Double beta-lactam therapy may not sound appealing, but it might be more widely applicable than you think
A 🧵
1. Enterococcus faecalis endocarditis
•Ampicillin + ceftriaxone has comparable efficacy but less toxicity versus ampicillin + aminoglycoside
•Works by complementary PBP binding of the 2 agents
•May not be applicable to Enterococcus faecium
•For those with risk factor for Listeria (e.g. age >50, alcoholic, immunocompromised), ampicillin should be added to empirical 3rd generation cephalosporin
•If somehow meropenem is used, additional ampicillin is not necessary
1.General
•1st generation parenteral cephalosporin
•Active against MSSA, Streptococci (A,B,C,G,viridans) and aerobic GNB (E.coli, Klebsiella, Proteus)
•2 most common indications: MSSA BSI, pre-op prophylaxis
2.MSSA BSI
•Both cefazolin and anti-staphylococcal penicillins (ASP) are recommended treatment options for MSSA BSI
•Synergism when combined with ertapenem (complementary PBP binding, action on biofilm, ?effect on immune response) pubmed.ncbi.nlm.nih.gov/31773134/
3.MSSA BSI (cont')
•Compared with ASP: similar efficacy in general, fewer side effects (e.g. nephrotoxicity, phlebitis), more convenient dosing esp in renal impairment
•2 most common concerns for cefazolin: inoculum effect, CNS penetration
1. Spectrum
•Broad (Yes it is) aerobic and anaerobic coverage (MSSA, Enterococcus, Bacteroides, common Gram -ve e.g. E.coli, even ESBL if for UTI)
•Also potentially useful for melioidosis, capnocytophaga, certain nocardia, etc
2. WHO Group D3 anti-TB
•Regarded as possessing anti-TB activity, either by itself or in combination with meropenem/imipenem (mainly for the clavulanate component)
•Should only be considered in MDR setting when there are no better alternatives
3.Oral formulations
•Different ratio of amoxicillin:clavulanate available (2:1, 4:1, 7:1. 16:1)
•Dose of clavulanate limited to 125mg max to reduce toxicity
•Narrower ratio with more frequent dosing (e.g. 500/125 tds vs 875/125 bd) may be more efficacious esp for Gram -ve
• Covers Gram +ve incl MSSA, Gram -ve incl Pseudomonas, and anaerobes incl Bacteroides
• Good for empiric treatment of neutropenic fever, intra-abdominal infection, nosocomial sepsis
2. Important caveats
• Does not cover MRSA
• Not recommended for CNS infection, due to poor BBB penetration esp for tazobactam
• ESBL/AmpC producers ➡️ meropenem is preferred (MERINO and MERINO-2)
3. Important caveats (cont)
• Enterococcus ➡️ usually active against Amp-S E.faecalis, but penicillin susceptibility is more predictive of its activity
• i.e. Amp-S Pen-R E.faecalis may not be susceptible to Pip-tazo