#Linezolid #resistance in patients with drug-resistant #TB and treatment failure in South Africa (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Linezolid resistance in patients with drug-resistant TB and treatment failure in South Africa

Sean Wasserman, Gail Louw, Limpho Ramangoaela, Garrick Barber, Cindy Hayes, Shaheed Vally Omar, Gary Maartens, Clifton Barry, III, Taeksun Song, Graeme Meintjes

Journal of Antimicrobial Chemotherapy, dkz206, https://doi.org/10.1093/jac/dkz206

Published: 12 May 2019




Limited data exist on clinical associations and genotypic correlates of linezolid resistance in Mycobacterium tuberculosis. We aimed to describe mutations and clinical factors associated with phenotypic linezolid resistance from patients with drug-resistant TB at two public sector facilities in South Africa.


Adults and adolescents with treatment failure (culture positivity ≥4 months) on a linezolid-containing regimen were retrospectively identified. Phenotypic resistance, as defined by a linezolid MIC >1 mg/L, was assessed for retrieved isolates using broth microdilution. Targeted sequencing of rrl and rplC was performed, irrespective of growth on subculture.


Thirty-nine patients with linezolid-based treatment failure were identified, 13 (33%) of whom had phenotypic or genotypic linezolid resistance after a median duration of 22 months (range = 7–32) of linezolid therapy. Paired MIC testing and genotyping was performed on 55 unique isolates. All isolates with phenotypic resistance (n = 16) were associated with known resistance mutations, most frequently due to the T460C substitution in rplC (n = 10); rrlmutations included G2814T, G2270C/T and A2810C. No mutations were detected in isolates with MICs at or below the critical concentration.


Linezolid resistance occurred in a third of patients with drug-resistant TB and treatment failure. Resistance occurred late and was predicted by a limited number of mutations in rrl and rplC. Screening for genotypic resistance should be considered for patients with a positive culture after 4 months of linezolid therapy in order to optimize treatment and avoid the toxicity of ineffective linezolid therapy.

Topic: phenotype – mutation – south africa – treatment failure – linezolid
– drug-resistant tuberculosis


Keywords: Antibiotics; Drugs Resistance; Linezolid; Tuberculosis; S. Africa.



#Klebsiella pneumoniae ST307 with #blaOXA-181, #SouthAfrica, 2014–2016 (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 25, Number 4—April 2019 / Research

Klebsiella pneumoniae ST307 with blaOXA-181, South Africa, 2014–2016

Michelle Lowe1, Marleen M. Kock, Jennifer Coetzee, Ebrahim Hoosien, Gisele Peirano, Kathy-Ann Strydom, Marthie M. Ehlers, Nontombi M. Mbelle, Elena Shashkina, David B. Haslam, Puneet Dhawan, Robert J. Donnelly, Liang Chen1, Barry N. Kreiswirth, and Johann D.D. Pitout

Author affiliations: University of Pretoria, Pretoria, South Africa (M. Lowe, M.M. Kock, K.-A. Strydom, M.M. Ehlers, N.M. Mbelle, J.D.D. Pitout); National Health Laboratory Service, Pretoria (M. Lowe, M.M. Kock, K.-A. Strydom, M.M. Ehlers, N.M. Mbelle); Ampath Laboratories, Pretoria (J. Coetzee, E. Hoosien); Calgary Laboratory Services, Calgary, Alberta, Canada (G. Peirano, J.D.D. Pitout); University of Calgary, Calgary (G. Peirano, J.D.D. Pitout); Rutgers University, Newark, New Jersey, USA (E. Shashkina, L. Chen, B.N. Kreiswirth); Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA (D.B. Haslam); New Jersey Medical School, Newark (P. Dhawan, R.J. Donnelly)



Klebsiella pneumoniae sequence type (ST) 307 is an emerging global antimicrobial drug–resistant clone. We used whole-genome sequencing and PCR to characterize K. pneumoniae ST307 with oxacillinase (OXA) 181 carbapenemase across several private hospitals in South Africa during 2014–16. The South Africa ST307 belonged to a different clade (clade VI) with unique genomic characteristics when compared with global ST307 (clades I–V). Bayesian evolution analysis showed that clade VI emerged around March 2013 in Gauteng Province, South Africa, and then evolved during 2014 into 2 distinct lineages. K. pneumoniae ST307 clade VI with OXA-181 disseminated over a 15-month period within 42 hospitals in 23 cities across 6 northeastern provinces, affecting 350 patients. The rapid expansion of ST307 was most likely due to intrahospital, interhospital, intercity, and interprovince movements of patients. This study highlights the importance of molecular surveillance for tracking emerging antimicrobial clones.

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Oxacillin; Klebsiella pneumoniae; South Africa.


