In this study, we describe findings of antibiotic resistance pattern and trends in comparison with PPS findings of frequency of antibiotics use. One of the significant findings from PPS was that all antibiotics in the wards were prescribed empirically (100%) without a microbiological indication. Both the PPS and the patients’ antibiotic history records in the lab indicate frequent use of certain antibiotics classes including cephalosporins, tetracyclines and penicillins. The resistant pattern of such antibiotics has shown to be considerably higher based on trends seen over the past four years. Shortage of appropriate antibiotics as well as unrevised guidelines are partly contributing to misuse as well as over use of certain antibiotics.
The consistently decline in sensitivity of the most locally used antibiotics including Ciprofloxacin, Ceftriaxone, Gentamycin, Tetracycline, Doxycycline, Amoxicillin/clavulinic acid, and Ampicillin signifies the growing resistances of common bacterial isolates due to overuse of antibiotics [14]. According to the findings of the PPS, Ceftriaxone and Metronidazole were the leading antibiotics prescribed in the wards. As observed in the antibiotic history of STI return clients, metronidazole, gentamycin and doxycycline were as well leading prescribed antibiotics as they form the main treatment package in the syndromic management approach [15, 16]. Overall, Ceftriaxone and Metronidazole were the most frequent prescribed antibiotics at the facility. The findings are in agreement with other studies conducted in sub-Saharan African region that found penicillins, ceftriaxone and metronidazole to be the most prescribed antibiotics with extended prescribing of up to 6 days or more post-operatively to prevent surgical site infections [17].
High use of ceftriaxone, metronidazole and other beta-lactam antibiotics in the wards is a cause for worry. The implications are quite grave. The emergent of highly resistant burgs will likely to lender our last line treatments ineffective. Therefore, there is great need to tackle inappropriate antibiotic use from all fronts. Evidence from PPS locally and in African region have also revealed poor compliance to available national treatment guidelines [13]. The consequent of such indiscriminate use of broad spectrum antibiotics are very costly. Hospital stewardship programmes should aim at safeguarding those antibiotics by establishing measurable antimicrobial use targets, such as reducing the use of broad-spectrum antibiotics, complying with treatment guidelines and revamping microbiology labs to increase the uptake of antimicrobial susceptibility testing to guide prescriptions [13].
In this study, it was also observed that less commonly used chloramphenicol antibiotic maintained its effectiveness against some resistant strains of bacteria. This is an agreement with other studies that found chloramphenicol maintaining its efficacy against eye infections compared to tetracyclines and floroquinolones [18]. Much as there is a growing concern of toxicity associated with chloramphenicol, randomized controlled trials (RCTs) have demonstrated that Chloramphenicol is as safe as treatment alternative for short antibiotic courses [19]. Others infrequently used antibiotics which exhibited effectiveness against certain resistant strains of gram positive cocci bacteria included Vancomycin, Fusidic acid and clindamycin. Rotation of antibiotics could be one of the many ways to adopt if we are to maintain sensitivity profile of certain antibiotics [20]. More RCT studies are required on old and less frequent used antibiotics to ascertain the effectiveness against MDR isolates.
The growing cases of recurrent infections in the STI department due to emerging gentamycin resistances have been reported in Malawi and abroad [10, 21]. STI suspected resistances are perpetuated by the syndromic management approach which rarely makes use of laboratory investigations to guide treatment based on the specific etiological agents. This study established several cases of gentamycin resistant Neisseria gonorrhoeae as well as co-infections among STI patients which could be one of the reasons for return visits after initial treatment. Return clients also presented with candida albicans with either staphylococcus sp or gentamycin resistant N. gonorrhoeae.
It is important to note that frequent antibiotics prescribed to patients with suspected STI predispose them to more other vaginal pathogens due to an imbalance vaginal flora. Studies have established an association between certain antibiotics such as tetracyclines, ciprofloxacin, ofloxacin, norfloxacin, cefixime, azithromycin and fosfomycin with subsequent occurrence of the Vulvovaginal candidiasis (VVC) [22, 23, 24]. This support the growing need to intensify the use of evidence-based treatment for STI patients, particularly those returning after the initial first line treatment. Laboratory investigations of STI cases are therefore crucial in directing clinicians and other prescribers on the right treatment in the face of multidrug resistances and co-infections.
Data for this study provides alternative therapeutic options for making clinical decisions when faced with MDR suspected cases. For instance, Methicillin resistant staphylococcus aureus (MRSA) detected by a 30 µg cefoxitin disk antibiotic expressed resistance towards cephalosporins, floroquinolones, penicillins and macrolides but were usually susceptible to Vancomycin, Chloramphenicol, Tobramycin, Amikacin, Nitrofurantoin, and Tetracycline. The findings are supported by other previous studies which also found MRSA expressing 100% resistance to penicillins such as ampicillin and 100% sensitivity to Vancomycin [12]. MRSA as well as the intrinsically resistant Pseudomonas aeruginosa are the common cause of hospital acquired infections that make a successful empirical therapy much more difficult to achieve [25].
Another interesting finding in this study is that all the cases of the intrinsically resistant pseudomonas aeruginosa (PA) were from hospitalized patients with exposed wounds that never responded to first line treatment. AST results indicate that PA was highly resistant to major antibiotics classes including cephalosporins, penicillins, Carbapenens, Macrolides, Floroquinolones and Tetracyclines. However, most patients with P. aeruginosa responded to an extended dose of gentamycin (IV) even though in vitro AST indicated partial sensitivity. With the remarkable capacity of P. aeruginosa to confer resistance via multiple intrinsic mechanisms, most antibiotics are rendered ineffective, hence a second antimicrobial agent from a different antibiotic class is often administered concomitantly with a traditional antipseudomonal β-lactam modified with inhibitors such as pipellacilin-tazobactam [26].
Most of the antibiotics found to have good sensitivity such as Tigecycline and Ertapenem are not included in the Malawi essential medicines list which is a set back on the prescribing of such drugs are they are most likely not be available in our facilities. PPS identified gaps including poor compliance to national standard treatment guidelines and stockouts of antibiotics which to some extent lead to wrong prescriptions. Pathogens exposed to sub-optimal antibiotic concentrations create selective pressure, an important precondition for the increase in multi-resistant strains [28]. Antimicrobial stewardship (AMS) committees need to intensify sensitization campaigns among healthcare workers on the importance of complying with the available national treatment guidelines as well as use of lab based evidence in making empirical prescriptions. Hospital management team as well as drug and therapeutic committees (DTC) has role to play in ensuring that necessary antibiotics are available to avoid unnecessary alternative treatments which may predispose patients to future MDR infections.
STUDY LIMITATION
At the time point prevalence was conducted, some antibiotics were out of stocks. This might have affected the outcome of PPS interms of the prevalence of antibiotics use. It was also difficult to determine whether all antibiotics tested over the past four years maintained their effectiveness or not as they were suggested to varying storage conditions. The sample size for antibiotics resistant pattern data reviewed was comparatively small to other referred studies done in hospital settings. This is because we only targeted suspected MDR cases on return patients or those with prolonged hospital stay. However, the combination of hospital ward findings from PPS and laboratory AMR data improved the validity as well as reliability of the study findings.