillin (MDIPC), cefazolin (CEZ) and cefmetazole (CMZ) but not by adding ceftizoxime at the concentration of 640 micrograms/ml.

Am J Hosp Pharm, 1980 Jun, 37(6), 858 - 9
Disulfiram-like reaction associated with a parenteral cephalosporin; Foster TS et al.; A disulfiram-like reaction attributed to cefoperazone, an investigational cephalosporin, is reported . Cefoperazone (T-1551, Pfizer Pharmaceuticals, Inc.), a semisynthetic, parenteral cephalosporin undergoing clinical trials in the United States, was administered in single 1-, 2-, and 3-g doses to 12 healthy volunteers . The drug was administered as a 5% solution by constant infusion over a five-minute period, and one week was allowed between doses . Approximately 25 hours after receiving the 3-g dose, one subject experienced facial flushing after drinking 12 fluid ounces of beer . A second ingestion of 24 ounces of beer eight hours later produced facial flushing, tachycardia, diaphoresis, and pounding headache; the symptoms lasted 1.5-2 hours . A subsequent rechallenge with beer five hours later produced an identical reaction, but the symptoms subsided rapidly . Further rechallenge 60 hours after receiving the drug produced no ill effects . No such reaction appears to have been reported previously as being associated with the administration of a cephalosporin.

Drug Intell Clin Pharm, 1980 Apr, 14(4), 272 - 7
Effectiveness of a cephalosporin education program--a pharmacy education program; Sohn CA et al.; In October, 1977, a cephalosporin drug-use review and an educational program were initiated to maximize savings in the pharmacy budget at UCSF and to revise the formulatory to include only one parenteral cephalosporin . The results of the drug-use review were presented to the Pharmacy and Therapeutics Committee where our proposal for an education campaign to encourage appropriate dosing of cefazolin was approved . An explanatory document comparing cephalosporin costs and equivalency was developed for hospital-wide distribution . Pharmacy staffs were informed of program objectives to coordinate education efforts . Physician education was undertaken via document and personal contact with pharmacy personnel . A drug-use review one month after institution of the cephalosporin education program showed marked changes in physician prescribing habits, with greater impact on services where pharmacists were members of the medical rounding team . A change to appropriate dosage prescribing of cefazolin resulted in significant cost savings to the pharmacy budget . These findings resulted in formulary revision to cefazolin as the single cephalosporin available at UCSF . Because cefazolin is available from more than one manufacturer, we were able to obtain a lower bid price the following year, thus realizing an additional cost savings.

J Pharm Pharmacol, 1980 Mar, 32(3), 182 - 7
Inhibitors of alpha-chymotrypsin derived from cephalosporins: structure-activity relationships; Hachim B et al.; Cephalothin and certain other cephalosporins are irreversible inhibitors of alpha-chymotrypsin in near neutral media . The active inhibiting species is slowly generated in small yield from cephalothin in aqueous solution . Structure-activity studies for 37 other cephalosporins and related compounds establish that inhibitors of the enzyme require in the parent cephalosporin molecule a 7-acyl substituent containing a flat area in the form of an aromatic or heterocyclic ring together with a 3-acetoxymethyl or other substituent which is labile to water . The inhibitory species is considered to be the oxazolinone derived from the corresponding cephalosporoic acid.

Biochem J, 1980 Feb 15, 186(2), 613 - 6
The conversion of cephalosporins to 7 alpha-methoxycephalosporins by cell-free extracts of Streptomyces clavuligerus; O'Sullivan J et al.; In the presence of S-adenosylmethionine, 2-oxoglutarate, Fe2+ and a reducing agent, cell-free extracts of Streptomyces clavuligerus convert cephalosporin C and O-carbamoyldeacetylcephalosporin C into 7 alpha-methoxy derivatives . No synthesis of a 7 alpha-methoxy derivative of deacetylcephalosporin C was detected in the system used, and the 7 alpha-methoxy derivative of deacetoxycephalosporin C was produced only in relatively small amounts . It appears that the 7 alpha-methoxy group is introduced after the cephalosporin ring system has been formed and that its introduction may represent the final step in a biosynthetic pathway.

Antibiotiki, 1980 Feb, 25(2), 105 - 7
{Cephalosporin C stability in aqueous solutions}; Portnoi IuA et al.; Stability of cephalosporin C in aqueous solutions at various temperatures was studied . The kinetic parameters of the inactivation process providing estimation of the inactivation rate constant of cephalosporin C at pH 0-12.5 and various temperatures were evaluated . It was found that the zinc ions had no specific effect on the inactivation rate.

Monogr Neural Sci, 1980, 5, 14 - 9
Cefazolin: a valid model of experimental epilepsy?
Nistico G, De Sarro GB, Naccari F, Musolino R, Rotiroti D, Gallitto G, Di Perri R.
In various animal species (chicks, rats and rabbits) the intravenous injection of high doses of cefazolin, a cephalosporin not hitherto reported to produce epileptic seizures, was found to produce epileptiform electrocortrical changes similar to those evoked by intravenous benzylpenicillin . Similar phenomena as those reported after systemic injection were also observed after microinjection of cefazolin into the III cerebral ventricle . In fact, both in chicks and rats cefazolin given by the latter route produced wild running crisis, myoclonic jerks of the limbs and in some instances generalized clonic convulsions . Concomitantly, bilateral electrocortical high voltage bursts of spikes were observed, followed during the intercritic period by periodic bilateral or unilateral single spikes.

Antibiotiki, 1980 Jan, 25(1), 3 - 9
{Characteristics of cephalosporin C biosynthesis on a synthetic medium}; Lur'e LM et al.; The attitude of the cephalosporin C-producing organism to various sources of carbon and nitrogen was studied . Carbohydrates such as maltose, starch and sucrose and nitrogen sources such as mineral ((NH4)2SO4 + KNO3) and organic nitrogen (asparagine) may be successfully used for the culture growth and antibiotic biosynthesis . The use of the mineral nitrogen necessitates additional regulation of pH during the cultivation process . The effect of pH on cephalosporin C biosynthesis was studied and its optimal values were found . It was shown that methyloleate played no specific role in cephalosporin C biosynthesis . It is an additional source of carbon which may be replaced by whale oil . It was demonstrated that the 1st stage of assimilation of inorganic sulfate, i.e . its reduction was blocked in C . acrimonium 218A . The study on the problem of phases in production of cephalosporin C showed that unlike the penicillin-producing organism C . acremonium had no capacity for the antibiotic biosynthesis at the early developmental stages irrespective of the cultivation conditions.

