Emergence of levofloxacin-non-susceptible Streptococcus pneumoniae and treatment for multidrug-resistant tuberculosis in children in South Africa: a cohort observational surveillance study

Summary Background Use of fluoroquinolones to treat paediatric cases of multidrug-resistant tuberculosis could affect the emergence of resistance to this class of drugs. Our aim was to estimate the incidence of, and risk factors for, invasive pneumococcal disease caused by fluoroquinolone-resistant...

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Published inThe Lancet (British edition) Vol. 371; no. 9618; pp. 1108 - 1113
Main Authors von Gottberg, Anne, FCPath [SA] Micro, Klugman, Keith P, Prof, Cohen, Cheryl, FCPath [SA] Micro, Wolter, Nicole, PhD, de Gouveia, Linda, MT, du Plessis, Mignon, PhD, Mpembe, Ruth, MT, Quan, Vanessa, MBBCh, Whitelaw, Andrew, FCPath [SA] Micro, Hoffmann, Rena, MMed, Govender, Nelesh, FCPath [SA] Micro, Meiring, Susan, MBChB, Smith, Anthony M, PhD, Schrag, Stephanie, DPhil
Format Journal Article
LanguageEnglish
Published England Elsevier Ltd 29.03.2008
Elsevier Limited
Subjects
Adolescent
Anti-Bacterial Agents - therapeutic use
Antitubercular Agents - therapeutic use
Child
Child, Preschool
Children & youth
Cross Infection
Cross-Sectional Studies
Diagnostic tests
Drug resistance
Drug Resistance, Bacterial - drug effects
Female
Hospitals
Humans
Infant
Infections
Internal Medicine
Laboratories
Levofloxacin
Male
Mycobacterium
Nosocomial infection
Ofloxacin - therapeutic use
Patients
Pneumococcal Infections - drug therapy
Pneumococcal Infections - epidemiology
Pneumonia
Population Surveillance
Rifampin - therapeutic use
Risk Factors
South Africa - epidemiology
Statistics, Nonparametric
Streptococcus infections
Streptococcus pneumoniae
Streptococcus pneumoniae - drug effects
Streptococcus pneumoniae - pathogenicity
Tuberculosis
Tuberculosis, Multidrug-Resistant - drug therapy
World Health Organization
South Africa
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Abstract Summary Background Use of fluoroquinolones to treat paediatric cases of multidrug-resistant tuberculosis could affect the emergence of resistance to this class of drugs. Our aim was to estimate the incidence of, and risk factors for, invasive pneumococcal disease caused by fluoroquinolone-resistant Streptococcus pneumoniae in children in South Africa. Methods 21 521 cases of invasive pneumococcal disease were identified by active national surveillance between 2000 and 2006, with enhanced surveillance at 15 sentinel hospitals in seven provinces introduced in 2003. We screened 19 404 isolates (90% of cases) for ofloxacin resistance and measured levofloxacin minimum inhibitory concentrations (MICs) for all isolates that were ofloxacin resistant. Non-susceptibility to levofloxacin was defined as an MIC of 4 mg/L or more. Nasopharyngeal pneumococcal carriage was assessed in 65 children in two tuberculosis hospitals where invasive pneumococcal disease caused by levofloxacin-non-susceptible S pneumoniae had been detected. Findings 12 cases of invasive pneumococcal disease were identified as being non-susceptible to levofloxacin, all in children aged under 15 years. All isolates were rifampicin resistant. Outcome was known for 11 of these patients; five (45%) died. Invasive disease caused by levofloxacin-non-susceptible S pneumoniae was associated with a history of tuberculosis treatment (eight [89%] of nine children with non-susceptible isolates had a history of treatment vs 396 [18%] of 2202 children with susceptible isolates; relative risk [RR] 35·78, 95% CI 4·49–285·30) and nosocomial invasive pneumococcal disease (eight [80%] of ten children with non-susceptible isolates had acquired infection nosocomially vs 109 [4%] of 2709 with susceptible isolates; RR 88·96, 19·10–414·29). 31 (89%) of 35 pneumococcal carriers had bacteria that were non-susceptible to levofloxacin. Interpretation Our data suggest that the use of fluoroquinolones to treat multidrug-resistant tuberculosis in children has led to the emergence of invasive pneumococcal disease caused by levofloxacin-non-susceptible S pneumoniae and its nosocomial spread. Funding National Institute for Communicable Diseases of the National Health Laboratory Service (South Africa), US Agency for International Development Antimicrobial Resistance Initiative, US Centers for Disease Control and Prevention.
