Cephapirin

A specific, stability-indicating, high-performance liquid chromatographic assay was developed for the determination of cephapirin, desacetyl cephapirin and cephapirin lactone in sodium cephapirin (cefadyl) bulk and injectables. The procedure uses a muBondapak C18 column and a mobile phase of dimethylformamide-acetic acid-potassium hydroxide in water. UV detection at 254 nm is used for quantitation with acetanilide used as the internal standard. The assay is precise, accurate and linear over the range of 100-300 micrograms/ml for cephapirin and over the range of 2-6 micrograms/ml for desacetyl cephapirin and cephapirin lactone. The assay is also stability-indicating for the described thermal, acid, base, aqueous and accelerated light degradations.

Cephapirin, a new semisynthetic cephalosporin derivative, was found to have an antibacterial spectrum similar to that of cephalothin. Staphylococcus aureus was inhibited by cephapirin concentrations of 0.09 to 12.5 mug/ml. S. epidermidis, S. viridans, S. pyogenes, and Diplococcus pneumonia isolates were inhibited by less than 1 mug/ml. The Enterococcus required a concentration of 25 mug of antibiotic per ml for inhibition. Approximately 65% of Escherichia coli, and all Klebsiella, indole-negative Proteus, and Salmonella strains tested were inhibited by the drug. Serratia, Pseudomonas, indole-positive Proteus, and Erwinia strains were highly resistant. Inoculum size was not an important factor in determining the level of sensitivity of S. aureus to cephapirin. The antibiotic does not appear to be significantly bound to serum protein. In vitro development of resistance to the drug was demonstrated with two isolates of S. aureus.

Five cases (3.5%) of reversible cephapirin-induced neutropenia were observed in 132 patients receiving this antibiotic. The disorder was severe (agranulocytosis) in 3 cases. Simultaneous maculopapular rash was observed in all of them and in 4 cases fever occurred. All the cases observed were female (p not significant). Neutropenia developed only after administration of high doses of the antibiotic for a prolonged period of time. In contrast to another 127 patients treated with cephapirin who did not develop neutropenia, neutropenic patients had received a mean daily dose, total dose, mean daily dose per kilogram and total dose per kilogram of body weight significantly larger (p = 0.05, 0.02, 0.001 and 0.001, respectively). The duration of therapy was significantly longer in the neutropenic group (p = 0.001). Neutropenia did not occur below 90 g of total dose, but when this amount was exceeded, the incidence of the disorder reached 26.3% (p less than 0.001). We conclude that when this drug must be used either for long periods of time or at high doses, a hematologic vigilance is recommendable.

Cows in estrus but with signs of clinical endometritis (CE) are often not inseminated or undergo an intrauterine treatment after artificial insemination (AI). Decades ago, the so-called Aström method was described as intrauterine infusion of iodine-potassium solution 2-4 days after AI. Nowadays, it is common to use antibiotics instead of iodine solution and the treatment is performed only a few hours after AI. Although widespread in practice, there is only little information about the efficacy of this treatment. Thus, this study evaluated the effect of a post-breeding intrauterine treatment with cephapirin on insemination success in cows with signs of mild CE. In total, 281 cows subjected to an Ovsynch program with fixed-time AI and examined for vaginal discharge straight after AI by use of the Metricheck device were included. Cows with cloudy discharge or flecks of pus in the mucus were assigned to a treatment or a control group. The treatment group (MET; n = 87) received 6 ± 1 h after AI an intrauterine treatment with 500 mg of cephapirin (Metricure, Intervet Deutschland GmbH). Control cows (CON; n = 91) remained untreated. Animals with clear discharge were assigned to a healthy comparison group (HE; n = 103). Pregnancy diagnosis was performed 39 days after AI. The proportion of pregnant cows after the AI directly preceding the enrollment did not differ significantly (P > 0.05) between HE (35.0%), CON (27.5%) and MET (32.2%). Cephapirin treatment had also no positive effect on other reproductive performance measures, i.e, the percentage of pregnant cows 200 days after enrollment (HE: 64.1%, CON: 73.6%, and MET: 73.6%) or the mean interval from enrollment to conception (HE: 25.4 days, CON: 30.0 days, and MET: 29.7 days). The binary logistic regression showed that the only risk factors with a detrimental effect on fertility were a history of CE 28-34 days postpartum and season. Although cows in MET and HE were 1.74 and 1.37 times more likely to conceive after AI than CON, this effect was not significant. Uterine sampling of a subset of cows with CE (n = 50) revealed 127 bacterial isolates. The most frequently found genera were Staphylococcus (19.7%), Bacillus (12.6%), Streptococcus (10.2%), Corynebacterium (8.7%), and Lysinibacillus (7.9%). The finding that common uterine pathogenic bacteria were rarely detected additionally questions an intrauterine antibiotic treatment of cows with mild CE at AI.