Emergence of invasive Carbapenem Resistant Enterobacteriaceae CRE infection at RCWMCH Ombeva Oliver Malande, Annerie du Plessis, Colleen Bamford, Brian Eley Presenter: Ombeva Malande Red Cross Children's Hospital Paed ID /University of Cape Town Friday 6 November 2015: Session:- Paediatric ID Update
Emergence in SA of CRE with NDM-1 gene, KPCs, is worrying. MDR Gram-negs/CRE is a home-grown problem, generated and perpetuated by doctors, nurses and allied healthcare workers in South Africa. Increasing reliance on nephrotoxic colistin producing colistinresistant Pseudomonas, Klebs, & Acinetobacter No new antibiotics against Gram-negs in the antibiotic pipeline for the next 10-20 years. We must return to rational antibiotic prescribing through strong antibiotic stewardship, with equal emphasis on IPC to prevent spread of already resistant bacteria between patients.
In Africa, NDM - in SA, Kenya, Egypt, Morocco; while OXA 48 - Egypt, Senegal, Tunisia, Algeria, Morocco, SA KPC - SA and Tunisia. First SA case of NDM-1 gene in a patient from Gauteng in August 2011 Recent case in KZN in Nov 2012 that described a possible similarity between this NDM case with those seen in India. Brink AJ, Coetzee J, Clay C, et al. South Africa. J Clin Microbiol 2012; 50:525-527. Brink AJ, Coetzee J, Clay C, et al. S Afr Med J 2012;102;599-601.
CRE infection cases at Red Cross Hospital 7 cases since Nov 2012 June 2015 6 female, 15months median age (IQR 4-60) All were HCAI, with median length from hospitalization to CRE of 21 days (15-27) Median stay post CRE infection was 21days (IQR 15-27); and median duration of admission of 37 days (23-63 range) All the 7 were HIV negative, all Klebsiella pneumoniae, sensitive to amikacin and colistin Only 2/7 had a positive Hodge test, one had New Delhi Metallo-beta-lactamase (NDM) gene, one Guiana Extended-Spectrum (GES) gene, and the remaining 5 tested negative for carbapenemases.
CRE infection cases at Red Cross Hospital 4/7 BSI; 2/7 intra-abdominal sepsis, 1/7 pneumonia 4/7 developed CRE while in PICU 4/7 2 prior courses of carbapenems, 2/7 I prior course. (3 mero, 2 erta, 1 both) 4 underlying chronic infection, (3- chronic liver disease, 1 DCMO + carditis in CCF) Outcome 4 were discharged, 2 died with 16 days of CRE, 1 died after 30 days. All who died got colistin monotherapy All who were treated successfully got combination of colistin and imipenem
CRE Colonized cases at Red Cross Hospital May-June 2013-88 children screened, 7 found to be colonized with CRE on rectal swabs, Up to March 2015, another 5 sporadic cases of CRE colonisation (1/5 in Nov 2013, one February 2014, and 3 in May 2014. Thus total of 12 CRE colonized cases (9/12 female, 1/12 infant and 4/12 >5years old. All 12 cases - HIV negative, 1 exposed, but PCR Neg. All the 12 - prior exposure to a carbapenem, most to Meropenem. A few had both meropenem and ertapenem or meropenem and imipenem. All the 12 isolates were sensitive to colistin; 8 to tigecycline, 6 to amikacin, 5 to ciprofloxacin and 4 to cotrimoxazole.
CRE Colonized cases at Red Cross Hospital All 12 cases showed resistance to ampicillin, amoxicillin, co-amoxiclav, cefuroxime, cefotaxime, cefotriaxone, genta, pip-tazobactum, imipenem, meropenem and Ertapenem. 3/12 - died during that admission, one was transferred out, 8/12 treated fully. 10/12 - Klebsiella pneumoniae, 1/12 - Klebsiella oxytoca, the other grew Klebsiella Escherichia coli. 6/12 - NDM gene, with 2/12 GES gene, one had both GES and NDM while the rest tested negative. 8/12 - a positive Modified Hodge test result.
Trends in Carbapenem consumption at RCWMCH for 2005-2014 Meropenem - most consumed Imipenem - least consumed From 2005-2014, there was a steep (1,887%) increase in use of erta, 13.9% mero, 566.7% imi and 24% for colistin. After 2010, there has been a relative decrease in meropenem consumption that coincided with rise in ertapenem consumption
Discussion Points The lack of reports on CRE in children in African medical setting could be masking an underlying emergence of CRE in these settings A high index of suspicion is needed In the laboratory - to detect these genotypes, as phenotypic expression may vary. For clinicians look out for kids with risk factors The rapid detection of CRE (KPC, NDM-1, OXA-48), is essential in order to institute appropriate antibiotic treatment, as well as implement timely infection control measures, to prevent their transmission. Horizontal transfer of these genes to different plasmids can occur - playing a major role in its widespread dissemination. Need for novel IPC measures within institutions
Discussion Points Combination therapy with two active drugs Colistin + a carbapenem of favourable MIC. Tigecycline, and intravenous fosfomycin are other options. All CRE isolates were sensitive to both amikacin and colistin. Can this be a reliable combination therapy option for CRE infections? Continued surveillance and regular publication of antimicrobial resistance patterns Further molecular study of carbapenem resistance mechanisms - improve understanding of the underlying risk factors for acquisition, how to better position antibiotic stewardship in IPCs.