Arzneimittelforschung, 1980, 30(10), 1669 - 79
Toxicity and reproduction studies of ceftizoxime sodium; Fukuhara K et al.; Sodium (6R,7R)-7-{(Z)-2-(2-amino-4-thiazoyl)-methoxyiminoacetamido}-8-oxo-5-thia-1-azabicyclo{4,2,0} oct-2-ene-2-carboxylate (ceftizoxime sodium), a new semisynthetic cephalosporin derivative, was tested for acute toxicity in various laboratory animal species, nephrotoxicity in rabbits, subacute and chronic toxicity in rats and dogs, and effect on fertility and teratogenicity in rats and rabbits . The i.v . LD50 values of ceftizoxime sodium in mice and rats were around 6000 mg/kg, and no deaths occurred in dogs after the largest dose of 3200 mg/kg . There was no evidence of nephrotoxicity of ceftizoxime sodium in rabbits after an i.v . dose of 1000 mg/kg . Clear-cut changes in subacute and chronic toxicity studies of ceftizoxime sodium were local damage at the injection site and its secondary reactions, although reversible peripheral anemia was observed in one female dog given 1000 mg/kg i.v . In the reproduction studies, ceftizoxime sodium had no adverse effects on fertility or fetal development in rats or rabbits.

Chemotherapy, 1980, 26(4), 282 - 8
In vitro evaluation of new penicillins and cephalosporins upon P . aeruginosa and their interaction with mecillinam; Perea EJ et al.; The in vitro activity of the new semisynthetic ureidopenicillins azlocillin (AZ) and mezlocillin (MZ), and of the new cephalosporin cefsulodin (CEF) were determined against 50 carbenicillin-sensitive (CARs) and 50 carbenicillin-resistant (CARr) P . aeruginosa clinical isolates . In the CARs group the most active antibiotics are AZ and CEF with MICs between 0.5 and 8 microgram/ml . Ticarcillin (TIC) and MZ showed more activity than CAR with MICs from 2 to 32 mu/ml . In this group there is a predominance of pyocine-type groups 1 and 3 . In the CARr group, AZ is the most active antibiotic at low concentrations . At 64 microgram/ml of CEF, 72% of strains are inhibited as compared to 70% with AZ, 62% with MZ and 50% with TIC . In this group there is predominance of non-typeable strains . Interaction with mecillinam (MEC) and these antibiotics was studied on three different culture media (MH, NIH and DST) . There were few cases of synergism with MEC and TIC combinations, mostly on DST medium . No appreciable synergism was found with other combinations of antibiotics.

Med Clin (Barc), 1979 Dec 15, 73(10), 451 - 5
{Bisalbuminemia (author's transl)}; Gimenez Fernandez J et al.; A general review of bisalbuminemia is presented . Besides congenital bisalbuminemia there is an acquired form of bisalbuminemia that appears following treatment with high dosis of penicillin and cephalosporin, or in cases of acute pancreatitis after the development of a pancreatic pseudocyst . There is one type of abnormal albumin that migrates faster than normal albumin (rapid variant) and another type that is slower (slow variant) . Different subtypes of each one have been recognized . There is no immunological difference between normal albumin and the variants . From a clinical point of view, bisalbuminemia per se does not cause any observable alterations . This is an important finding, however, because of the possibility that some physiologic or pharmacologic substances may not be bound to the abnormal variants as well as to normal albumin . When bisalbuminemia appears following an episode of pancreatitis it may be indicative of a pancreatic pseudocyst.

Ann Allergy, 1979 Dec, 43(6), 337 - 40
Penicillin and cephalosporin immunogenicity in man; Delafuente JC et al.; Whether cross-allergenicity exists between the penicillin and cephalosporin antibiotics is controversial . A solid-phase radioimmunoassay was adapted to detect drug-specific IgG, IgM and IgE antibodies . Penicillin and cephalothin-specific serum immunoglobulins were determined in patients' serum before and after a therapeutic course of sodium cephalothin . Changes in IgG, IgM and IgE antipenicillin and anticephalothin antibodies, respectively, occurred and were closely correlated to one another (r = 0.80--0.99, p less than 0.0005), indicating that antibody responses to penicillin and cephalothin were linked . This in vitro assay system should prove useful for further study of clinical drug allergies.

J Pharm Sci, 1979 Nov, 68(11), 1369 - 74
Degradation kinetics of a new cephalosporin derivative in aqueous solution; Rattie ES et al.; The degradation kinetics of a new cephalosporin derivative (1) in aqueous solution were investigated at 60 degrees, mu = 0.05, at pH 2.0-10.0 . The observed degradation rates followed pseudo-first-order kinetics and were influenced significantly by H2O and OH- catalysis . No primary salt effect was observed in the acid region, but a positive salt effect was observed at pH 9.4 . A general base catalytic effect by a phosphate buffer species was observed at pH 7-8 . The pH-rate profile for I exhibited a degradation minimum at pH 6.05 . The Arrhenius activation energies determined at pH 4.0 and 9.4 were 27.2 and 24.5 kcal/mole, respectively . Excellent agreement between the theoretical pH-rate profile and the experimental data supported the hypothesized degradation process . A comparison of I and cefazolin revealed close structural and stability analogies.

Med J Aust, 1979 Oct 20, 2(8), 436 - 9
A survey of cephalosporin use . Monitoring use in a hospital setting; Arthurson SL et al.; A survey of cephalosporin use was conducted at Flinders Medical Centre, a teaching hospital incorporating most specialty services . All in-patients who were prescribed cephalosporins over a seven-week period were monitored, and an evaluation of appropriateness of use was made by means of defined criteria . The cost of usage was also determined . During the study, 55 patients were given 57 courses of cephalosporins . In 59% of courses a cephalosporin was not the drug of choice; this figure comprised 42% of 33 therapeutic and 71% of 24 prophylactic courses . In most cases, the appropriate drug would have been a penicillin, usually a penicillinase-resistant penicillin . Prophylactic courses were often longer than normal recommendations . Each course cost approximately $25, about twice that of more appropriate drugs . It is suggested that future criteria-based reviews should be conducted to identify practice deficiencies, and that guidelines for antibiotic use be created.

Am J Hosp Pharm, 1979 Oct, 36(10), 1347 - 51
Developing drug-use profiles from drug-charge records; Hlynka JN et al.; The potential for developing a drug-use profile from drug-charge records was studied at an 830-bed community hospital . Patient drug charges were reviewed retrospectively for one year (1975) to identify: (1) which key drugs accounted for a high percentage of cost and usage; (2) where key drugs were used within the hospital; (3) how they were used; and (4) who were the chief prescribers . Of the drugs used, 8% accounted for 80% of total drug product costs . Seven drug groups (10% of the total drug groups) appeared in the top 10 of both drug cost and quantity categories . Six individual drugs also appeared in the top 10 of both categories . According to cost, cephalosporin antibiotics were ranked first among drug groups but were sixth according to quantity . Analgesics-antipyretics were ranked first among drug groups by quantity and second by cost . Cephalothin was ranked first among individual drugs by cost and was not in the top 10 in quantity . Diazepam was ranked first among individual drugs by quantity and third by cost . Patients' drug-charge records can be used effectively to generate drug-use profiles for ongoing drug use review, quality assurance and cost containment programs.

