A Theoretical Investigation into the Pharmacodynamic Basis of Reduced Antimicrobial Efficacy in Malnutrition-Associated Immunocompromise in Northern Nigerian Populations

Malnutrition-associated immunocompromise alters the pharmacodynamic landscape for antimicrobial agents by modifying the host immune contribution to bacterial killing, yet the theoretical pharmacodynamic basis of reduced antimicrobial efficacy in malnourished northern Nigerian populations has not been formally investigated. This study conducted a theoretical and experimental investigation into the pharmacodynamic determinants of reduced antimicrobial efficacy in malnourished children and adults in Zamfara and Kebbi States, North West Nigeria. The theoretical framework development drew on the bacterial killing kinetics model integrating antibiotic pharmacodynamics with host immune function components. A prospective clinical pharmacokinetic-pharmacodynamic study enrolled 45 malnourished children with sepsis (SAM-diagnosed) and 45 adequately nourished septic controls, measuring amoxicillin-clavulanate pharmacokinetics and clinical/microbiological outcomes. An in vitro hollow fibre infection model replicating malnourished immune environment conditions (depleted immunoglobulin and complement) was established to isolate antibiotic pharmacodynamic parameters. Results demonstrated that pharmacodynamic target attainment (percentage time above MIC) was equivalent between groups, but microbiological eradication rates were significantly lower in malnourished patients (56.0 percent versus 82.2 percent; p < 0.001), implicating immune function deficits in treatment failure independent of antibiotic exposure. Hollow fibre experiments quantified the immune contribution to killing as a distinct pharmacodynamic parameter, contributing an original mechanistic understanding. The study provides an original theoretical contribution to antimicrobial pharmacodynamics in malnutrition contexts and justifies dose intensification strategies for selected antimicrobials in SAM-infected patients. Keywords: pharmacodynamics, antimicrobials, malnutrition, immunocompromise, Northern Nigeria