JAC Advance Access originally published online on December 30, 2005
Journal of Antimicrobial Chemotherapy 2006 57(2):366; doi:10.1093/jac/dki466
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Correspondence |
Invasive Haemophilus influenzae isolates with decreased levofloxacin susceptibility in Hong Kong
1 Centre of Infection and Department of Microbiology, The University of Hong Kong, Hong Kong SAR, China; 2 Department of Clinical Pathology, Princess Margaret Hospital, Hong Kong SAR, China;3 Department of Clinical Pathology, Pamela Youde Hospital, Hong Kong SAR, China
* Corresponding author. Division of Infectious Diseases, Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Pokfulam, Hong Kong SAR, China. Tel: +852-2855-4897; Fax: +852-2855-1241; E-mail: plho{at}hkucc.hku.hk
Keywords: bacteraemia , fluoroquinolones , antimicrobial resistance , H. influenzae , molecular diagnostic techniques
Sir,
Although Haemophilus influenzae with phenotypic resistance to fluoroquinolones remains rare, recent studies suggested that decreased susceptibility due to first-step mutations in gyrA or parC may be more common.1,2 First-step mutants with reduced susceptibility generally remain undetected when fluoroquinolone susceptibility tests are interpreted using current breakpoints. However, it is important to detect first-step mutants because they may be associated with clinical failures and high-level resistance may emerge during treatment with fluoroquinolones.3 In this regard, nalidixic acid has been found to be a useful indicator compound for the detection of quinolone resistance in H. influenzae.4 By using nalidixic acid, we previously reported an incidence of 0.9% for decreased susceptibility to levofloxacin among 563 H. influenzae isolates carried by children.1
In an attempt to define the incidence of decreased susceptibility to levofloxacin among H. influenzae causing invasive infections in Hong Kong, we retrospectively tested all H. influenzae isolated from blood samples of patients admitted to three hospitals during 1998–2003. The three hospitals are estimated to provide an inpatient service for approximately one-quarter of the 6.5 million population in Hong Kong. The MICs of nalidixic acid and levofloxacin were determined by the MIC microbroth dilution method.1 Nalidixic acid resistance was defined as an MIC of 
32 mg/L.1 Quality control strains H. influenzae ATCC 49247 and ATCC 49766 were included with each run. A multiplex PCR procedure was used for capsular typing.5 The subset of isolates with reduced susceptibility to levofloxacin was examined further by multi-locus sequence typing (MLST).6 Previously described primers and methods were used to define mutations in gyrA and parC genes.1
Of 29 invasive isolates three (10.3%) were resistant to nalidixic acid with an MIC of 128 mg/L; the MICs ranged from 0.5 to 4 mg/L for nalidixic acid-susceptible isolates. Levofloxacin MICs for the three nalidixic acid-resistant isolates were 0.06–0.12 mg/L, compared with an MIC range of 0.004–0.0016 mg/L for the nalidixic acid-susceptible isolates. The three nalidixic acid-resistant isolates were non-capsulated. All three patients with infection by nalidixic acid-resistant isolates had underlying disease (Case 1, recurrent pyogenic cholangitis; Case 2, adenocarcinoma of lung; and Case 3, multiple myeloma). Case 3 had a history of exposure to fluoroquinolones (levofloxacin) while the other two did not. The quinolone resistance determining regions of gyrA and parC for the three isolates were sequenced and a Ser-84
Lys substitution was found in GyrA in all three. No substitution was found in ParC. MLST analysis of these three isolates revealed three distinct allelic profiles: 14-44-1-1-22-1-5 (ST183), 1-1-1-1-64-42-5 (ST136) and 1-24-36-14-45-1-5 (a novel ST), indicating that they were not clonally related.
It is noteworthy that fluoroquinolone resistance in Streptococcus pneumoniae is also high in Hong Kong. Since both H. influenzae and S. pneumoniae are often found in the respiratory tract, the two organisms may be subjected to a common antibiotic selection pressure. In this regard, a relationship between resistance in H. influenzae and S. pneumoniae has also been noted by others.7 In conclusion, this study suggests that low-level quinolone resistance in H. influenzae may be an under-recognized phenomenon.
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Acknowledgements
This work was supported by a research grant from the UDF Project-Research Centre of Emerging Infection Diseases.
References
1. Ho PL, Chow KH, Mak GC et al. Decreased levofloxacin susceptibility in Haemophilus influenzae in children, Hong Kong. Emerg Infect Dis 2004; 10: 1960–2.[ISI][Medline]
2. Biedenbach DJ, Jones RN. Five-year analysis of Haemophilus influenzae isolates with reduced susceptibility to fluoroquinolones: prevalence results from the SENTRY antimicrobial surveillance program. Diagn Microbiol Infect Dis 2003; 46: 55–61.[CrossRef][ISI][Medline]
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Vila J, Ruiz J, Sanchez F et al. Increase in quinolone resistance in a Haemophilus influenzae strain isolated from a patient with recurrent respiratory infections treated with ofloxacin. Antimicrob Agents Chemother 1999; 43: 161–2.
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Falla TJ, Crook DW, Brophy LN et al. PCR for capsular typing of Haemophilus influenzae. J Clin Microbiol 1994; 32: 2382–6.
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Meats E, Feil EJ, Stringer S et al. Characterization of encapsulated and noncapsulated Haemophilus influenzae and determination of phylogenetic relationships by multilocus sequence typing. J Clin Microbiol 2003; 41: 1623–36.
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Jones ME, Karlowsky JA, Blosser-Middleton R et al. Relationship between antibiotic resistance in Streptococcus pneumoniae and that in Haemophilus influenzae: evidence for common selective pressure. Antimicrob Agents Chemother 2002; 46: 3106–7.
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