title: The Emergence of Reduced Ciprofloxacin Susceptibility in Salmonella enterica Causing Bloodstream Infections in Rural Ghana.
abstract: BACKGROUND
  Salmonella ranks among the leading causes of bloodstream infections in sub-Saharan Africa. Multidrug resistant typhoidal and nontyphoidal Salmonella (NTS) isolates have been previously identified in this region. However, resistance to ciprofloxacin has rarely been reported in West Africa. This study aims to assess susceptibility against ciprofloxacin in Salmonella causing invasive bloodstream infections among children in rural Ghana.
  
  
  METHODS
  From May 2007 until May 2012, children attending a rural district hospital in central Ghana were eligible for recruitment. Salmonella enterica isolated from blood cultures were assessed for ciprofloxacin susceptibility by Etest (susceptible minimum inhibitory concentration [MIC] ≤ 0.06 µg/mL). The gyrA, gyrB, parC, and parE genes were sequenced to identify mutations associated with changes in susceptibility to fluoroquinolones.
  
  
  RESULTS
  Two hundred eighty-five Salmonella enterica isolates from 5211 blood cultures were most commonly identified as Salmonella enterica serovar Typhimurium (n = 129 [45%]), Salmonella enterica serovar Typhi (n = 89 [31%]), Salmonella enterica serovar Dublin (n = 20 [7%]), and Salmonella enterica serovar Enteritidis (n = 19 [7%]). All S. Typhi and S. Dublin were susceptible to ciprofloxacin. Reduced susceptibility (MIC >0.06 µg/mL) was found in 53% (10/19) of S. Enteritidis and in 2% (3/129) of S. Typhimurium isolates. Sequencing detected a single gyrB mutation (Glu466Asp) and a single gyrA mutation (Ser83Tyr) in all 3 S. Typhimurium isolates, while 9 of 10 S. Enteritidis harbored single gyrA mutations (Asp87Gly, Asp87Asn, or Asp87Tyr). No mutations were found in the parC and parE genes.
  
  
  CONCLUSIONS
  Ciprofloxacin susceptibility in invasive NTS in rural Ghana is highly dependent on serotype. Although reduced ciprofloxacin susceptibility is low in S. Typhimurium, more than half of all S. Enteritidis isolates are affected. Healthcare practitioners in Ghana should be aware of potential treatment failure in patients with invasive S. Enteritidis infections.
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine German Center for Infection Research, and Hamburg-Borstel-Lübeck, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Eibach
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine German Center for Infection Research, and Hamburg-Borstel-Lübeck, Germany.
authors.forename: Hassan M
authors.initials: HM
authors.lastname: Al-Emran
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine German Center for Infection Research, and Hamburg-Borstel-Lübeck, Germany.
authors.forename: Denise Myriam
authors.initials: DM
authors.lastname: Dekker
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine German Center for Infection Research, and Hamburg-Borstel-Lübeck, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Krumkamp
authors.affiliation: Kumasi Centre for Collaborative Research in Tropical Medicine, Ghana.
authors.forename: Yaw
authors.initials: Y
authors.lastname: Adu-Sarkodie
authors.affiliation: International Vaccine Institute, Seoul, Republic of Korea.
authors.forename: Ligia Maria
authors.initials: LM
authors.lastname: Cruz Espinoza
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine.
authors.forename: Christa
authors.initials: C
authors.lastname: Ehmen
authors.affiliation: Kumasi Centre for Collaborative Research in Tropical Medicine, Ghana.
authors.forename: Kennedy
authors.initials: K
authors.lastname: Boahen
authors.affiliation: Institute of Biochemistry and Molecular Biology, University of Hamburg.
authors.forename: Peter
authors.initials: P
authors.lastname: Heisig
authors.affiliation: International Vaccine Institute, Seoul, Republic of Korea.
authors.forename: Justin
authors.initials: J
authors.lastname: Im
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine.
authors.forename: Anna
authors.initials: A
authors.lastname: Jaeger
authors.affiliation: International Vaccine Institute, Seoul, Republic of Korea.
authors.forename: Vera
authors.initials: V
authors.lastname: von Kalckreuth
authors.affiliation: International Vaccine Institute, Seoul, Republic of Korea.
authors.forename: Gi Deok
authors.initials: GD
authors.lastname: Pak
authors.affiliation: International Vaccine Institute, Seoul, Republic of Korea.
authors.forename: Ursula
authors.initials: U
authors.lastname: Panzner
authors.affiliation: International Vaccine Institute, Seoul, Republic of Korea.
authors.forename: Se Eun
authors.initials: SE
authors.lastname: Park
authors.affiliation: Institute of Biochemistry and Molecular Biology, University of Hamburg.
authors.forename: Alexander
authors.initials: A
authors.lastname: Reinhardt
authors.affiliation: Kumasi Centre for Collaborative Research in Tropical Medicine, Ghana.
authors.forename: Nimako
authors.initials: N
authors.lastname: Sarpong
authors.affiliation: International Vaccine Institute, Seoul, Republic of Korea Institute of Medical Microbiology, University of Cologne, Germany.
authors.forename: Heidi
authors.initials: H
authors.lastname: Schütt-Gerowitt
authors.affiliation: International Vaccine Institute, Seoul, Republic of Korea.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Wierzba
authors.affiliation: International Vaccine Institute, Seoul, Republic of Korea.
authors.forename: Florian
authors.initials: F
authors.lastname: Marks
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine German Center for Infection Research, and Hamburg-Borstel-Lübeck, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: May
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016470:Bacteremia / Q000453:epidemiology / Q000382:microbiology*; D002675:Child, Preschool; D002939:Ciprofloxacin / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D005869:Ghana / Q000453:epidemiology; D006801:Humans; D007223:Infant; D008297:Male; D008826:Microbial Sensitivity Tests; D011446:Prospective Studies; D012480:Salmonella Infections / Q000453:epidemiology / Q000382:microbiology*; D019779:Salmonella enterica / Q000187:drug effects* / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D002939:Ciprofloxacin
keywords: Africa; Ghana; Salmonella; multidrug resistant; susceptibility