In vitro activity and beta-lactamase stability of cefodizime, an aminothiazolyl iminomethoxy cephalosporin

Abstract

Cefodizime, an iminomethoxy aminothiazolyl cephalosporin similar to moxalactam and ceftazidime, was less active (minimal inhibitory concentration, 1.6 to 12 p.g) than cefazolin or cefotaxime against Staphylococcus aureus and Staphylococcus epidermidis. It inhibited Haemophilus and Neisseria spp. at <0.5 ,ug/ml. It did not inhibit methicillin-resistant staphylococci, enterococci, or Listeria spp. and was 8-to 32-fold less active than cefotaxime, moxalactam, or ceftazidime against Escherichia coli, Citrobacter spp., Klebsiella pneumoniae, Providencia spp., and Serratia spp. Cefotaxime-resistant Enterobacter cloacae, Citrobacter freundii, and Proteus vulgaris were resistant to cefodizime. Cefodizime was less active than cefoxitin or moxalactam against Bacteroides fragilis. Cefodizime was not hydrolyzed by common plasmid or chromosomal ,-lactamases, and it inhibited type I ,-lactamases.The introduction of the iminomethoxy group on the acyl side chain of the dihydrothiazime ring of the cephalosporine nucleus and the presence of the aminothiazolyl group have provided increased activity against Enterobacteriaceae while retaining much of the gram-positive activity of the earlier cephalosporins (3). Cefodizime is structurally similar to cefotaxime but has a 1-mercapto-1,3-thiazole chain substituted for the acetoxy group at position 3 of the dihydrothiazine ring (J. Bacterial isolates were obtained from patients recently hospitalized at the Columbia-Presbyterian Medical Center, New York, N.Y. In addition, organisms which were known to be multiply resistant to antibiotics and to contain previously characterized ,B-lactamases were used in some experiments. These isolates had been stored frozen for a number of years.Antimicrobial activity was measured by an agar dilution method with Mueller-Hinton agar unless specified otherwise. Fresh dilutions of the compounds were prepared daily in sterile medium or distilled water. A final inoculum of 105 CFU prepared by dilution of a fresh overnight broth culture was applied as a spot to the agar with a replicating device. Broth dilutions were performed in 1-mi (volume) tubes with a final inoculum of 105 CFU. Plates or tubes were incubated at 350C for 18 h. The minimal inhibitory concentration (MIC) was defined as the lowest concentration of antibiotic that inhibited visible growth on agar or in broth. The minimal bactericidal concentration (MBC) was determined by plating 0.1-ml amounts from clear 1-mi broth tubes onto blood agar plates. The MBC was defined as the concentration at which there was no growth after 24 h of incubation at 35C. The susceptibility of streptococci was determined by using Muelier-Hinton agar supplemented with 5% sheep blood. The susceptibility of Neisseria and Haemophilus spp. was determined on chocolate MuellerHinton agar incubated in the presence of 5% CO2.

Randomized comparative study of 0.5 and 1 g of cefodizime (HR 221) versus 1 g of cefotaxime for acute uncomplicated urogenital gonorrhea

“…The MICs of cefodizime against penicillinase-producing and non-penicillinase-producing N. gonorrhoeae ranged from c0.004 to 0.06 ,ug/ml and corresponded with the values found in previous in vitro studies (4,8).…”

“…The use of ,-lactamase-stable chemotherapeutics may aid in the reduction of treatment failures. Cefodizime is a new ,-lactamase-stable chemotherapeutic (8) for parenteral use. It has the same structure as cefotaxime, with a 1-mercapto-1.3-thiazole chain on the third position of the dihydrothiazine ring.…”

Antibiotics and Energy Delivery to the Phagocytosis-Associated Respiratory Burst in Chronic Hemodialysis Patients: A Comparison of Cefodizime and Cotrimoxazole

“…The positive influence of cefodizime on a number of variables of the immune system was first assumed from preclinical investigations, where greater efficacy than ex pected from in vitro findings [26][27][28][29] was observed in infec tion models [30], even considering its favorable kinetic profile. This was also true for pathogens against which • cefodizime was less active in vitro than comparative drugs.…”

In vitro and in vivo Enhancement of Bactericidal Activity of Phagocytes against <i>Klebsiella pneumoniae </i>treated with Subminimal Inhibitory Concentrations of Cefodizime

“…The ma jority of Klebsiella isolates possess a well-de fined capsule which plays an important role in conferring resistance to host defence mecha nisms such as phagocytes in the absence of specific anticapsular antibodies [2], Cefodizime is a cephalosporin that is stable against various (1-lactamases and has an exten sive antibacterial spectrum against gram-posi tive and gram-negative bacteria [3]. Cefodi zime has been reported to be more potent in vivo than in vitro [4,5], to be maintained in the blood and tissue at higher concentrations and for longer periods than other (1-lactam anti biotics [8], to directly enhance phagocytic function [7,8] and to affect the immune sys tem [9,10], At a subminimal inhibitory concentration (sub-MIC), antibiotics cannot kill bacteria, but they have been shown in vitro to affect bacteria in various ways, i.e., suppression of bacterial growth [11], induction of morpholog ical changes in the bacteria [12], alteration of the cell surface structure [13][14][15], suppression of enzyme and toxin production [16] and sup pression of bacterial adhesion to host cells [17].…”