AbstractList Use of fluoroquinolones to treat paediatric cases of multidrug-resistant tuberculosis could affect the emergence of resistance to this class of drugs. Our aim was to estimate the incidence of, and risk factors for, invasive pneumococcal disease caused by fluoroquinolone-resistant Streptococcus pneumoniae in children in South Africa. 21521 cases of invasive pneumococcal disease were identified by active national surveillance between 2000 and 2006, with enhanced surveillance at 15 sentinel hospitals in seven provinces introduced in 2003. We screened 19404 isolates (90% of cases) for ofloxacin resistance and measured levofloxacin minimum inhibitory concentrations (MICs) for all isolates that were ofloxacin resistant. Non-susceptibility to levofloxacin was defined as an MIC of 4 mg/L or more. Nasopharyngeal pneumococcal carriage was assessed in 65 children in two tuberculosis hospitals where invasive pneumococcal disease caused by levofloxacin-non-susceptible S pneumoniae had been detected. 12 cases of invasive pneumococcal disease were identified as being non-susceptible to levofloxacin, all in children aged under 15 years. All isolates were rifampicin resistant. Outcome was known for 11 of these patients; five (45%) died. Invasive disease caused by levofloxacin-non-susceptible S pneumoniae was associated with a history of tuberculosis treatment (eight [89%] of nine children with non-susceptible isolates had a history of treatment vs 396 [18%] of 2202 children with susceptible isolates; relative risk [RR] 35.78, 95% CI 4.49-285.30) and nosocomial invasive pneumococcal disease (eight [80%] of ten children with non-susceptible isolates had acquired infection nosocomially vs 109 [4%] of 2709 with susceptible isolates; RR 88.96, 19.10-414.29). 31 (89%) of 35 pneumococcal carriers had bacteria that were non-susceptible to levofloxacin. Our data suggest that the use of fluoroquinolones to treat multidrug-resistant tuberculosis in children has led to the emergence of invasive pneumococcal disease caused by levofloxacin-non-susceptible S pneumoniae and its nosocomial spread.
Use of fluoroquinolones to treat paediatric cases of multidrug-resistant tuberculosis could affect the emergence of resistance to this class of drugs. Our aim was to estimate the incidence of, and risk factors for, invasive pneumococcal disease caused by fluoroquinolone-resistant Streptococcus pneumoniae in children in South Africa. 21 521 cases of invasive pneumococcal disease were identified by active national surveillance between 2000 and 2006, with enhanced surveillance at 15 sentinel hospitals in seven provinces introduced in 2003. We screened 19 404 isolates (90% of cases) for ofloxacin resistance and measured levofloxacin minimum inhibitory concentrations (MICs) for all isolates that were ofloxacin resistant. Non-susceptibility to levofloxacin was defined as an MIC of 4 mg/L or more. Nasopharyngeal pneumococcal carriage was assessed in 65 children in two tuberculosis hospitals where invasive pneumococcal disease caused by levofloxacin-non-susceptible S pneumoniae had been detected. 12 cases of invasive pneumococcal disease were identified as being non-susceptible to levofloxacin, all in children aged under 15 years. All isolates were rifampicin resistant. Outcome was known for 11 of these patients; five (45%) died. Invasive disease caused by levofloxacin-non-susceptible S pneumoniae was associated with a history of tuberculosis treatment (eight [89%] of nine children with non-susceptible isolates had a history of treatment vs 396 [18%] of 2202 children with susceptible isolates; relative risk [RR] 35·78, 95% CI 4·49–285·30) and nosocomial invasive pneumococcal disease (eight [80%] of ten children with non-susceptible isolates had acquired infection nosocomially vs 109 [4%] of 2709 with susceptible isolates; RR 88·96, 19·10–414·29). 31 (89%) of 35 pneumococcal carriers had bacteria that were non-susceptible to levofloxacin. Our data suggest that the use of fluoroquinolones to treat multidrug-resistant tuberculosis in children has led to the emergence of invasive pneumococcal disease caused by levofloxacin-non-susceptible S pneumoniae and its nosocomial spread. National Institute for Communicable Diseases of the National Health Laboratory Service (South Africa), US Agency for International Development Antimicrobial Resistance Initiative, US Centers for Disease Control and Prevention.