Antibiotiki, 1979 Oct, 24(10), 764 - 7
{Comparative study of cephalexin and cephradine distribution in the body of rats}; Klimova VS; Distribution regularities of cephalexin and cephradine, 2 semisynthetic cephalospor in antibiotics for oral use were studied on rats . It was found that the cephalosporins had a capacity for satisfactory penetration through the histochematological barriers . The drugs were rather rapidly absorbed from the gastrointestinal tract of the rats into the blood . Their maximum blood levels were determined 1 hour after the administration . The highest cephalosporin concentrations were detected in the kidneys and liver . Still, the level of cephradine in the kidneys was lower and that in the liver was higher than the levels of cephalexin . The lowest concentrations were found in the skeletal muscles . The character of cephradine distribution in the lungs, heart and spleen differed from that of cephalexin; the maximum concentrations of cephradine in these organs were achieved 1 hour after its administration, while those of cephalexin were achieved in 30 minutes . The antibiotics were not detected in the brain tissue . No increase in the concentration gradient with time was observed.

Br J Dis Chest, 1979 Oct, 73(4), 395 - 8
Cefuroxime in severe respiratory infections: a double-blind comparison of two doses; Pines A et al.; Cefuroxime, a new cephalosporin, was given in doses of 750 mg and 1000 mg three times daily for 10 days to 99 patients in a double-blind comparison . Patients were moderately or severely ill with exacerbations of chronic bronchitis, often accompanied by pneumonia . Both doses were equally efficacious in improving the clinical state and sputum purulence and in maintaining the improvement.

Am J Obstet Gynecol, 1979 Aug 15, 134(8), 925 - 35
Perioperative cephalosporin prophylaxis in cesarean section: effect on endometritis in the high-risk patient; Kreutner AK et al.; A total of 120 patients who were to be delivered by cesarean section and who were at high risk of postoperative infection received three doses of either cefamandole, cephalothin or placebo perioperatively . Maternal serum levels for both antibiotics were in the therapeutic range . Although both drugs reduced the incidence of febrile morbidity and endometritis, only cefamandole significantly reduced the fever index . Risk factors for postoperative infections were the presence of ruptured membranes, labor, and internal fetal monitoring . Cefamandole beneficially influenced all risk factors while cephalothin was able to reduce only the risk of ruptured membranes . When a new method for obtaining endometrial tissue was utilized, 50% of cultures were negative . There was no difference in the organisms isolated from patients with and without endometritis.

Clin Chem, 1979 Aug, 25(8), 1461 - 4
An improved micromethod for theophylline determination by reversed-phase liquid chromatography; Butrimovitz GP et al.; We describe an improved micro-scale method for determining serum theophylline by reversed-phase liquid chromatography . Samples are deproteinized with two volumes of methanol containing beta-hydroxyethyltheophylline as an internal standard . The supernate is chromatographed with a methanol/sodium acetate buffer (15/85 by vol) mobile phase, and the amount of theophylline is calculated from the ratio between peak heights for theophylline and the internal standard at 273 nm . We also monitor for chemical interferences at 254 nm . We found no interferences from ampicillin, methicillin, cephalosporin, and cephalothin . None of the drugs tested or metabolites and compounds related to theophylline have been found to interfere . The method is rapid, accurate, sensitive, and specific for theophylline.

J Med Chem, 1979 Jul, 22(7), 778 - 84
Electronic structures of cephalosporins and penicillins . 9 . Departure of a leaving group in cephalosporins; Boyd DB et al.; Molecular orbital calculations by the CNDO/2 method are used to study the potential energy surface for the stretching and rupturing of the CH2-OAc bond in a model cephalosporin structure, 7-amino-3-(acetoxymethyl)-3-cephem . The bond is easier to stretch and break when a nucleophilic group is in the vicinity of or attached to the beta-lactam carbonyl carbon (C8) . The rate of acylation by a beta-lactam antibiotic at the receptor sites in bacterial cell-wall enzymes will be enhanced by a suitable leaving group at the 3' position . An orientational specificity is predicted for the direction of departure of the leaving group . Regardless of the direction the nucleophile approaches C8, the CH2-OAc bond is easiest to break when the acetate group departs from the alpha face of the molecule.

Quad Sclavo Diagn, 1979 Jun, 15 Suppl 1, 406 - 18
{Surveillance of cephalosporins therapy in therapeutic practice of 15 Italian hospitals (author's transl)}; Martini N et al.; A retrospective review and evaluation of systemic cephalosporin therapy in 15 hospitals of various italian Regions was conducted . In any hospital the Pharmacy Service has examined a random sample of medical records of hospitalized patients exposed to cephalosporin therapy over a twelve month period (January-December 1976) . In the years 1974-1976 were also examined the consumption and cost for Penicillin G, Ampicillin and Cephalosporins . A standard protocol and methodology for homogeneous collection of data was developed . On the base of collected data, the patterns of choice, the rational and irrational use, the role of cephalosporins in hospital practice are discussed.

Am Surg, 1979 Jun, 45(6), 384 - 7
Colitis and pseudomembranous colitis associated with cephazolin prophylaxis; Degan TJ et al.; Three patients suffering from colitis associated with cephalexin therapy are reported . All had undergone surgery and had previously suffered severe associated medical problems . Their presenting symptoms included profuse diarrhea, vague abdominal pain, fever and leukocytosis, but all stool cultures were negative . In one case, a pseudomembrane was present; in another only acute inflammatory changes, and in the third patient, no proctosigmoidoscopy or biopsy was done . Cephalosporin therapy was halted and bowel rest as well as intravenous hydration were instituted . All three patients survived . Inasmuch as four cases of colitis associated with cephalosporin therapy have now been treated at UCLA Hospital, the authors believe that this diagnosis should be strongly considered when patients on cephalosporin develop diarrhea.

J Pharm Sci, 1979 May, 68(5), 616 - 21
Chemical reactions in cephalosporin allergy: high-pressure liquid chromatographic analysis of cephalosporin aminolysis kinetics; Tsuji A et al.; Cephalosporin reaction with protein amino groups is fundamental to cephalosporin allergy . Cephalothin and cefazolin reaction kinetics with epsilon-aminocaproic acid, B-alanine, and glycine in aqueous solution were investigated . All reactions were conducted at 35 degrees and 0.5 ionic strength and were followed by ion-exchange high-pressure liquid chromatography . The aminolysis rate constants can be expressed as terms representing uncatlyzed or water-catalyzed amine reaction, self-assited nucleophilic reaction, and hydroxide-ion-catalayzed nucleophilic amine attack on the beta-lactam moiety . Cephalothin and cefazolin react with amines as readily as penicillin G . The UV spectra of several cephalothin-glycine reaction products were recorded, and their possible structures are discussed.

