A Comparative Evaluation of Moxalactam: Antimicrobial Activity, Pharmacokinetics, Adverse Reactions, and Clinical Efficacy

Abstract

Although moxalactam is not, technically speaking, a cephalosporin it is chemically and microbiologically so closely related to those compounds that it can be viewed as a member of the cephalosporin family. Moxalactam has a spectrum of activity that includes both gram positive and gram negative bacteria. Its gram positive activity is less than earlier cephalosporins, but its activity against the Enterobacteriaceae is similar to that of the aminoglycoside family of antibiotics in most comparative studies. Although moxalactam is considerably less active against gram positive bacteria than cefotaxime, another third generation cephalosporin, its higher and more prolonged serum levels probably offset this disadvantage. Compared to cefoperazone, the stability of moxalactam to many types of beta lactamases produced by gram negative bacteria may be advantageous in the therapy of infections caused by hospital-acquired pathogens. Clinical studies suggest that moxalactam can be used for empiric therapy of suspected gram negative infections when Pseudomonas and other non-fermentative bacteria, such as Acinetobacter, are not suspected. Impressive improvements in the survival of patients with gram negative enteric bacillary meningitis have been reported. Although moxalactam, cefotaxime, and cefoperazone have activity against Pseudomonas aeruginosa, none of these antibiotics should be used alone as therapy for suspected or proven severe systemic infections caused by this pathogen. Cost is a major problem with all of the new cephalosporin-like antibiotics. While this high cost may be partially balanced by the use of a single agent compared to an antibiotic combination for therapy in some situations, these antibiotics are not cost effective for prophylactic use. Superinfection with fungi, such as Candida, and Streptococcus faecalis have occurred, and toxicities, such as bleeding due to vitamin K deficiency and disulfuram-like reactions, have also been reported. Reports of resistance to moxalactam and the other third generation cephalosporins are of major concern and indicate the need to closely monitor antibiotic susceptibility patterns of hospital acquired organisms if these antibiotics are to be used for empiric therapy of suspected gram negative non-pseudomonas sepsis.

Imipenem coadministered with cilastatin compared with moxalactam: integration of serum pharmacokinetics and microbiologic activity following single-dose administration to normal volunteers

“…However, clinical studies have identified problems when patients with some Pseudomonas aeruginosa infections are treated with moxalactam. In addition, the activity of moxalactam against many gram-positive bacteria, including penicillinase-producing Staphylococcus aureus strains, is less than the activity of the first-generation cephalosporins (6). Imipenem, a new beta-lactam antibiotic, has the broad spectrum required to treat sepsis that is presumed * Corresponding author.…”

Optimizing Therapeutic Drug Monitoring in Pregnant Women: A Critical Literature Review

“…Azlocillin, cefazolin, imipenem, moxalactam, phenoxymethylpenicillin/penicillin V, and piperacillin are mostly eliminated by glomerular filtration, with some of them also eliminated by active secretion dependent on organic anion transporter (OAT) 1 and 3 or the multidrug resistance protein 4 (MPR4). 68,81,89,114,116–118…”

“…Azlocillin, cefazolin, imipenem, moxalactam, phenoxymethylpenicillin/penicillin V, and piperacillin are mostly eliminated by glomerular filtration, with some of them also eliminated by active secretion dependent on organic anion transporter (OAT) 1 and 3 or the multidrug resistance protein 4 (MPR4). 68,81,89,114,[116][117][118] Other antibacterial drugs also undergo biliary elimination without the renal route, such as ceftriaxone [renal OAT 1/ 3 and hepatic organic-anion-transporting polypeptides (OATP) 1B3] and cefotaxime (renal OAT 3 and MRP4 and hepatic OATP1B3) or just biliary elimination such as cefoperazone (OATP1B3). 68,114,119 Therefore, this review highlights the importance of quantifying the effect of pregnancy on the activity of drug transporters because glomerular filtration alterations are already well known.…”

Latamoxef dosing regimen adjustments and pharmaceutical care in pediatrics

“…The MIC 90 of Staphylococcus aureus ( S. aureus ) strains ranged from 4 to 16 µg/ml. Latamoxef has similar activity against penicillin-resistant and -sensitive strains of S. aureus , but methicillin-resistant S. aureus is resistant to latamoxef (MIC 90 > 64 µg/ml) ( 15 – 18 ). The MIC 90 of latamoxef for Streptococcus pneumoniae ( S. pneumoniae ) and Streptococcus pyogenes ( S. pyogenes ) varies from 1 to 3 μg/ml ( 18 ).…”

“…Hypersensitivity may occur in approximately 2%–3% of patients treated with latamoxef and consist of symptoms including rashes, occasional fever, and eosinophilia ( 1 , 18 , 47 ). This was the most common reason for stopping treatment ( 1 ).…”