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


RESULTS
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.


CONCLUSIONS
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.
von Gottberg
Anne
A
National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa. annev@nicd.ac.za
Klugman
Keith P
KP
Cohen
Cheryl
C
Wolter
Nicole
N
de Gouveia
Linda
L
du Plessis
Mignon
M
Mpembe
Ruth
R
Quan
Vanessa
V
Whitelaw
Andrew
A
Hoffmann
Rena
R
Govender
Nelesh
N
Meiring
Susan
S
Smith
Anthony M
AM
Schrag
Stephanie
S
D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000995:Antitubercular Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003428:Cross Infection; D003430:Cross-Sectional Studies; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D005260:Female; D006801:Humans; D007223:Infant; D064704:Levofloxacin; D008297:Male; D015242:Ofloxacin / Q000627:therapeutic use*; D011008:Pneumococcal Infections / Q000188:drug therapy* / Q000453:epidemiology; D011159:Population Surveillance; D012293:Rifampin / Q000627:therapeutic use; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology; D018709:Statistics, Nonparametric; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000472:pathogenicity; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*; D014944:World Health Organization
D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D064704:Levofloxacin; D015242:Ofloxacin; D012293:Rifampin