trimethoprim--sulfamethoxazole-drug-combination and trimethoprim-sulfamethizole

Antimicrobial resistance is a major and emerging threat worldwide. New antimicrobials have been unable to meet the resistance challenge, and treatment options are limited for a growing number of resistant pathogens. More and more clinicians are relying on older antimicrobials for the treatment of multidrug-resistant (MDR) bacteria. Some older antimicrobials have maintained excellent in vitro activity against highly resistant pathogens. In some instances, use of older agents is limited by unfavourable pharmacokinetic/pharmacodynamic characteristics and/or toxicities. In general, clinical data pertaining to the use of older agents for the treatment of MDR pathogens are scarce. Research efforts should be focused on the evaluation of older agents for the treatment of MDR pathogens as well as evaluating how these agents perform in complex patient populations with various and multiple co-morbid conditions.

Topics: Aminoglycosides; Anti-Bacterial Agents; Drug Combinations; Drug Resistance, Multiple, Bacterial; Fosfomycin; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Polymyxins; Sulfamethizole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

The gap between the emergence of antibiotic resistance and new antibiotic development has drawn attention to old antibiotics whose spectrum of coverage frequently comprises highly resistant bacteria. However, these antibiotics have frequently not undergone the structured process of antibiotic development of modern antibiotics, from pharmacokinetic/pharmacodynamic (PK/PD) studies establishing safe and effective dosing, establishment of susceptibility breakpoints, to clinical trials establishing clinical safety and effectiveness. In this review, we highlight the gaps for which we need old antibiotics in community- and hospital-acquired infections. Reviewing recently published and ongoing randomised controlled trials (RCTs) shows advances in our understanding of the efficacy and effectiveness of oral fosfomycin, mecillinam and nitrofurantoin for cystitis, and of trimethoprim/sulfamethoxazole for complicated skin infections caused by methicillin-resistant Staphylococcus aureus (MRSA) in the community. Summarising older evidence shows the inferiority of chloramphenicol versus modern antibiotics for severe infections. We lack studies on severe infections caused by carbapenem-resistant Gram-negative bacteria and other multidrug-resistant (MDR) bacteria in hospitalised and critically ill patients; ongoing studies assessing colistin and intravenous fosfomycin might fill in some gaps. In the re-development process of old antibiotics, we mandate modern PK/PD studies comprising special populations as well as RCTs addressing the target population of patients in need of these antibiotics powered to examine patient-relevant outcomes. Structured antibiotic re-development from the laboratory to evidence-based treatment recommendations requires public funding, multidisciplinary collaboration, international co-ordination, and methods to streamline the recruitment of critically ill patients infected by MDR bacteria.

Topics: Amdinocillin; Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Cross Infection; Drug Combinations; Drug Resistance, Multiple, Bacterial; Evidence-Based Medicine; Fosfomycin; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Nitrofurantoin; Staphylococcal Skin Infections; Sulfamethizole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Bacteria; Bacterial Infections; Cambodia; Child; Colony Count, Microbial; Drug Combinations; Drug Resistance, Bacterial; Drug Resistance, Fungal; Drug Therapy, Combination; HIV Infections; Humans; Kenya; Sulfamethizole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination