Prevalence of carbapenem resistance in adult patients admitted to a private hospital in Daspoort, Tshwane
Abstract
The aim of this study was to investigate the prevalence of organisms that are resistant to the carbapenem class, in patients admitted to a private hospital. A quantitative descriptive (non-experimental) cross-sectional design was followed in order to retrospectively investigate the prevalence of resistance of hospitalised patients treated with a carbapenem between 1 January and 31 December 2014.
Mortality of patients infected with carbapenem-resistant Enterobacteriaceae (CRE) has been found to be three to six times higher compared to patients infected with carbapenem-susceptible organisms. Infections due to resistant organisms also contribute to an increased length of hospital stay and higher hospitalisation costs.
The global reported prevalence of carbapenem resistance was initially restricted to case reports and outbreaks in the intensive care unit (ICU) setting. However, a marked increase (up to 27%) has been reported in Europe and the United States (US) in recent years. Current available data in South Africa are mostly based on referred isolates of suspected carbapenemase-producing Enterobacteriaceae (CPE), which means that the prevalence of carbapenem resistance in the population at risk cannot be calculated. The World Health Organization (WHO) and the South African National Department of Health (NDoH) have identified that data regarding carbapenem resistance in Africa and specifically South Africa is incomplete and not representative of the potential burden that currently exists. The monitoring of carbapenem resistance is an important priority because this antibiotic class has been seen as the last option in the treatment for resistant gram-negative Enterobateriacae for the past two decades. Organisms that exert resistance to carbapenems are often also resistant to other antibiotics like gentamycin, the quinolone and cephalosporin classes, other ß-lactam antibiotics or ß-lactam combinations. This results in few or no treatment options for resistant organisms. Gram-negative organisms pose a specific challenge for the development of new antibiotic treatment due to its efflux-mediated resistance mechanism, which impairs the efficiency of antibiotics. This challenge is amplified by economic and regulatory constraints that have brought the development of antibiotics to a halt in recent years.
The prevalence of carbapenem resistance found in this study was 12.7% (n=9). The majority of resistance (78% of isolates) were identified through carbapenemase production based on a rectal polymerase chain reaction (PCR) swab. Two organisms, Pseudomonas putida and Enterobacter cloacae (extended spectrum ß-lactamase (ESBL) positive), expressed resistance towards a carbapenem. Pseudomonas putida exhibited resistance to imipenem, meropenem and doripenem. This specific organism has inherent resistance to ertapenem. The Enterobacter cloacae (ESBL positive) isolate was resistant towards ertapenem only. Both these organisms, initially thought to have low virulence, have emerged as difficult-to-treat infections in nosocomial infections. Literature shows that 9.6% of CRE isolates cultured in South Africa during 2014 were Enterobacter cloacae. Pseudomonas putida has to date not formally been reported as a resistant organism in South Africa.
In conclusion, the results from the current study confirm that carbapenem resistance is likely to be prevalent at all private sector hospitals in South Africa. The heterogeneity in the reported carbapenem resistance prevalence and the underrepresentation of the true burden across South Africa means that it can only be speculated on whether a prevalence of 12.7% as seen is in this study will be found in similar private hospital settings. Healthcare professionals in this hospital should use these results to improve antibiotic prescribing practices and preserve the carbapenem class as a treatment option for difficult-to-treat infections. Die doel van die studie was om die voorkoms van weerstandigheid van organismes teenoor die karbapenemklas te ondersoek in pasiënte wat in ‘n privaat hospitaal opgeneem was. ’n Kwantitatiewe beskrywende (nie-eksperimentele) deursnee-ontwerp was gevolg om die voorkoms van weerstandigheid op ’n retrospektiewe wyse te ondersoek in gehospitaliseerde pasiënte wat met ’n karbapenem behandel was tussen 1 Januarie en 31 Desember 2014.
Daar is bevind dat die mortaliteit van pasiënte wat met karbapenemweerstandige Enterobacteriaceae (CRE) geïnfekteer was, drie tot ses keer hoër was as in pasiënte wat met karbapenem-sensitiewe organismes geïnfekteer is. Infeksies wat deur weerstandige organismes veroorsaak is, dra tot ‘n verlengde hospitaliseringstydperk en hoër hospitalisasie-uitgawes by.