Experimental #infection of racing #pigeons (Columba livia domestica) with highly pathogenic Clade sub-group B #H5N8 #avian #influenza virus (Vet Microbiol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Vet Microbiol. 2018 Dec;227:127-132. doi: 10.1016/j.vetmic.2018.10.028. Epub 2018 Nov 2.

Experimental infection of racing pigeons (Columba livia domestica) with highly pathogenic Clade sub-group B H5N8 avian influenza virus.

Abolnik C1, Stutchbury S2, Hartman MJ3.

Author information: 1 Department of Production Animal Studies, Faculty of Veterinary Science, University of Pretoria, Private Bag X04, 0110, South Africa. Electronic address: celia.abolnik@up.ac.za. 2 Department of Production Animal Studies, Faculty of Veterinary Science, University of Pretoria, Private Bag X04, 0110, South Africa. 3 Department of Companion Animal Clinical Studies, Faculty of Veterinary Science, University of Pretoria, Private Bag X04, Onderstepoort, 0110, South Africa.



Reported mass mortalities in wild pigeons and doves during the 2017/2018 Clade HPAI H5N8 outbreaks in South Africa necessitated an investigation of healthy racing pigeons for their susceptibility and ability to transmit a Clade sub-group B virus of South African origin. Pigeons challenged with medium (104.5 EID50) and high doses (106 EID50) but not a low dose (103 EID50) of virus, shed virus in low levels of <103 EID50/ml from the oropharynx and cloaca for up to eight days, with peak shedding around 4 days post challenge. Challenged pigeons were able to transmit the virus to contact pigeons, but not contact chickens. Neither pigeons nor chickens presented clinical disease, and only two pigeons in the group that received the high challenge dose developed influenza A-virus specific antibodies. The levels of virus shed by the racing pigeons were well below the published bird infectious dose 50 values for most poultry, especially chickens, therefore the risk that racing pigeons could act as propagators and disseminators through excretion of Clade HPAI H5N8 strains remains negligible.

Copyright © 2018 Elsevier B.V. All rights reserved.

KEYWORDS: Chickens; Clade; Highly pathogenic avian influenza; Pigeons

PMID: 30473343 DOI: 10.1016/j.vetmic.2018.10.028 [Indexed for MEDLINE]

Keywords: Avian Influenza; H5N8; Poultry; South Africa.


Analysis of a subacute sclerosing #panencephalitis (SSPE) Genotype B3 virus from the 2009/10 South African #measles #epidemic shows hyperfusogenic F proteins contribute to measles virus infection in the #brain (J Virol., abstract)

[Source: Journal of Virology, full page: (LINK). Abstract, edited.]

Analysis of a subacute sclerosing panencephalitis (SSPE) Genotype B3 virus from the 2009/10 South African measles epidemic shows hyperfusogenic F proteins contribute to measles virus infection in the brain.

Fabrizio Angius, Heidi Smuts, Ksenia Rybkina, Debora Stelitano, Brian Eley, Jo Wilmshurst, Marion Ferren, Alexandre Lalande, Cyrille Mathieu, Anne Moscona, Branka Horvat,Takao Hashiguchi, Matteo Porotto, Diana Hardie

DOI: 10.1128/JVI.01700-18



During a measles virus (MeV) epidemic in 2009 in South Africa, measles inclusion body encephalitis (MIBE) was identified in several HIV-infected patients. Years later, children are presenting with subacute sclerosing panencephalitis (SSPE). To investigate the features of established MeV neuronal infections, viral sequences were analysed from brain tissue samples of a single SSPE case and compared with MIBE sequences previously obtained from patients infected during the same epidemic. Both the SSPE and the MIBE viruses had amino acid substitutions in the ectodomain of the F protein that confer enhanced fusion properties. Functional analysis of the fusion complexes confirmed that both MIBE and SSPE F protein mutations promoted fusion with less dependence on interaction by the viral receptor-binding protein with known MeV receptors. While the SSPE F required the presence of a homotypic attachment protein MeV H in order to fuse, the MIBE F did not. Both F proteins had decreased thermal stability compared to the corresponding wild-type F protein. Finally, recombinant viruses expressing MIBE or SSPE fusion complexes spread in the absence of known MeV receptors, with MIBE F-bearing viruses causing large syncytia in these cells. Our results suggest that alterations to the MeV fusion complex that promote fusion and cell-to-cell spread in the absence of known MeV receptors is a key property for infection of the brain.



Measles virus can invade the central nervous system (CNS) and cause severe neurological complications such as MIBE and SSPE. However, mechanisms by which MeV enters the CNS and triggers the disease remain unclear. We analysed viruses from brain tissue of individuals with MIBE or SSPE, infected during the same epidemic, after the onset of neurological disease. Our findings indicate that the emergence of hyper-fusogenic MeV F proteins may be associated with infection of the brain. We also demonstrate that hyper-fusogenic F proteins permit MeV to enter cells and spread without the need to engage nectin-4 or CD150, known receptors for MeV that are not present on neural cells.

