This case highlights the growing problem of multidrug-resistant bacterial infections in the Bahamas. Unfortunately, this case is not unique, as other authors have documented similar findings. 34 Although bacterial resistance to antibiotics has been well recognized for over a decade, the number of Bahamian patients affected is currently unknown. This article focuses exclusively on UTIs resistant to two commonly prescribed drugs. Coliform species are the most common pathogens isolated from positive urine cultures in both the outpatient and inpatient settings in the Bahamas. Historically, the overwhelming majority of presentations were uncomplicated and easily treated with oral antibiotics. However, in the primary care setting today, UTIs are becoming increasingly difficult to treat; some documented cases have even progressed to urosepsis, requiring patients to be hospitalized for intravenous management. In cases requiring hospitalization, urinary tract pathogens have been resistant to treatment with oral TMP-SMX and/or ciprofloxacin. Understanding both the mechanisms of action of the drugs and the mode by which bacteria develop resistance to them may be the best approach to mitigating this problem.

The alarming global increase in resistance to TMP-SMX 567 has serious public health implications given that TMP-SMX is the first-line treatment for uncomplicated UTIs in the Bahamas. TMP and SMX act synergistically to impede two important phases of nucleic acid and protein biosynthesis in bacteria, thus disrupting the folate synthesis pathway 8. TMP inhibits thymidine, an essential precursor for the formation of DNA, by inhibiting the enzyme dihydrofolate reductase, which is responsible for the conversion of dihydrofolate to tetrahydrofolate. SMX exerts its action by competing with para-aminobenzoic acid, thus impeding its conversion to dihydrofolic acid. Several mechanisms are responsible for the acquisition of bacterial resistance to TMP-SMX, including the development of drug-resistant genes, plasmid-coded dihydrofolate reductase, and dihydropteroate synthetase 9.

As in the above case, it has been noted that ciprofloxacin-resistant bacteria are also sometimes resistant to TMP-SMX and other antibiotic agents 10. Ciprofloxacin is a second-generation fluoroquinolone with broad-spectrum antibiotic activity. It inhibits two essential bacterial enzymes, DNA gyrase and topoisomerase IV, thereby preventing the unwinding of the DNA strand 11. Bacteria acquire resistance to fluoroquinolones via diverse and elaborate mechanisms. Correia et al. reported that the principal means involve one or a combination of target-site gene mutations that alter the drug-binding affinity of target enzymes 12. Alternative mechanisms of resistance include mutations resulting in increased efflux or decreased uptake of drugs, thereby reducing intracellular levels of fluoroquinolones and acquisition of plasmid-encoded resistance genes, leading to the formation of target protection proteins, drug-modifying enzyme, or multidrug efflux pumps.

One antibiotic that is currently being used to tackle the resistance problem in the primary care setting in the Bahamas is nitrofurantoin. Introduced in 1953, it has been proven very effective in the treatment of uncomplicated UTIs 1314. A company called Nostrum Laboratories recently acquired the rights to produce nitrofurantoin, and consequently, the drug s price has increased tremendously. Though the high cost of such an effective antibiotic may appear to be a disadvantage, one major benefit is that fewer people have access to it, thus maintaining its status as a last resort for UTI treatment. Nitrofurantoin is readily absorbed in the gut and is effective against a range of both gram-positive and gram-negative bacteria, including Enterobacteriaceae. Because of the multiplicity of its mechanisms of action, bacteria are less resistant to this drug compared with other antibiotics. Nitrofurantoin inhibits ribosomal proteins, which impedes DNA and RNA production and cell wall synthesis, causing bacterial cell death. Despite the development of resistance to other drugs, nitrofurantoin remains an effective option against UTIs in the Bahamas.