Med Klin, 1979 Apr 27, 74(17), 672 - 4
{Infection prophylaxis with cefamandole . Clinical evaluation in the open heart-surgery and the prosthetic vascular reconstruction (author's transl)}; Tschirkov A et al.; The experience with the cefamandole prophylaxis in 244 patients with open heart-surgery, and another 84 patients operated upon on prosthetic vascular reconstruction was evaluated . No case of endocarditis, sepsis or massive wound infection with infected prosthesis was found in the reviewed patients . Considering the fact that patients undergoing open heart-surgery and prosthetic vascular reconstruction are subjected to much more bacterial contamination than patients undergoing any other surgical procedure, the cephalosporin treatment (in our study cefamandole) should be considered the antibiotic of choice in preventing of infection during and after such surgical intervention.

Biochem J, 1979 Apr 1, 179(1), 47 - 52
Biosynthesis of a 7-alpha-methoxycephalosporin . Incorporation of molecular oxygen; O'Sullivan J et al.; A 7-alpha-methoxycephalosporin containing a carbamoyloxymethyl substituent at C-3 (cephamycin C) has been isolated from the extracellular fluid of an aqueous suspension of Streptomyces clavuligerus shaken in the presence of 18O2 . The cephalosporin has been converted into its N-acetyl dimethyl ester and the distribution of 18O in the latter determined by chemical-ionization mass spectrometry . The results indicate that the oxygen atom of the methoxy group, as well as that linked to the exocyclic methylene group at C-3, is derived from molecular O2.

J Chromatogr, 1979 Feb 1, 169, 343 - 50
Separation of some cephalosporin derivatives by ion-pair reversed-phase high-performance liquid chromatography; Crombez E et al.; Cephapirin, its major metabolite desacetylcephapirin, 7-aminocephalosporanic acid and some other cephalosporin derivatives are separated on a chemically bonded octadecylsilane reversed-phase column . The selectivity between cephapirin and desacetylcephapirin on the reversed-phase column is too high, resulting in a poor separation . The effect of several variations of the chromatographic conditions on the selectivity has been examined . The in situ ion-pair formation of the cephalosporins with several counter ions and the influence of the ion-pair formation on the capacity factor and on the selectivity have been investigated . Other factors, such as the temperature, combination of counter ions and nature of the organic modifier and their influence on the selectivity have also been studied.

Antibiotiki, 1979 Feb, 24(2), 109 - 14
{Comparative study of the distribution of semisynthetic cephalosporins in the body of rats}; Iakovlev VP et al.; Distribution of 6 cephalosporin antibiotics, i . e . cephaloridin, cephalotin, cephradin cephacetryl, cephazolin and cephapyrin for parenteral use was studied comparatively on rats . The studies showed that all the above cephalosporins were well absorbed into the blood after intramuscular administration . The highest serum levels were achieved with the use of cephozolin . Still, its levels in the animal organs were mainly not higher and sometimes even lower than those provided by the other antibiotics . The highest levels of cephalosporins were detected in the kidneys . Cephalotin, cephapyrin and cephacetryl differed by the character of their distribution in the rats from the other 3 antibiotics: the levels of cephalotin and cephapyrin in the heart, spleen and muscles were lower than those of the other cephalosporins; sometimes they were even not detected in these organs; cephacetryl was not found in these organs . The levels of these 3 antibiotics in the kidneys were lower than those of the other cephalosporins . Cephalotin, cephacetryl and sometimes cephapyrin were not detected in the rat liver . None of the cephalosporins was found in the brain tissue.

J Clin Microbiol, 1979 Feb, 9(2), 205 - 7
Chromogenic cephalosporin spot test to detect beta-lactamase in clinically significant bacteria; Montgomery K et al.; lactamase production . Reacteroides melaniongenicus, 14

Obstet Gynecol, 1979 Jan, 53(1), 31 - 5
Effect of single and multidose cephradine prophylaxis on infectious morbidity of vaginal hysterectomy; Mendelson J et al.; The administration of cephradine prophylactically to patients who were undergoing vaginal hysterectomies resulted in a marked and significant reduction in the incidence of postoperative infections when compared to a placebo group . Cephradine was the cephalosporin studied because of its unique pharmacodynamic properties, which result in high uterine tissue levels . The protective effect was similar whether 1 g was given preoperatively followed by 500 mg IV q . 6 hours for 4 doses, or a single dose of 2 g IV given approximately 1 hour before surgery . Uterine tissue and serum levels of antibiotic were high and correlated with the degree of protection noted.

Arzneimittelforschung, 1979, 29(10), 1544 - 6
{The influence of cephaloridine on several methods for the determination of creatinine (author's transl)}; Raasch E et al.; Cephalosporins, especially cephaloridine (Kefspor), are examined in vitro for their influence on several methods for the determination of creatinine . Two chemical methods frequently used in clinical laboratories (Jaffe test reaction) and one enzymatic creatinine analysis are used for this purpose . Depending on the quality of cephalosporin added, excessively high creatinine contents are determined with the two chemical methods, whereas there seems to be no effect on the enzymatic creatinine determination method . The significance of these findings for clinical diagnostics is discussed.

Arzneimittelforschung, 1979, 29(2a), 437 - 43
Clinical pharmacology phase I of cefazedone, a new cephalosporin, in healthy volunteers . II . Pharmacokinetics in comparison with cefazolin; Pabst J et al.; In two consecutive cross-over studies, each involving 10 healthy volunteers, the pharmacokinetics of (6R,7R)-7-(2-{3,5-dichloro-4-oxo-1(4H)-pyridyl}-acetamindo)-3-({(5-methyl-1,3,4-thiadiazol-2-yl)-thio}methyl)-8-oxo-5-thia-1-azabicyclo{4,2,0}oct-2-ene-2-carboxylic acid (cefazedone, Refosporen) in comparison with cefazolin were investigated after single i.v . and i.m . administration . The doses were: i.v . cefazedone 500 mg and 1000 mg; cefazolin 1000 mg; i.m . cefazedone 500 mg, cefazolin 500 mg . The pharmacokinetic parameters were analysed by applying an open two-compartment model . The pharmacokinetics of cefazedone are nearly identical with those of cefazolin . In particular, it must be noted that cefazedone has a relatively long serum elimination half-life (1.64 +/- 0.23 h after i.v . and 1.85 +/- 0.51 h after i.m . administration) and that cefazedone exhibits, in comparison with cefazolin, a more favourable concentration ratio of central vs . peripheral (= tissue) compartment (1:2).

Arzneimittelforschung, 1979, 29(2a), 435 - 6
Clinical pharmacology phase I of cefazedone, a new cephalosporin, in healthy volunteers . I . Tolerance in comparison with cefazolin; Ungethum W et al.; In conjunction with pharmacokinetic investigations, the tolerance of (6R,7R)-7-(2-{3,5-dichloro-4-oxo-1 (4H)-pyridyl}-acetamido)-3-({(5-methyl-1,34-thiadiazol-2-yl)-thio}methyl)-8-oxo-5-thia-1-azabicyclo{4,2,0}oct-2-ene-2-carboxylic acid (cefazedone, Refosporen), a new semisynthetic cephalosporin, was compared with that of cefazolin in two consecutive cross-over studies conducted on 10 healthy male volunteers each . The systemic tolerance of cefazedone after 1 X 500 mg and 1 X 1000 mg i.v., and 1 X 500 mg i.m . injections was very good and comparable with that of cefazolin . The same holds true for the local tolerance after i.v . administration . The local tolerance of i.m . administered cefazedone can also be classified as good when compared with that of cefazolin.

