Reduced intracellular drug accumulation augments fluoroquinolone and -lactam drugs resistance in clinical Gram negative bacteria from Nigeria

In Nigeria, quinolones and β-lactam antibiotics are widely used as broad-spectrum antibiotics to treat infections caused by various Gram-negative pathogens. The outer membrane is the major permeability barrier limiting target access to quinolones and other drugs in Gram-negative bacteria. This study aimed to identify the role of outer membrane porins (OMPs) and uptake in fluoroquinolone (FQ) and β-lactam drugs accumulation. In total, 134 non-duplicate, Gram-negative bacilli isolates of 13 species from different hospitals were investigated for susceptibility to a panel of antibiotics, including loss of outer membrane porins and measuring active efflux. The minimum inhibitory concentrations (MIC) results showed level of resistance to many antibiotics was extremely high having MIC90 value of 256 µg/ml or higher for all drugs, most importantly fluorquinolones, ciprofloxacin; sparfloxacin or third generation cephalosporin, ceftazidime; ceftriaxone. SDS-PAGE revealed different outer membrane porin (OMP) profiles on the basis of relative mobility among the strains. The majority of the isolates lack OMPs. The steady-state concentration of drug taken up by the isolates was measured; most of the strains accumulate less bis-benzimidine than the control strain, Salmonella enterica L354. The isolates from University College Hospital, Ibadan accumulate fewer drugs and they are more resistant with high minimum inhibitory concentrations when compared with the rests of the hospitals. Active efflux either singly or in tandem with OMPs alterations could be responsible for the low accumulation of fluoroquinolone and β-lactam antibiotics seen in this study and their increased resistance to both important classes of antibiotics.