Use of fluoroquinolones to treat paediatric cases of multidrug-resistant tuberculosis could affect the emergence of resistance to this class of drugs. Our aim was to estimate the incidence of, and risk factors for, invasive pneumococcal disease caused by fluoroquinolone-resistant Streptococcus pneumoniae in children in South Africa. 21,521 cases of invasive pneumococcal disease were identified by active national surveillance between 2000 and 2006, with enhanced surveillance at 15 sentinel hospitals in seven provinces introduced in 2003. We screened 19,404 isolates (90% of cases) for ofloxacin resistance and measured levofloxacin minimum inhibitory concentrations (MICs) for all isolates that were ofloxacin resistant. Non-susceptibility to levofloxacin was defined as an MIC of 4 mg/L or more. Nasopharyngeal pneumococcal carriage was assessed in 65 children in two tuberculosis hospitals where invasive pneumococcal disease caused by levofloxacin-non-susceptible S pneumoniae had been detected. 12 cases of invasive pneumococcal disease were identified as being non-susceptible to levofloxacin, all in children aged under 15 years. All isolates were rifampicin resistant. Outcome was known for 11 of these patients; five (45%) died. Invasive disease caused by levofloxacin-non-susceptible S pneumoniae was associated with a history of tuberculosis treatment (eight [89%] of nine children with non-susceptible isolates had a history of treatment vs 396 [18%] of 2202 children with susceptible isolates; relative risk [RR] 35.78, 95% CI 4.49-285.30) and nosocomial invasive pneumococcal disease (eight [80%] of ten children with non-susceptible isolates had acquired infection nosocomially vs 109 [4%] of 2709 with susceptible isolates; RR 88.96, 19.10-414.29). 31 (89%) of 35 pneumococcal carriers had bacteria that were non-susceptible to levofloxacin. Our data suggest that the use of fluoroquinolones to treat multidrug-resistant tuberculosis in children has led to the emergence of invasive pneumococcal disease caused by levofloxacin-non-susceptible S pneumoniae and its nosocomial spread.
Summary Background Use of fluoroquinolones to treat paediatric cases of multidrug-resistant tuberculosis could affect the emergence of resistance to this class of drugs. Our aim was to estimate the incidence of, and risk factors for, invasive pneumococcal disease caused by fluoroquinolone-resistant Streptococcus pneumoniae in children in South Africa. Methods 21 521 cases of invasive pneumococcal disease were identified by active national surveillance between 2000 and 2006, with enhanced surveillance at 15 sentinel hospitals in seven provinces introduced in 2003. We screened 19 404 isolates (90% of cases) for ofloxacin resistance and measured levofloxacin minimum inhibitory concentrations (MICs) for all isolates that were ofloxacin resistant. Non-susceptibility to levofloxacin was defined as an MIC of 4 mg/L or more. Nasopharyngeal pneumococcal carriage was assessed in 65 children in two tuberculosis hospitals where invasive pneumococcal disease caused by levofloxacin-non-susceptible S pneumoniae had been detected. Findings 12 cases of invasive pneumococcal disease were identified as being non-susceptible to levofloxacin, all in children aged under 15 years. All isolates were rifampicin resistant. Outcome was known for 11 of these patients; five (45%) died. Invasive disease caused by levofloxacin-non-susceptible S pneumoniae was associated with a history of tuberculosis treatment (eight [89%] of nine children with non-susceptible isolates had a history of treatment vs 396 [18%] of 2202 children with susceptible isolates; relative risk [RR] 35·78, 95% CI 4·49–285·30) and nosocomial invasive pneumococcal disease (eight [80%] of ten children with non-susceptible isolates had acquired infection nosocomially vs 109 [4%] of 2709 with susceptible isolates; RR 88·96, 19·10–414·29). 31 (89%) of 35 pneumococcal carriers had bacteria that were non-susceptible to levofloxacin. Interpretation Our data suggest that the use of fluoroquinolones to treat multidrug-resistant tuberculosis in children has led to the emergence of invasive pneumococcal disease caused by levofloxacin-non-susceptible S pneumoniae and its nosocomial spread. Funding National Institute for Communicable Diseases of the National Health Laboratory Service (South Africa), US Agency for International Development Antimicrobial Resistance Initiative, US Centers for Disease Control and Prevention.