Copyright © 2018 American Society for Microbiology. All Rights Reserved.

Keywords: Measles; Subacute Sclerosing Panencephalitis; Measles Inclusion Body Encephalitis; Viral pathogenesis.


#Outbreak of #MDR #TB in [#ZA] South Africa undetected by #WHO-endorsed commercial #tests: an observational study (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Outbreak of multidrug-resistant tuberculosis in South Africa undetected by WHO-endorsed commercial tests: an observational study

Ndivhuho A Makhado, MSc, Edith Matabane, MSc, Mauro Faccin, PhD, Claire Pinçon, PhD, Agathe Jouet, PhD, Fairouz Boutachkourt, BSc, Léonie Goeminne, BSc, Cyril Gaudin, PhD, Gugu Maphalala, MSc, Patrick Beckert, PhD, Stefan Niemann, PhD, Jean-Charles Delvenne, PhD, Michel Delmée, MD, Lufuno Razwiedani, MD, Maphoshane Nchabeleng, MD, Philip Supply, PhD †, Bouke C de Jong, MD †, Emmanuel André, MD  †

Published: October 17, 2018 / DOI: https://doi.org/10.1016/S1473-3099(18)30496-1




Global roll-out of rapid molecular assays is revolutionising the diagnosis of rifampicin resistance, predictive of multidrug-resistance, in tuberculosis. However, 30% of the multidrug-resistant (MDR) strains in an eSwatini study harboured the Ile491Phe mutation in the rpoB gene, which is associated with poor rifampicin-based treatment outcomes but is missed by commercial molecular assays or scored as susceptible by phenotypic drug-susceptibility testing deployed in South Africa. We evaluated the presence of Ile491Phe among South African tuberculosis isolates reported as isoniazid-monoresistant according to current national testing algorithms.


We screened records of 37 644 Mycobacterium tuberculosis positive cultures from four South African provinces, diagnosed at the National Health Laboratory Service–Dr George Mukhari Tertiary Laboratory, to identify isolates with rifampicin sensitivity and isoniazid resistance according to Xpert MTB/RIF, GenoType MTBDRplus, and BACTEC MGIT 960. Of 1823 isolates that met these criteria, 277 were randomly selected and screened for Ile491Phe with multiplex allele-specific PCR and Sanger sequencing of rpoB. Ile491Phe-positive strains (as well as 17 Ile491Phe-bearing isolates from the eSwatini study) were then tested by Deeplex-MycTB deep sequencing and whole-genome sequencing to evaluate their patterns of extensive resistance, transmission, and evolution.


Ile491Phe was identified in 37 (15%) of 249 samples with valid multiplex allele-specific PCR and sequencing results, thus reclassifying them as MDR. All 37 isolates were additionally identified as genotypically resistant to all first-line drugs by Deeplex-MycTB. Six of the South African isolates harboured four distinct mutations potentially associated with decreased bedaquiline sensitivity. Consistent with Deeplex-MycTB genotypic profiles, whole-genome sequencing revealed concurrent silent spread in South Africa of a MDR tuberculosis strain lineage extending from the eSwatini outbreak and at least another independently emerged Ile491Phe-bearing lineage. Whole-genome sequencing further suggested acquisition of mechanisms compensating for the Ile491Phe fitness cost, and of additional bedaquiline resistance following the introduction of this drug in South Africa.


A substantial number of MDR tuberculosis cases harbouring the Ile491Phe mutation in the rpoB gene in South Africa are missed by current diagnostic strategies, resulting in ineffective first-line treatment, continued amplification of drug resistance, and concurrent silent spread in the community.


VLIR-UOS, National Research Foundation (South Africa), and INNOVIRIS.

Keywords: Antibiotics; Drugs Resistance; Tuberculosis; South Africa.


#Candida auris in South Africa [#ZA], 2012–2016 (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 24, Number 11—November 2018 / Research

Candida auris in South Africa, 2012–2016

Nelesh P. Govender  , Rindidzani E. Magobo, Ruth Mpembe, Mabatho Mhlanga, Phelly Matlapeng, Craig Corcoran, Chetna Govind, Warren Lowman, Marthinus Senekal, and Juno Thomas

Author affiliations: National Health Laboratory Service, Johannesburg, South Africa (N.P. Govender, R.E. Magobo, R. Mpembe, M. Mhlanga, P. Matlapeng, J. Thomas); University of the Witwatersrand, Johannesburg (N.P. Govender, R.E. Magobo, W. Lowman); Ampath Laboratories, Pretoria, South Africa (C. Corcoran); Lancet Laboratories, Durban, South Africa (C. Govind); Vermaak and Partners Pathologists, Johannesburg/Cape Town, South Africa (W. Lowman, M. Senekal)



