Trimethoprim-Sulfamethoxazole for Bacterial Meningitis

Abstract

Trimethoprim-sulfamethoxazole has excellent microbiologic activity against most pathogens that produce meningitis; both components of this drug have high penetration into tissues, including the cerebrospinal fluid. Clinical experience shows that trimethoprim-sulfamethoxazole may be beneficial in the treatment of gram-negative bacillary meningitis caused by organisms only moderately susceptible to third-generation cephalosporins (Enterobacter cloacae, Serratia marcescens) or resistant to these antibiotic agents (Pseudomonas cepacia, Acinetobacter). The success of trimethoprim-sulfamethoxazole in the treatment of four patients with Staphylococcus aureus and two patients with Listeria monocytogenes meningitis shows that this drug may also be useful in treating infrequent types of gram-positive meningitis.

Antimicrobial susceptibility of coagulase-negative staphylococci

“…The MICs of the combination are less than 0.1 jig/ml (20). Furthermore, the antimicrobial combination has been used with success in the therapy of such serious S. aureus infections as endocarditis and meningitis (49,54). Unfortu-nately, the emergence and dissemination of resistance to trimethoprim among CoNS preclude the use of TMP-SMX for treatment of many infections.…”

Methicillin-resistant staphylococci

“…Approximately 95% of strains are susceptible (58,140). Serious infections caused by either methicillinresistant or -susceptible staphylococci, such as cerebrospinal fluid shunt infections and meningitis, have responded to trimethoprim-sulfamethoxazole (6,102). In a randomized trial comparing trimethoprim-sulfamethoxazole and vancomycin, response rates in treatment of infections caused by methicillin-resistant strains compared with susceptible strains of S. aureus were similar (N. Markowitz, L. Saravolatz, D. Pohlod, C. Cendrowski, E. Quinn, M. Somervile, R. del Busto, J. Cardenas, and E. Fisher, Abstr.…”

Cloning and characterization of a novel, plasmid-encoded trimethoprim-resistant dihydrofolate reductase from Staphylococcus haemolyticus MUR313

“…These and other multiresistant staphylococci are a major cause of hospital-acquired infections such as bacteremias, pneumonias, and surgical wound infections (10). Although trimethoprim (Tmp) alone is not the drug of choice for the treatment of staphylococcal infections, it has been used in combination with sulfamethoxazole to successfully treat patients infected with multiresistant staphylococci (22,33). Tmp is a very selective potent inhibitor of dihydrofolate reductase (DHFR) and is active in vitro against most staphylococci, but resistance to Tmp is an ever growing problem (9).…”