Postgrad Med J, 1979, 55 Suppl 4, 53 - 5
Cefaclor in the treatment of infections of the ears, nose, and throat; Federspil P et al.; Clinical experience and laboratory tests in 52 patients (14 to 77 years of age) who had moderate to severe ear, nose, and throat infections were evaluated in this study of cefaclor, a new cephalosporin antibiotic, The drug proved to be effective in the treatment of these infections, and the incidence of side effects was low . Patients received oral doses of 500 mg every 8 hr for three to five days after all signs of infection had disappeared . Therapeutic results were assessed as very good in 31 patients, good in 17, and unsatisfactory in one . Three were unevaluable . The rapid onset of the therapeutic effect obtained with cefaclor in these patients was particularly striking . Some side effects occurred, but they were essentially transient and minor . Cefaclor should become a major antibiotic for the treatment of infections of the ears, nose, and throat.

Can J Microbiol, 1979 Jan, 25(1), 61 - 7
Nitrogen nutrition and regulation of cephalosporin production in Streptomyces clavuligerus; Aharonowitz Y et al.; When used as sole nitrogen source, certain amino acids (e.g., proline, asparagine) supported both growth and sporulation by Streptomyces clavuligerus streaked onto solid defined medium . Ammonium supported growth but suppressed sporulation . Amino nitrogen was best for cephalosporin production in liquid defined medium, although urea was almost as useful . A comparison of amino acids showed asparagine and glutamine to be the best nitrogen sources and arginine to be almost as good . Ammonium salts supported a somewhat lower growth rate than asparagine, but antibiotic production was very poor on these inorganic nitrogen sources . Addition of ammonium to asparagine did not affect growth rate but increased mycelial mass; cephalosporin production was reduced by about 75% . Antibiotic production was more closely associated with growth in the absence of ammonium than in its presence, indicating a strong inhibitory and (or) repressive effect of NH4+ on antibiotic production . Ammonium exerted its negative effect when added at 24h or earlier, i.e . before antibiotic formation began.

Rev Infect Dis, 1979 Jan-Feb, 1(1), 99 - 105
A glimpse of the early history of the cephalosporins; Abraham EP; The cephalosporins, like the penicillins, came from research that was partly academic but that led to results which found application in medicine . A number of events followed the isolation of a Cephalosporium in Sardinia in 1945 . Research at Oxford resulted in the discovery of cephalosporin C in 1953, in the elucidation of its structure in 1959, and in the determination of many of its characteristic properties . Further work in the United States opened the way to large-scale production of a series of semisynthetic cephalosporins . A change in the attitude of the Government toward the application of academic research in the United Kingdom and the establishment of a National Research Development Corporation were responsible for certain differences between the commercial development of the cephalosporins and that of penicillin.

Postgrad Med J, 1979, 55 Suppl 4, 17 - 21
An evaluation of the toxicity of cefaclor in laboratory animals; Hanasono GK et al.; The toxicity of cefaclor, a new orally-administered cephalosporin, was evaluated in laboratory animals given single or multiple doses of the antibiotic . The acute toxicity data for cefaclor in mice, rats, dogs and monkeys were comparable to that previously reported for cephalexin . Rats were maintained on dietary mixtures of cefaclor which provided average daily doses of approximately 230 to 950 mg/kg for 28 days in subacute toxicity tests, and 160 to 675 mg/kg for 1 year in chronic toxicity tests . Treatment-related effects in the above studies were limited to soft stool excretion and caecal dilatation in the subacute test . Effects in dogs given daily oral doses of 50 to 200 mg/kg for 30 days were limited to a transient moderate fall in haemoglobin concentration in the two males at the highest dose . Soft stool excretion and occasional episodes of emesis were observed in dogs given cefaclor for 1 year at oral doses of 100 to 400 mg/kg/day . A reversible thrombocytopenia occurred in one animal at the highest dose . Analysis of various tissue fluids taken 2 hours after the last dose revealed that the concentration of cefaclor in the synovial fluid was approximatley one-half of that in serum . The results of these studies indicate that cefaclor has a low toxic potential in the species tested.

Antibiotiki, 1978 Dec, 23(12), 1108 - 12
{Phamacokinetics of methicillin, oxacillin and cephalosporin in the body of puerperae}; Kulakov VI et al.; Features of absorption, distribution and excretion of methicillin, oxacillin and cephaloridine in 58 puerpera were studied . No complications were observed in the postnatal period of the puerpera . The results of the study of the antibiotic pharmacokinetics provided elaboration of the optimal regimen for the use of methicillin, oxacillin and cephaloridine in puerpera, i . e . I g intramuscularly every 6 hours.

Am J Hosp Pharm, 1978 Dec, 35(12), 1521 - 3
Savings achieved through cephalosporin surveillance; Katz E et al.; The process by which a 427-bed, acute-care teaching hospital reduced the cost of cephalosporin therapy is described . During a nine-month surveillance period, cefazolin prescribing patterns were monitored . Of the 674 patients who received cefazolin, 640 (92%) received dosages greater than those recommended in the literature . Attempts were made to alter inappropriate prescribing through pharmacist-physician consultation and through contact with the medical service representative of the company which supplied cefazolin . Because these efforts failed, the pharmacy and therapeutics committee decided to delete cefazolin from the formulary . Cephalothin and cephapirin were found to be clinically similar; therefore, the committee recommended that the less expensive cephapirin be dispensed whenever a parenteral cephalosporin was ordered . Prior to the switch to cephapirin, cefazolin accounted for 49% of all parenteral cephalosporin use and 62% of the cephalosporin cost . Cephalothin and cefazolin were 30% and 88%, respectively, more expensive than cephapirin . In the first year after the switch, the hospital saved $33,196 (28.8% of the previous year's total expenditures for cephalosporins).

Jpn J Antibiot, 1978 Oct, 31(10), 606 - 9
{Synergistic effect of ampicillin and dicloxacillin on penicillin and cephalosporin-susceptible Escherichia coli (author's transl)}; Morohoshi T et al.; An effect of a combination of ampicillin (ABPC) and dicloxacillin (MDIPC) on penicillins and cephalosporin-susceptible E . coli was determined . Minimum inhibitory concentrations of the combined drug were as same as that of ABPC, but bacterial growth was inhibited by the combined drug stronger than ABPC, low activity of beta-lactamase was detected in sonicated E . coli 0.225 cells, and this activity was inhibited by relatively low concentration of MDIPC . We considered that a weak synergism of the combined drug might attribute to the inhibition of the beta-lactamase activity by MDIPC.