To determine the epidemiology of Candida auris in South Africa, we reviewed data from public- and private-sector diagnostic laboratories that reported confirmed and probable cases of invasive disease and colonization for October 2012–November 2016. We defined a case as a first isolation of C. auris from any specimen from a person of any age admitted to any healthcare facility in South Africa. We defined probable cases as cases where the diagnostic laboratory had used a nonconfirmatory biochemical identification method and C. haemulonii was cultured. We analyzed 1,692 cases; 93% were from private-sector healthcare facilities, and 92% of cases from known locations were from Gauteng Province. Of cases with available data, 29% were invasive infections. The number of cases increased from 18 (October 2012–November 2013) to 861 (October 2015–November 2016). Our results show a large increase in C. auris cases during the study period, centered on private hospitals in Gauteng Province.

Keywords: Candida auris; Nosocomial Outbreaks; South Africa.


#Replacement of #NAIs susceptible #influenza A(#H1N1) with #resistant phenotype in 2008 and circulation of susceptible influenza A and B viruses during 2009-2013, #ZA (Influenza Other Respir Viruses, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Influenza Other Respir Viruses. 2018 Sep 14. doi: 10.1111/irv.12611. [Epub ahead of print]

Replacement of neuraminidase inhibitor susceptible influenza A(H1N1) with resistant phenotype in 2008 and circulation of susceptible influenza A and B viruses during 2009-2013, South Africa.

Treurnicht FK1, Buys A1, Tempia S2,3, Seleka M1, Cohen AL2,4, Walaza S1,5, Glass AJ6, Rossouw I7, McAnerney J1, Blumberg L8,5, Cohen C1,5, Venter M9,10.

Author information:  1 Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa. 2 Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, USA. 3 Influenza Program, Centers for Disease Control and Prevention, Pretoria, South Africa. 4 Global Immunization Monitoring and Surveillance, Expanded Programme on Immunization, Department of Immunization, Vaccines and Biologicals, World Health Organization, Geneva, Switzerland. 5 School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. 6 Department of Molecular Pathology, Lancet Laboratories, Johannesburg, South Africa. 7 PathCare Laboratories, PathCare Park, N1 City, Cape Town, South Africa. 8 Division of Public Health Surveillance and Response, National Institute of Communicable Diseases, Sandringham, Johannesburg, South Africa. 9 Emerging Arbo-and Respiratory virus Program, Department of Medical Virology, University of Pretoria, Pretoria, South Africa. 10 Tshwane Academic Division, National Health Laboratory Service, Pretoria, South Africa.




Data on the susceptibility of influenza viruses from South Africa to neuraminidase inhibitors (NAIs) is scarce, and no extensive analysis was done.


We aimed to determine oseltamivir and zanamivir susceptibility of influenza A and B virus neuraminidases (NAs), 2007-2013, South Africa.


We enrolled participants through national influenza-like illness surveillance, 2007-2013. Influenza diagnosis was by virus isolation and real-time polymerase chain reaction (qPCR). Drug susceptibility was determined by chemilluminescence-based NA-STAR/NA-XTD assay. Sanger sequencing was used to determine molecular markers of NAI resistance.


Forty percent (6,341/15,985) of participants were positive for influenza viruses using virus isolation (2007-2009) and qPCR (2009-2013) methods. 1,236/6,341 (19.5%) virus isolates were generated of which 307/1,236 (25%) were tested for drug susceptibility. During 2007-2008 the median 50% inhibitory concentration (IC50 ) of oseltamivir for seasonal influenza A(H1N1) increased from of 0.08 nM (range 0.01-3.60) in 2007 to 73 nM (range 1.56-305 nM) in 2008. Influenza A isolates from 2009-2013 were susceptible to oseltamivir [A(H3N2) median IC50 = 0.05 nM (range 0.01-0.08); A(H1N1)pdm09= 0.11 nM (range 0.01-0.78)] and zanamivir [A(H3N2) median IC50 = 0.56 nM (range 0.47-0.66); A(H1N1)pdm09= 0.35 nM (range 0.27-0.533)]. Influenza B viruses were susceptible to both NAIs. NAI resistance-associated substitutions H275Y, E119V, and R150K (N1 numbering) were not detected in influenza A viruses that circulated in 2009-2013.


We confirm replacement of NAI susceptible by resistant phenotype influenza A(H1N1) in 2008. Influenza A and B viruses (2009-2013) remained susceptible to NAIs; therefore these drugs are useful for treating influenza-infected patients.

This article is protected by copyright. All rights reserved.

KEYWORDS: South Africa; influenza; oseltamivir; susceptibility

PMID: 30218485 DOI: 10.1111/irv.12611

Keywords: Seasonal Influenza; H1N1; H1N1pdm09; H3N2; Influenza B; Antivirals; Drugs Resistance; South Africa; Oseltamivir.