Monobactams and Other β-Lactams

Other β-lactam antibiotics

• Newer classes of β-lactam antibiotics include monobactams, carbapenems, and carbacephems
• These agents have a β-lactam structure but are neither penicillins nor cephalosporins

Monobactams

• Aztreonam is a monobactam isolated from chromobacterium violaceum
• Only monobactam in clinical use
• Features a β-lactam ring but lacks a thiazolidine ring
• Antimicrobial activity differs from other β-lactam antibiotics, resembles that of an aminoglycoside
• Primarily affects aerobic gram-negative microorganisms
• Gram-positive bacteria and anaerobic organisms are resistant
• Stable to most β-lactamases elaborated by gram-negative bacteria
• Administered via i.m. or i.v.
• Achieves therapeutic concentrations in CSF in the presence of inflamed meninges
• Preferred for gram-negative infections in patients with renal impairment where aminoglycosides should be avoided
• An alternative to cephalosporins for therapy of meningitis caused by gram-negative bacilli
• May be safe for patients with allergies to other beta-lactams, except those with a specific allergy to ceftazidime
• Shows cross-sensitivity with ceftazidime
• Effective against Pseudomonas and most GNRs
• Moderately effective against Acinetobacter
• Poor activity against Gram-positive organisms and anaerobes

Carbapenems

• Carbapenems include Imipenem, meropenem, and ertapenem
• All Carbapenems are β-lactam antibiotics
• Administered parenterally only
• Distributed very well throughout the body
• Can penetrate the blood-brain barrier (BBB)
• Carbapenems have a very broad spectrum of activity
• Stable against cleavage from many beta lactamases and ESBL bacteria
• Effective against Gram-negative aerobes like Enterobacteriaceae, Klebsiella, Pseudomonas, and Neisseria
• Effective against Gram-positive cocci like Strep. Pneumoniae
• Effective against Anaerobes
• Not effective against Enterococcus faecium, Burkholderia cepacia, and MRSA
• Used for severe and serious infections caused by resistant organisms, multiple organisms, febrile neutropenia, and hospital-acquired pneumonia
• Ertapenem has a narrower spectrum of activity
• Less active against Pseudomonas, Acinetobacter, and Gram-positive Enterococci and S. Pneumoniae

Carbapenemase

• Focus on understanding ESBL: definition, diagnosis, classification, and treatment

Imipenem

• Derived from a compound produced by Streptomyces cattleya
• Features a mechansim of action is the same as penicillins
• Bactericidal
• Resistant to hydrolysis by β-lactamase
• Marketed in combination with cilastatin
• Cilastatin inhibits degradation by renal dipeptidase
• Without cilastatin, renal dehydropeptidases inactivate the drug, resulting in low urinary tract concentrations and nephrotoxicity
• Adverse effects include nausea, vomiting, and seizures
• Patients allergic to other β-lactam antibiotics may have hypersensitivity reactions

Meropenem

• Comparable therapeutic effectiveness to imipenem
• Cilastin coadministration is not required
• Less likely to cause seizures compared to imipenem

Ertapenem

• Differs from imipenem and meropenem; has a longer serum half-life
• Cilastin co-administration is not required
• Less seizure-producing compared to imipenem
• Ertapenem is a poor choice for many nosocomial infections
• Particularly not effective for nosocomial pneumonia involving Pseudomonas and Acinetobacter
• Administered only once a day, is more convenient than other carbapenems
• Chosen for home-infusion therapy for susceptible infections

General Carbapenem Info

• All carbapenems are administered parenterally (i.v. or i.m., the latter may be painful)
• Imipenem is administered every 6 hours
• Meropenem is administered every 8 hours
• All are resistant to β-lactamases
• All are bactericidal
• They all share the same mechanism of action
• Patients allergic to other β-lactam antibiotics may have hypersensitivity reactions to carbapenems

Therapeutic Uses

• Used to treat urinary tract infections
• Used to treat lower respiratory tract infections
• Used to treat Intra-abdominal & gynaecological infections
• Used to treat skin, bone, joint, & soft tissue infections
• Used for Especially cephalosporin/ penicillin resistant nosocomial bacteria.

Difference Between Carbapenems

• Imipenem/cilastatin poses the highest risk potential for seizures
• Meropenem has the same spectrum of activity as imipenem but with fewer seizures
• Doripenem has a lower rate of resistance emergence in P. aeruginosa and the least risk of seizures
• Ertapenem is less active against aerobic gram-positive bacteria, P. aeruginosa, and Acinetobacter spp
• Ertapenem only requires once-per-day dosing

Carbacephems

• Loracarbef is a synthetic β-lactam antibiotic
• Similar to cefaclor
• Antibacterial activity resembles second-generation cephalosporins