Background Use of fluoroquinolones to treat paediatric cases of multidrug-resistant tuberculosis could affect the emergence of resistance to this class of drugs. Our aim was to estimate the incidence of, and risk factors for, invasive pneumococcal disease caused by fluoroquinolone-resistant Streptococcus pneumoniae in children in South Africa. Methods 21521 cases of invasive pneumococcal disease were identified by active national surveillance between 2000 and 2006, with enhanced surveillance at 15 sentinel hospitals in seven provinces introduced in 2003. We screened 19 404 isolates (90% of cases) for ofloxacin resistance and measured levofloxacin minimum inhibitory concentrations (MICs) for all isolates that were ofloxacin resistant. Non-susceptibility to levofloxacin was defined as an MIC of 4 mg/L or more. Nasopharyngeal pneumococcal carriage was assessed in 65 children in two tuberculosis hospitals where invasive pneumococcal disease caused by levofloxacin-non-susceptible S pneumoniae had been detected. Findings 12 cases of invasive pneumococcal disease were identified as being non-susceptible to levofloxacin, all in children aged under 15 years. All isolates were rifampicin resistant Outcome was known for 11 of these patients; five (45%) died. Invasive disease caused by levofloxacin-non-susceptible S pneumoniae was associated with a history of tuberculosis treatment (eight [89%] of nine children with non-susceptible isolates had a history of treatment vs 396 [18%] of 2202 children with susceptible isolates; relative risk [RR] 35; 78, 95% CI 4; 49-285; 30) and nosocomial invasive pneumococcal disease (eight [80%] of ten children with non-susceptible isolates had acquired infection nosocomially vs 109 [4%] of 2709 with susceptible isolates; RR 88; 96, 19; 10-414; 29). 31 (89%) of 35 pneumococcal carriers had bacteria that were non-susceptible to levofloxacin. Interpretation Our data suggest that the use of fluoroquinolones to treat multidrug-resistant tuberculosis in children has led to the emergence of invasive pneumococcal disease caused by levofloxarin-non-susceptible S pneumoniae and its nosocomial spread. Funding National Institute for Communicable Diseases of the National Health Laboratory Service (South Africa), US Agency for International Development Antimicrobial Resistance Initiative, US Centers for Disease Control and Prevention.
BACKGROUNDUse of fluoroquinolones to treat paediatric cases of multidrug-resistant tuberculosis could affect the emergence of resistance to this class of drugs. Our aim was to estimate the incidence of, and risk factors for, invasive pneumococcal disease caused by fluoroquinolone-resistant Streptococcus pneumoniae in children in South Africa.METHODS21,521 cases of invasive pneumococcal disease were identified by active national surveillance between 2000 and 2006, with enhanced surveillance at 15 sentinel hospitals in seven provinces introduced in 2003. We screened 19,404 isolates (90% of cases) for ofloxacin resistance and measured levofloxacin minimum inhibitory concentrations (MICs) for all isolates that were ofloxacin resistant. Non-susceptibility to levofloxacin was defined as an MIC of 4 mg/L or more. Nasopharyngeal pneumococcal carriage was assessed in 65 children in two tuberculosis hospitals where invasive pneumococcal disease caused by levofloxacin-non-susceptible S pneumoniae had been detected.FINDINGS12 cases of invasive pneumococcal disease were identified as being non-susceptible to levofloxacin, all in children aged under 15 years. All isolates were rifampicin resistant. Outcome was known for 11 of these patients; five (45%) died. Invasive disease caused by levofloxacin-non-susceptible S pneumoniae was associated with a history of tuberculosis treatment (eight [89%] of nine children with non-susceptible isolates had a history of treatment vs 396 [18%] of 2202 children with susceptible isolates; relative risk [RR] 35.78, 95% CI 4.49-285.30) and nosocomial invasive pneumococcal disease (eight [80%] of ten children with non-susceptible isolates had acquired infection nosocomially vs 109 [4%] of 2709 with susceptible isolates; RR 88.96, 19.10-414.29). 31 (89%) of 35 pneumococcal carriers had bacteria that were non-susceptible to levofloxacin.INTERPRETATIONOur data suggest that the use of fluoroquinolones to treat multidrug-resistant tuberculosis in children has led to the emergence of invasive pneumococcal disease caused by levofloxacin-non-susceptible S pneumoniae and its nosocomial spread.