JAMA, 1978 Sep 8, 240(11), 1169 - 71
Legionnaires' disease . Clinical findings and one-year follow-up; Lattimer GL et al.; The cases of six patients with Philadelphia Legionnaires' disease were studied during the acute phase and throughout the following year . This multisystems disease process developed abruptly with symptoms of chills, fever, myalgias, and headache . The unusual clinical association of fever with relative bradycardia was noted frequently . Pneumonia developed after the first few days and rapidly progressed to life-threatening respiratory failure despite penicillin and cephalosporin therapy . Improvement occurred within 48 hours after tetracycline or chloramphenicol was administered . No permament sequelae were noted on the one-year follow-up examination, and no secondary cases of infection occurred.

Am J Hosp Pharm, 1978 Aug, 35(8), 933 - 5
Cephalosporins: use review and cost analysis; Noel MW et al.; The prescribing patterns for the cephalosporins and the cost-savings following restriction of cephalothin sodium and approval of cefazolin sodium were studied over a three-year period at a university hospital . The prescribing patterns for cefazolin relative to dose, frequency, duration of therapy and clinical indications were studied for 64 patients during a one-month period . Parenteral cephalosporin use for three years was analyzed to determine comparative use rates and costs . For the most part, cefazolin was used properly during the one-month study . The greatest misuse was as prophylactic therapy in postsurgical patients . The switch from cephalothin to cefazolin resulted in a projected annual savings of $5,500, equal to more than 10% of the hospital's expenditures for parenteral cephalosporins . The prescribed daily dose of cephalosporin dropped by one-third following the formulary change . The decision to use cefazolin as the major parenteral cephalosporin resulted in substantial cost savings.

J Antibiot (Tokyo), 1978 Aug, 31(8), 776 - 82
Alkalimetric microassay of cephalosporins; Konecny J et al.; Alkalimetric pH-stat titrations of cephalosporin C, cephacetril and their deacetyl derivatives using an acetyl esterase and beta-lactamase are described . The esterase was used to assay highly purified samples of cephalosporin C and cephacetril, and also to prepare analytically defined solutions of the deacetyl cephalosporins . Lactamase-catalyzed hydrolysis of the parent compounds was then found to generate exactly 2 equivalents of acid per mole; that of the deacetyl derivatives exactly 1 equivalent.

Schweiz Med Wochenschr, 1978 Jul 1, 108(26), 988 - 94
{Serum and joint levels of cefacetrile during its administration for septic arthritis}; Blanc CH et al.; Six patients, five of whom had normal and one impaired renal function, and all suffering from purulent arthritis caused by cephalosporin-sensitive germs, were given a seven-day course of 8 g cephacetrile daily . On the first day, 6 g were administered by continuous intravenous infusion at the rate of 500 mg/h, followed by 2 g over a further 45 min . On days 2 to 7, the patients received 2 short infusions of 4 g each at an interval of 12 h . In four patients with normal renal function, serum half-life ranged from 0.8 to 1.4 h, serum levels during continuous infusion from 19 to 31 microgram/ml, and total clearances from 265 to 434 ml/min . In one patients, these values were 1.6 h, 70 microgram/ml and 131 ml/min respectively (small volume of distribution) . The concentrations in the synovial fluid varied from 2 to 29 mcirogram/ml; they were generally lower than the serum levels, but clearly exceeded the minimum inhibitory concentrations for germs commonly present in purulent arthritis . In five patients, the synovial fluid became germ-free and the arthritis was clinically cured . In the case presenting with renal insufficiency, the serum half-life was 5.8 h . During continuous administration, a steady state was not attained; peak serum levels amo9nted to 75 microgram/ml and the total clearance to 61 ml/min . The cephacetrile concentrations in the synovial fluid were very high (26 and 67 microgram/ml) . In this case, in which the renal insufficiency associated with mycosis fungoides was present before the treatment, renal function deteriorated futher during treatment while the arthritis improved.

J Antibiot (Tokyo), 1978 Jul, 31(7), 697 - 702
In vitro activity against Escherichia coli of CGP 9000, a new oral cephalosporin; Greenwood D; The activity against Escherichia coli of a new oral cephalosporin (manufacturer's code: CGP 9000) has been evaluated in vitro . The intrinsic lytic activity of the new compound was greater than that of cephalexin, but less than that of cephalothin . As judged by regrowth studies using ampicillin resistant E . coli strains, the beta-lactamase stability of the new cephalosporin was somewhat less than that of cephalexin . When tested in an in vitro model in conditions simulating those of the treatment of bacterial cystitis, cephalosporin CGP 9000 suppressed growth of an ampicillin sensitive E . coli strain for a therapeutically acceptable period of time, but exhibited reduced activity against an ampicillin resistant E . coli strain.

Ann Dermatol Venereol, 1978 Jun-Jul, 105(6-7), 609 - 14
{Allergy to betalactamins . Diagnosis in vivo and correlations with tests in vitro (lymphocyte transformation and specific IgE) (author's transl)}; Grosshans E et al.; A comparative study of the results of skin tests and tests in vitro (lymphocyte transformation L.T . and R.A.S.T . for specific IgE) in 21 patients allergic to penicillin or penicillin-derivates revealed that tests in vivo are more sensitive and reliable than L.T . and R.A.S.T . This discordance needs future research for more valuable tests in vitro, such as specific histamine-release by leucocytes or determination of IgG4 reagins by R.A.S.T . procedure . A method of diagnosis of betalactamin hypersensitivity by skin tests, including penicilloylpolylysine, benzyl-penicillin, ampicillin and cephalosporin, is suggested; this method was experienced in 21 patients and 23 control subjects and proved to be safe and reproducible.

J Infect Dis, 1978 May, 137 Suppl, S60 - S73
The nephrotoxicity of cephalosporins: an overview; Barza M; The cephalosporin antibiotics cephaloridine and cephalothin are known to cause renal damage . Experience with newer congeners is not yet sufficient to predict their potential nephrotoxocity . The renal lesion produced by cephaloridine is primarily due to the intrinsic toxicity of this drug for the cells of the proximal renal tubule and depends upon its peculiar transport characteristics . In contrast, renal injury due to cephalothin resembles that seen with the penicillins . Thus, some instances of cephalothin nephropathy appear to be toxic in nature with a histologic picture of acute tubular necrosis, whereas others exhibit signs of hypersensitivity including rash, eosinophilia, and interstitial nephritis . Among the factors alleged to contribute to the nephrotoxicity of cephalosporins is their administration with aminoglycosides . Although the physician should be aware of the possibility of a potential adverse interaction between these groups of antibiotics, the evidence is not sufficiently conclusive to warrant avoidance of the combination when it appears to be therapeutically useful.

