Africa has the highest global burden of antimicrobial-resistant infections, with 114.8 deaths per 100 000 people, with inappropriate use of antibiotics one of the key causes and the wrong drug enabling resistant bacteria to flourish and spread.
Writing in The Conversation, Fred Tenover and Nubwa Medugu say the challenge of tackling the resistance problem increases when there are gaps in three areas:
• access to effective antimicrobial agents;
• laboratory capacity to identify the source of infections; and
• funding to carry out planned solutions.
It’s essential to identify the type of infection present so that the right antimicrobial agent can be selected. Treatment guidelines stress the importance of using laboratory data to guide treatment.
Physicians need these data to choose the right antibiotic, at the right dose, for the right period – known as antimicrobial stewardship.
But in low- and middle-income countries, hospital budgets don’t include much funding for laboratories, so the data to create local treatment guidelines for doctors are scarce.
Treatment choices become “empiric” – the doctor’s best guess based on the patient’s signs and symptoms – and his or her experience. But this can lead to choosing ineffective antibiotics, which can lead to increases in resistant bacteria.
Our combined experience in understanding and addressing the spread of antimicrobial resistant organisms in African countries, and Nigeria in particular, spans 40 years. Over this time, we have noted how the lack of laboratory data hinders the effective treatment of patients with infections.
We have also observed that the cost of producing quality data is high and rising.
One way forward is to pool lab data from other hospitals in the region to guide therapeutic choices. In other words, to develop a list of what bacteria are prevalent in the region and which drugs work against them.
To accomplish this, we recently conducted a study of multidrug-resistant bacteria obtained from patients in six hospitals in northern Nigeria. Our goal was to determine which antimicrobial agents might still be effective therapies in this region.
The results indicate that the mechanisms by which bacteria have become resistant in the region are complex, but there may be ways to support antimicrobial stewardship efforts in local hospitals.
Drug-resistant bacteria in Nigeria
We chose to analyse bacteria that are resistant to more than one drug because they are the biggest challenge when treating infections. We focused primarily on bacteria from blood and urinary tract infections.
We found that about 85% of the bacteria isolated from infections were resistant to the most commonly used antibiotics. So, without lab data, the most frequent choices of antibiotics would probably be ineffective.
In addition, 65% of the bacteria analysed were resistant to the “antibiotics of last resort”.
Those are antibiotics reserved for treating the most difficult infections. This result was higher than anticipated, underscoring the need for laboratory data to indicate where antibiotic resistance was becoming a serious problem.
The good news was that two antibiotics, tigecycline and fosfomycin, remained very active even against highly resistant strains of bacteria. The bad news was that they are expensive and not readily available in many African hospitals.
Nevertheless, these data on the resistance patterns of multidrug resistant infections support the value of regional guidelines, pointing to strategies of antimicrobial stewardship that might work specifically in Nigeria.
Such strategies could include judicious use of tigecycline or fosfomycin for serious infections when guided by laboratory data.
Genetic mechanisms
Our study went beyond the use of routine testing methods and included whole genome sequencing of the resistant bacteria. This was done to understand what made these organisms so resistant to antibiotics at the molecular level.
The data revealed an astonishingly high number of genetic mechanisms making the micro-organisms resistant. This shows that the choice of agents to treat infections has not been optimal in the past.
Genes which inactivated some classes of antimicrobial agents – such as beta-lactams, aminoglycosides, tetracyclines and fluoroquinolones – were present.
In some cases, the genetic information encoding resistance was capable of being shared among other micro-organisms. This increases the potential for spread of the resistance problem.
Additionally, among the isolates studied, several belonged to newly emerging “high-risk” bacterial clones. These are bacterial species of high virulence that are easily spread among patient populations.
Hospitals need to pay closer attention to infections caused by resistant bacteria to ensure infections do not spread to other patients.
The need for antimicrobial stewardship
Some of the resistance genes were capable of moving from one micro-organism to another (mobile resistance genes). Other genes were embedded within the bacterial chromosome.
Unlike the mobile genes, which can be unstable and lost, the ones in the chromosome are often stable. This mix of mobile and embedded resistance genes suggests that resistance will not go away any time soon.
However, there is hope for decreasing the impact of resistance through effective antibiotic prescribing. Antimicrobial stewardship based on lab data is effective especially if done locally, regionally and nationally.
Antimicrobial resistance is everyone’s concern
Four points are important to note. First, similar multidrug-resistant strains of bacteria have been detected in the United States, Europe, Asia and Australia. This is a global issue.
Second, the data could have been much worse. We did identify antibiotics that are still effective even against the most resistant bacterial strains we studied.
Third, there are efforts in place in Nigeria and other African countries to limit the spread of resistant microorganisms.
Fourth, there are things that everyone can do to help bring antibiotic resistance under control.
This is a global battle that we need to win.
Fred Tenover, Distinguished Research Professor of Microbiology, University of Dayton, Ohio, USA
Nubwa Medugu, Clinical Microbiologist , Nile University of Nigeria
Study details
Phenotypic and molecular characteriwation of beta-lactam resistant Multidrug-resistant Enterobacterales isolated from patients attending six hospitals in Northern Nigeria
Nubwa Medugu, Fred Tenover, Stephen Obaro, et al.
Published in Nature on 26 June 2023
Abstract
Infections caused by multi-drug resistant Enterobacterales (MDR-E) are difficult to treat and cause significant mortality, especially in developing countries. This study characterised the phenotypic and genotypic profiles of 49 randomly selected beta-lactam resistant MDR-E previously isolated from patients being managed in hospitals in Nigeria using whole genome sequencing. The study isolates exhibited 85.5% resistance to 3rd generation cephalosporins and 65.3% resistance to carbapenems. The blaTEM-1B (29, 59.2%), blaCTX-M-15 (38, 77.6%), and blaNDM-1 (17, 51.5%) were the most common penicillinase, ESBL, and carbapenem resistant genes across isolates, respectively. Seventeen (45%) of blaCTX-M-15 was carried on the insertion sequence ISEc9 while blaNDM-1 (11, 64.7%) were associated with ISEc33. None of the 21 plasmids detected were associated with β-lactamase genes. Higher resistance rates were found in E. coli ST-88 (n = 2) and the high-risk ST-692 (n = 2). For Klebsiella species, the high-risk clones ST-476 (n = 8) and ST-147 (n = 3) predominated and had higher phenotypic resistance rates and higher number of AMR genes. The mechanisms and pattern of antibiotic resistance differ from patterns previously described with isolates harbouring a wide range of AMRGs. The detection of several chromosomally mediated carbapenemases in our study also represents a significant finding that warrants further investigation to better understand its’ implications for clinical practice and public health. The selected MDR-Es were found to be pan-susceptible to tigecycline and had very low resistance to fosfomycin, suggesting a potential for these as empiric treatments. A surveillance approach incorporating both conventional laboratory techniques and modern molecular techniques is essential for the comprehensive characterisation of the emergence and dissemination of antimicrobial resistance in Enterobacterales infections within Nigeria.
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