Author Quan, Vanessa, MBBCh
Wolter, Nicole, PhD
Hoffmann, Rena, MMed
Meiring, Susan, MBChB
Klugman, Keith P, Prof
Cohen, Cheryl, FCPath [SA] Micro
de Gouveia, Linda, MT
Govender, Nelesh, FCPath [SA] Micro
von Gottberg, Anne, FCPath [SA] Micro
Schrag, Stephanie, DPhil
Smith, Anthony M, PhD
du Plessis, Mignon, PhD
Whitelaw, Andrew, FCPath [SA] Micro
Mpembe, Ruth, MT
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/18359074$$D View this record in MEDLINE/PubMed
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Govender, Nelesh
Ahmed, Khatija
Hoffmann, Rena
Vanmali, Trusha
Karstaedt, Alan
Wadula, Jeannette
Vasaikar, Sandeep
Prentice, Elizabeth
Meiring, Susan
Simpson, John
Whitelaw, Andrew
Pretorius, Anne-Marie
Bauer, Keith
Lindeque, Kathy
Brink, Adrian
Cohen, Cheryl
Senekal, Marthinus
Ngwira, Donald
Keddy, Karen
Möller, André
Heney, Claire
von Gottberg, Anne
Sein, Pyu Pyu
Lekalakala, Ruth
Roditi, Denise
Feldman, Charles
Cheyip, Mireille
Weldhagen, Gerhard
Quan, Vanessa
Bhola, Prathna
Mutanda, Charles
Sturm, Wim
Liebowitz, Lynne
Seetharam, Sharona
Lebudi, Jacob
Wasserman, Elizabeth
de Gouveia, Linda
Hoyland, Greta
Perovic, Olga
Smith, Peter
Hoosen, Anwar
Dove, Mike
Frean, John
van Rensberg, Nolan Janse
Sithole, Sindiswe
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Snippet Summary Background Use of fluoroquinolones to treat paediatric cases of multidrug-resistant tuberculosis could affect the emergence of resistance to this class...
Use of fluoroquinolones to treat paediatric cases of multidrug-resistant tuberculosis could affect the emergence of resistance to this class of drugs. Our aim...
Background Use of fluoroquinolones to treat paediatric cases of multidrug-resistant tuberculosis could affect the emergence of resistance to this class of...
BACKGROUNDUse of fluoroquinolones to treat paediatric cases of multidrug-resistant tuberculosis could affect the emergence of resistance to this class of...
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StartPage 1108
SubjectTerms Adolescent
Anti-Bacterial Agents - therapeutic use
Antitubercular Agents - therapeutic use
Child
Child, Preschool
Children & youth
Cross Infection
Cross-Sectional Studies
Diagnostic tests
Drug resistance
Drug Resistance, Bacterial - drug effects
Female
Hospitals
Humans
Infant
Infections
Internal Medicine
Laboratories
Levofloxacin
Male
Mycobacterium
Nosocomial infection
Ofloxacin - therapeutic use
Patients
Pneumococcal Infections - drug therapy
Pneumococcal Infections - epidemiology
Pneumonia
Population Surveillance
Rifampin - therapeutic use
Risk Factors
South Africa - epidemiology
Statistics, Nonparametric
Streptococcus infections
Streptococcus pneumoniae
Streptococcus pneumoniae - drug effects
Streptococcus pneumoniae - pathogenicity
Tuberculosis
Tuberculosis, Multidrug-Resistant - drug therapy
World Health Organization
Title Emergence of levofloxacin-non-susceptible Streptococcus pneumoniae and treatment for multidrug-resistant tuberculosis in children in South Africa: a cohort observational surveillance study
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https://dx.doi.org/10.1016/S0140-6736(08)60350-5
https://www.ncbi.nlm.nih.gov/pubmed/18359074
https://www.proquest.com/docview/199001990
https://search.proquest.com/docview/20881366
https://search.proquest.com/docview/70447590
Volume 371
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