J Infect Dis, 1978 May, 137 Suppl, S88 - S99
Pharmacokinetics of cephalosporins in patients with normal or reduced renal function; Andriole VT; The pharmacokinetic distribution of 10 cephalosporin compounds, cephalothin, cephaloridine, cephaloglycine, cephalexin, cefazolin, cephapirin, cephradine, cephacentrile, cefoxitin, and cefamandole, in patients with various degrees of renal function was reviewed . The mean serum half-life (t1/2) of each cephalosporin compound was calculated from reported data in patients grouped according to their degree of renal function, as determined by the rate of creatinine clearance . Mean t1/2 values in patients with normal renal function were compared with t1/2 values for the same cephalosporin in patients with moderate renal failure and severe renal azotemia . The effect of hemodialysis and peritoneal dialysis on the mean serum t1/2 of each cephalosporin was also determined . The mean serum t1/2 of each cephalosporin progressively increased as the rate of creatinine clearance decreased . Hemodialysis decreases the t1/2 of cephaloridine, cephalexin, cefazolin, and cephacetrile but only minimally influences the t1/2 of cephalothin and cefamandole . Peritoneal dialysis reduces the t1/2 of cephalothin and cephaloridine but only minimally influences the t1/2 of cefazolin and cefamandole.

Transfusion, 1978 May-Jun, 18(3), 369 - 73
Hemolysis induced by cefazolin and cephalothin in a patient with penicillin sensitivity; Moake JL et al.; A patient with penicillin sensitivity, who had never received a cephalosporin antibiotic previously, developed anemia and spherocytosis following the administration of cefazolin . Hemolysis abated when the drug was discontinued on the fourth day, and recurred on day six when cephalothin therapy was begun . IgG and complement components were present on the patient's erythrocytes, and IgG antibodies in her serum reacted with normal red blood cells which had been coated with benzylpenicillin, cefazolin or cephalothin . Antibodies to cephalothin-coated red blood cells were removed partially by incubating her serum with either benzylpenicillin or cefazolin . Complement-fixing IgG antibodies which reacted with red blood cells coated by cefazolin, cephalothin, and benzylpenicillin were considered to be responsible for hemolysis during the administration of cefazolin and, subsequently, cephalothin . The patient recovered completely following discontinuation of antibiotics, transfusion of red blood cells, and treatment with glucocorticoids . It is concluded that hemolysis may occur during therapy with cefazolin, as well as cephalothin, and may develop rapidly in a patient with penicillin sensitivity.

J Infect Dis, 1978 May, 137 Suppl, S74 - S79
Immunologic cross-reactivity between penicillins and cephalosporins: a review; Petz LD; Several approaches have been undertaken in the study of possible immunologic cross-reactivity between cephalosporins and penicillins . Although the chemical structures of these compounds are similar in several respects, there are distinct differences in their degradation and transformation . Various degrees of cross-reactivity of antibodies produced in response to administration of these drugs have been demonstrated both with test systems that measure IgG and IgM antibodies and with those that measure IgE antibodies . The clinical significance of immune responses to cephalosporins is best understood in regard to immunohematologic abnormalities: positive direct antiglobulin (Coombs') tests occur in only approximately 3% of patients receiving cephalosporins; however, several cases of cephalosporin-induced immune hemolytic anemia have been reported . Clinical studies of the cephalosporins indicated that patients with a history of penicillin allergy have increased incidence of reactivity to cephalosporins, but it is impossible to determine to what extent this finding is due to immunologic cross-reactivity because penicillin-allergic patients have an increased incidence of hypersensitivity reactions to drugs immunologically unrelated to penicillins . In addition, there is evidence of specific immune response to cephalosporins that indicates independently acquired hypersensitivity rather than cross-reactivity in some patients.

Biochem J, 1978 Mar 1, 169(3), 705 - 7
The stereochemistry of beta-lactam formation in cephalosporin biosynthesis; Huddleston JA et al.; 3H and 14C from (2R,3S){U-14C,3-3H1}cysteine and (2R,3R)-{U-14C,2,3-3H2}cysteine were incorporated into cephalosporin C by Cephalosporium acremonium . Analysis of the radioactive cephalosporin C indicated that the formation of its beta-lactam ring occurs stereospecifically and with retention of configuration at C-3 of cysteine.

South Med J, 1978 Jan, 71(1), 84 - 6
Carbenicillin nephrotoxicity; Roselle GA et al.; A patient with biopsy-proven interstitial nephritis associated with nafcillin and dicloxacillin therapy developed fever, hematuria, pyuria, and renal insufficiency after the administration of carbenicilin five months later . Cephalosporin therapy was given to this patient without signs of renal toxicity . This is the first reported case of probable carbenicillin-induced interstitial nephritis and serves to emphasize the danger of giving any penicillin analogue to patients with a history of pencillin-induced interstitial nephritis.

Arzneimittelforschung, 1978, 28(6), 944 - 8
Kinetics of degradation of cefazolin and cephalexin in aqueous solution; Rattie ES et al.; The kinetics of degradation of cefazolin and cephalexin in aqueous solution were investigated at 60 degrees C and constant ionic strength over the entire pH range . The observed degradation rates were obtained by measuring the residual cephalosporin and were shown to follow pseudo-first-order-kinetics . They were influenced significantly by solvolytic and hydroxide ion catalysis . No primary salt effect was observed in the acid or basic pH region . Of the buffer systems employed in the kinetics studies only the phosphate buffer system showed a catalytic effect . The pH-rate profile for cefazolin showed a degradation minimum between pH 5.5 and 6.5 . Cephalexin did not show a pH minimum in that region . The apparent energies of activation were determined for cefazolin and cephalexin at pH 5.5 and were calculated to be 24.3 Kcal/mole and 26.2 Kcal/mole, respectively . The agreement between the calculated theoretical pH-rate profiles and the experimental points for both compounds support the hypothesis presented concerning the reactions involved in their respective degradation pathways.

J Pharm Sci, 1977 Dec, 66(12), 1767 - 9
Preparation, identification, and quantitative NMR determination of silyl derivatives of 6-aminopenicillanic acid, 7-amino-3-methyl-delta3-cephem-4-carboxylic acid, and 7-amino-3-acetoxymethyl-delta3-cephem-4-carboxylic acid; Bortesi F et al.; A rapid and accurate method for the quantitative determination of the extent and ratio of amino and carboxyl group trimethylsilylation of 6-aminopenicillanic acid, 7-amino-3-methyl-delta3-cephem-4-carboxylic acid, and 7-amino-3-acetoxymethyl-delta3-cephem-4-carboxylic acid is presented . The method utilizes NMR spectroscopy and is based on the difference in chemical shifts between N-trimethylsilyl and O-trimethylsilyl groups or, in cephalosporin derivatives, between the methyl group in the 3-position and free amino resonances . The spectra of the N,O-bis(trimethylsilyl) derivatives are discussed.

