This study describes the resistance profile of clindamycin (lincosamide), cefepime (fourth generation cephalosporin) and meropenem (carbapenem). In 2017 these antibiotics were reserved for use at tertiary hospitals following the WHO recommendation as a key focus to antibiotic stewardship (12,19). The study found the overall resistance to clindamycin, cefipime and meropenem to be 70.1%, 72.4% and 8.5% respectively, which was higher than previous studies conducted in Tanzania (14,15,20).
The study also found resistant pathogenic bacteria in the collected samples as previously reported by Nyambura et al, who did the study at BMC (20). Sadly, most of the blood samples collected in this study had resistant S. aureus which was suggestive of bloodstream infection as evidenced by more than 18% of patients who had fever. It has been documented that, S.aureus was the leading cause of blood stream infection acquired in hospital settings (21–23). S.aureus get access to blood through intravascular devices such as central venous catheters, peripheral intravenous catheters, arterial catheters and urinary catheter (21,22). Thus presence of such microorganisms that are introduced through invasive procedures such as incision, intubation, puncture, and drug injections could greatly contribute to long hospital stays as results of bacteremia(21). Bloodstream infection have been reported to be more common among children similar to our study (22,23).
Bloodstream infection is associated with high mortality rate, morbidity and prolonged hospital stay making the treatment more complicated in face of increased resistant S. aureus (21,24). Our study found 68.4% of tested S.aureus were resistant similar to Mshana et al, study in 2009 that found 61% of MRSA were resistant to clindamycin (14). Clindamycin is one of the potential alternative in high prevalent MRSA infections (25). The observed increased proportion of resistance could suggest extensive use of the antibiotic that leads to increase in resistance with time (26). In this study, Enterococcus spp isolates were found in urine and blood samples thus posing risk for development of urinary tract and bloodstream infections respectively similar to what has been reported previously(20). Most (88.9%) of the Enterococcus spp were resistant to clindamycin similar to the study by Azin et al who found the 96% resistance to clindamycin in Iran (27). It has been documented that the Enteroccoci are intrinsically resistant to clindamycin, which could explain the observed resistant pattern (8,28). Being normal flora of the gastrointestinal tract with frequent contact to antibiotics which are, in high rate misused, could increase the proportion of resistant Enterococci(9,29,30). Also, the previous use of clindamycin as additive drug to quinine for treatment of uncomplicated malaria in pregnant could have accelerated the resistance of this antibiotic (31).
Most of the Gram negative pathogens in this study were resistant to cefipime which is the fourth cephalosporin generation antibiotic for instance, 75.6% Klebsiella Spp, 93.8% P. aeruginosa, 75.0% A.baumannii, and 56.3% E.coli were resistant. This pattern of resistance is comparable to the previous study that was conducted at BMC, the proportion of resistant Gram negative bacteria was 80.6%, 87.5% and 63.2% in the order of Klebsiella spp, P.aeruginosa, 56.3% E.coli (20). The slight observed difference in proportion could be attributed to the difference in generations of cephalosporin used. Their study assessed the susceptibility of Gram negative bacteria using third generation cephalosporin (ceftriaxone/cefotaxime)(20), contrary to our study in which we used fourth generation cephalosporin (cefepime). Indeed, the observed high proportion of resistant bacteria was almost similar to the overall proportion of resistant Gram negative bacteria to third generation cephalosporin in Africa (3). These bacteria are among the most mutating bacteria with high risk to human health (1,32). The high proportion of resistant Gram negative bacteria to fourth generation cephalosporin (cefepime) could be suggestive of bacteria adaptive mechanisms by cross-resistance between generations of the same antibiotic class (32). The overuse and irrational use of antibiotics especially third generation cephalosporin (ceftriaxone) could contribute to failure of subsequent cephalosporin generations (29,30,33).
Pseudomonas aeruginosa and Klebsiella spp were isolated in all samples, this could have contributed to bloodstream infection, wound infection, urinary tract and respiratory tract infections as previously described. About 31.2% of the tested P. aeruginosa isolates were meropenem resistant contrary to the study by Sabrina et al who reported 8.9% of resistant Pseudomonas aeruginosa. Their study was conducted between 2010–2011, more than eight years ago. The trend of increasing resistant P.aeruginosa was noted in a study that evaluated clinical isolated at BMC from 2007 to 2012 that found the prevalence of resistant P.aeruginosa to be 19.5% (15). A systematic review on antibiotic resistance in Africa found P.aeruginosa to be one of the bacteria resistant to carbapenem (34). The trend of increasing bacteria strains resistant to meropenem is threatening since this drug serve as the last weapon for most of Gram negative bacteria resistant to the commonly used antibiotics.
Furthermore, we found meropenem resistant Klebsiella spp to be 8.5% which was higher than the previous study by Martha et al (1.5%) who conducted the study at BMC (15). The increase in proportion of resistant P. aeruginosa and Klebsiella Spp could indicate heightening of antibiotic resistance with time necessitating questioning the effectiveness of the control measures in place. High susceptibility observed to some of pathogenic bacteria such as A.baumannii and Proteus spp could indicate good performance in some bacteria though the increasing resistance to some highly mutating bacteria is warranting strict control measures. Carbapenems are considered the treatment of choice and last option for the common nosocomial infection caused by P. aeruginosa resistant to other β-lactam antibiotics (35). Inappropriate use of antibiotics such as carbapenems especially in private health facilities could increase the prevalence of resistant bacteria to carbapenems; pressure from pharmaceutical companies and intending to make profit could be contributing factors (36–38) .
Limitations
This study is one of few studies conducted in East Africa that assessed the resistance pattern of clindamycin, cefepime and meropenem, however, most of the previous studies did not include cefepime which is the fourth generation cephalosporin and clindamycin(34,35), hence the current susceptibility pattern of these antibiotics has limited index comparator. Our study aimed at evaluating the current status of antibiotic resistance burden in our settings after the implementation of WHO stewardship program of reserving some antibiotics to be used as last resort when multidrug resistant infection is encountered. Therefore, we focused only to survey the resistant pattern of clindamycin, cefepime and meropenem. Being a cross-sectional design, the clinical outcomes of patients from which the resistant bacteria were isolated were not documented, therefore these findings should be interpreted with cautions because they don’t equate to clinical outcomes. Furthermore, whether the infection was community or hospital acquired was not evaluated. The mechanisms of resistance and the molecular markers were not the scope of this study. In addition, this study was conducted at two tertiary teaching hospitals excluding other tertiary hospitals in the country hence should be generalized with high precaution.