Die voorkoms van karbapenemweerstandigheid soos internasionaal gerapporteer, was aanvanklik beperk tot gevallestudies en uitbrake in intensiewesorgeenhede. Daar is egter ’n merkbare styging (tot 27%) in Europa en die Verenigde State in die afgelope paar jaar gedokumenteer. Huidige beskikbare data is meestal gebaseer op kwekings wat ontvang is waar karbapenemase-produserende Enterobacteriaceae (CPE) vermoed word en dit beteken dat die voorkoms van karbapenemweerstandigheid in die blootgestelde bevolking nie bereken kan word nie. Die Wêreldgesondheidsorganisasie en die Suid-Afrikaanse Nasionale Departement van Gesondheid het bevind dat data rakende karbapenemweerstandigheid in Afrika, maar meer spesifiek in Suid-Afrika onvolledig is en nie die omvang van die potensiële probleem wat tans bestaan voldoende weerspieël nie. Die monitering van karbapenemweerstandigheid is ’n belangrike prioriteit aangesien hierdie antibiotikumklas tydens die afgelope twee dekades beskou is as die laaste keuse in die behandeling van weerstandige gram-negatiewe Enterobacteriae. Organismes wat weerstandig is teenoor karbapenems, is ook dikwels weerstandig teenoor ander antibiotika soos gentamisien, die kinoloon- en kefalosporien-klasse, ander betalaktaamantibiotika of betalaktaamkombinasies. Die gevolg is dat daar min of geen behandelingskeuses vir weerstandige organismes bestaan nie. Gram-negatiewe organismes bied ’n spesifieke uitdaging vir die ontwikkeling van ’n nuwe antibiotiese behandeling weens die uitvloeibemiddelde weerstandbiedende meganisme wat die doeltreffendheid van antibiotika verswak. Daarmee saam het die ontwikkeling van antibiotika gedurende die afgelope paar jaar tot stilstand gekom weens ekonomiese en regulatoriese beperkings. Die voorkoms van karbapenemweerstandigheid wat in hierdie studie gevind is, was 12.7% (n=9). Weerstandigheid (78% van die gevalle) is meestal geïdentifiseer deur karbapenemaseproduksie in ’n anale depper (PCR-swab). Twee organismes Pseudomonas putida en Enterobacter cloacae (ESBL-positief) het weerstandigheid teenoor ’n karbapenem antibiotikum getoon. Pseudomonas putida het weerstandigheid teenoor imipenem, meropenem en doripenem getoon. Hierdie spesifieke organisme toon ’n inherente weerstandigheid teenoor ertapenem. Enterobacter cloacae (ESBL-positief) was slegs weerstandig teenoor ertapenem. Beide hierdie organismes is aanvanklik gesien as minder virulent, maar het egter ontwikkel tot infeksies wat veral in nosokomiale omstandighede moeilik is om te behandel. Literatuur het aangetoon dat Enterobacter cloacae geïdentifiseer is in 9.6% van CRE in Suid-Afrika gedurende 2014. Pseudomonas putida is tot op hede nog nie formeel as ’n weerstandige organisme in Suid-Afrika aangemeld nie. Die voorkoms van karbapenemweerstandigheid wat in hierdie studie gevind is, was 12.7% (n=9). Weerstandigheid (78% van die gevalle) is meestal geïdentifiseer deur ‘n polimerase-kettingreaksie anale depper (PCR-swab). Twee organismes, Pseudomonas putida en Enterobacter cloacae (uitgebreide spektrum ß-lactamase (ESBL) positief), het weerstandigheid teenoor ’n karbapenem antibiotikum getoon. Pseudomonas putida het weerstandigheid teenoor imipenem, meropenem en doripenem getoon. Hierdie spesifieke organisme toon ’n inherente weerstandigheid teenoor ertapenem. Enterobacter cloacae (ESBL-positief) was slegs weerstandig teenoor ertapenem. Beide hierdie organismes is aanvanklik gesien as minder virulent, maar het egter ontwikkel tot infeksies wat veral in nosokomiale omstandighede moeilik is om te behandel. Literatuur het aangetoon dat Enterobacter cloacae geïdentifiseer is in 9.6% van CRE in Suid-Afrika gedurende 2014. Pseudomonas putida is tot op hede nog nie formeel as ’n weerstandige organisme in Suid-Afrika aangemeld nie.
Die resultate van hierdie studie bevestig dat karbapenemweerstandigheid heel moontlik voorkom in alle privaatsektor hospitale in Suid-Afrika. Die heterogenetiese verskille in die voorkoms van die aangemelde karbapenemweerstandigheid en die ondervermelding van die ware toedrag van sake in Suid-Afrika, beteken dat die voorkoms van 12.7% gevind in hierdie studie nie noodwendig in soortgelyke privaathospitaal omgewings gevind sal word nie. Professionele verskaffers van gesondheidsorg in hierdie hospitaal behoort hierdie resultate te gebruik vir die verbetering van antibiotikum voorskryfpraktyke en die bewaring van die karbapenemklas as behandelingsopsie vir infeksies wat andersins moeilik behandelbaar is.
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