South Med J, 1977 Oct, 70 Suppl 1, 64 - 8
Pulmonary resection; Kvale PA et al.; Seventy-seven patients who had elective pulmonary resections were enrolled in a prospective double-blind study to assess the role of prophylactic antibiotics in preventing postoperative infections . Criteria for infection were strictly defined . A five-day course of a cephalosporin (2 gm/day in divided doses) was compared to an identical placebo . There were 17 infections in the 34 patients in the placebo group (50%), compared to only eight infections in the 43 patients in the antibiotic group (19%) (P = .005) . When infections unrelated to thoracotomy and minor infections were excluded, the advantage of prophylactic antibiotics proved even more evident . Fourteen thoracic infections occurred in the placebo group (41%) compared to only two thoracic infections (4.7%) in the antibiotic group (P = .0002) . No relationship of infection rate to the extent of pulmonary resection was found . A history of smoking, the presence or absence of chronic bronchitis, spirometric abnormalities, and obesity were all analyzed; none was related to the development of infection . We conclude that the routine use of perioperative antibiotics is indicated to prevent postoperative infections in pulmonary resection.

J Med Chem, 1977 Jul, 20(7), 963 - 5
Cephalosporin degradations; Dinner A; The acidic aqueous degradation of the 7alpha-aminophenylglycinamido-containing cephalosporin cephalexin (1a) has been examined . Two major degradation products have been isolated and characterized: 3-formyl-3,6-dihydro-6-phenyl-2.5(1H,4H)-pyrazinedione (5) and 3-hydroxy-4-methyl-2(5H)-thiophenone (6) . By carrying out the reaction in 18O-enriched H2O, the intramolecular nature of the cephalexin degradation has been demonstrated.

Farmaco {Sci}, 1977 Apr, 32(4), 303 - 10
Drug-protein interaction: the binding of cephalosporins to albumins; Veronese FM et al.; The binding of some cephalosporin antibiotics, namely cephalothin, cephaloridine and cephalexin, to serum albumins was quantitized using a fluorescence probe technique . The results suggest that these drugs bind to hydrophobic sites on serum albumins . The association constants of the three drugs with bovine serum albumin showed the strongest binding for cephalothin (Ka 1.2 x 10(3) M(1)) and weaker ones for cephaloridine and cephalexin (Ka 0.59 and 0.4 x 10(3) M(-1)) . Serum albumin from different species was also investigated, only minor variations in the binding properties being found.

Biochim Biophys Acta, 1977 Mar 28, 491(1), 223 - 31
Penicillin-binding proteins of Escherichia coli . Comparison of a strain carrying an R-factor and the parent strain; Ogawara H; Both from Escherichia coli K12 W3630 carrying an R-factor, R+75, and from the parent strain at least six penicillin- and cephalosporin-binding proteins were obtained as soluble forms . The molecular weights of the binding proteins of the strain carrying an R-factor were similar to those of the parent strain and not affected by the presence of an R-factor which specified the production of a beta-lactamase . Gel filtration with {14C}benzylpenicillin suggested the equimolar binding of benzylpenicillin to each binding protein . Three binding proteins of E . coli carrying R+75 and two binding proteins of the parent strain were purified by affinity chromatography followed by gel filtration . In fluorescence titration, various penicillins and cephalosporins were shown to bind to the purified binding proteins and their association constants were in the range of 0.4 to 21-10(3) M-1 . The binding proteins of both strains did not react with the antibody against the beta-lactamase specified by R+75.

J Antibiot (Tokyo), 1977 Mar, 30(3), 226 - 33
Sulfur metabolism of a mutant of Cephalosporium acremonium with enhanced potential to utilize sulfate for cephalosporin C production; Komatsu KI et al.; Characteristics of a mutant of Cephalosporium acremonium with enhanced potential to utilize sulfate for cephalosporin C production were investigated with sulfur-starved cells . DL-Norleucine showed an inhibitory effect on cephalosporin C and penicillin N production by the mutant in the presence of a sulfur source such as sulfate, sulfite, thiosulfate, and L-cystine, but it exhibited no effect when it was added after a certain period of incubation . On the contrary, antibiotic production by the parent was stimulated by norleucine regardless of the addition time . An increase in the intracellular cysteine pool was found when the cells were incubated with L-methionine or norleucine and sulfate . Enzymatic studies revealed that methionine and norleucine stimulated the cysteine desulfhydrase formation, and this effect was significant in the mutant . Finally the mutant was found to have an enhanced L-serine sulfhydrylase activity . The increase in this enzyme activity in the mutant seems responsible for the increase in the sulfate-utilizing ability and the methionine sensitivity by maintaining a high level of the cysteine pool . Accordingly, the effect of methionine and norleucine is assumed to be exerted through cysteine.

Eur J Pediatr, 1977 Jan 26, 124(2), 129 - 38
Studies on the concentrations of chloramphenicol in the serum and cerebrospinal fluid of neonates, infants, and small children . Reciprocal reactions between chloramphenicol, penicillin and phenobarbitone; Windorfer A Jr et al.; The interactions between chloramphenicol, penicillin and phenobarbitone were investigated in 383 children (premature and neonate children, infants and small children) . As expected, the chloramphenicol concentrations in the serum of the newborns was considerably higher than that of infants and small children with the same dosage of chloramphenicol . In the age group of the premature and newborn children and infants there was significantly higher total chloramphenicol concentrations with the chloramphenicol-penicillin combination than with chloramphenicol monotherapy . Addition of phenobarbitone to the combination significantly reduced the chloramphenicol concentrations in the neonates . Lowering of the serum chloramphenicol concentrations by phenobarbitone could not be statistically confirmed in the infant age group . Combinations of chloramphenicol with ampicillin, gentamycin or cephalosporin derivatives showed no influence on serum chloramphenicol concentrations . Transference of chloramphenicol from the serum to the cerebrospinal fluid was about twice as high in the acute inflammatory stage as when the meninges were no longer acutely diseased (60 and 30% respectively of the serum concentrations) . The passage of chloramphenicol to the cerebrospinal fluid showed no dependence on age.

Chemotherapy, 1977, 23(6), 416 - 23
Enterohepatic circulation of a new oral cephalosporin, FR10612, and its effect on serum and tissue levels in rats; Nishida M et al.; Serum levels of FR10612 given orally to rats persisted significantly longer than did those of cephalexin . Since the elucidation of this phenomenon observed in rats is considered to be pertinent to the understanding of the drug kinetics of FR10612 in other animals including man, the present study was undertaken . From the dose-response curve of the serum levels of FR10612 in rats, it is apparent that the maximum oral absorption is obtained in the range of 100-400 mg/kg . Even when the doses were increased from 100 to 1,000 mg/kg, the tissue levels with the exception of the kidneys, did not increase significantly . However, the persistence of the tissue levels was enhanced . The serum and tissue levels of FR10612 in rats after repeated massive dosings did not increase accumulatively . From the experimental results of FR10612 in rats with ligated bile ducts and the results obtained after intravenous injection, it seems clear that the prolonged in vivo levels of FR10612 in rats after oral dosing are closely related to its enterohepatic circulation.

Acta Med Scand, 1977, 202(6), 523 - 8
Management of septicemia and early death in acute leukemia; Lantz B et al.; Publication Types:

	Clinical Trial
	Randomized Controlled Trial

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