Correspondence Table 1. Antimicrobial susceptibility patterns of the Acinetobacter isolates Antibiotic
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MICs (mg/L) using the agar dilution method Ampicillin >128 Piperacillin >128 Amoxicillin/clavulanate >128 Piperacillin/tazobactam 128 Cefoxitin 128 Cefotaxime 64 Ceftazidime 32 Meropenem 64 Meropenem + EDTA (320 mg/L) 8 Imipenem 128 Imipenem + EDTA (320 mg/L) 16 Nalidixic acid >128 Ciprofloxacin 8 Gentamicin 32 Amikacin 0.5 MICs (mg/L) using the Etest method Meropenem 32 Imipenem (MBL test) 24 Imipenem + EDTA (MBL test) 1 Tigecycline 0.25 Colistin 0.25
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>128 >128 >128 128 >128 32 16 128 32 128 32 >128 4 1 2
3. Donald HM, Scaife W, Amyes SGB et al. Sequence analysis of ARI-1, a novel OXA b-lactamase, responsible for imipenem resistance in Acinetobacter baumannii 6B92. Antimicrob Agents Chemother 2000; 44: 196–9. 4. Turton JF, Ward ME, Woodford N et al. The role of ISAba1 in expression of OXA carbapenemase genes in Acinetobacter baumannii. FEMS Microbiol Lett 2006; 258: 72–7. 5. Traub WH, Bauer D. Surveillance of nosocomial cross-infections due to three Acinetobacter genospecies (Acinetobacter baumannii, genospecies 3 and genospecies 13) during a 10-year observation period: serotyping, macrorestriction analysis of genomic DNA and antibiotic susceptibilities. Chemotherapy 2000; 46: 282–92. 6. Segal H, Elisha BG. Use of Etest MBL strips for the detection of carbapenemases in Acinetobacter baumannii. J Antimicrob Chemother 2005; 56: 598.
Journal of Antimicrobial Chemotherapy doi:10.1093/jac/dkl359 Advance Access publication 2 September 2006
Antibiotic susceptibility of 50 clinical isolates of Burkholderia pseudomallei from Singapore
32 12 1 0.25 0.5
The presence of OXA-23 carbapenemase-producing Acinetobacter spp. in the Irish Republic has not yet been associated with outbreak problems as seen in the UK. Nevertheless, the emergence of such a resistance mechanism in Acinetobacter isolates represents a worrying trend, although it is probably unsurprising given the recent trends in carbapenem resistance elsewhere in the world. We would like to reiterate the importance of prudence in antimicrobial prescription and adherence to infection control measures in the efforts to control the rise of such resistance mechanisms, as well as the urgent need for new antimicrobial agents in the face of pan-b-lactam resistance.
Acknowledgements We would like to thank Dr Susan Brown for the donation of the OXA positive controls and Dr Jane Turton for performing the ARDRA and PFGE on our isolates.
Transparency declarations We have no affiliations with the pharmaceutical industry or any related commercial concerns.
References 1. Afzal-Shah M, Livermore DM. Worldwide emergence of carbapenem-resistant Acinetobacter spp. J Antimicrob Chemother 1998; 41: 576–7. 2. Turton JF, Kaufmann ME, Glover J et al. Detection and typing of integrons in epidemic strains of Acinetobacter baumannii found in the United Kingdom. J Clin Microbiol 2005; 43: 3074–82.
Suppiah Paramalingam Sivalingam*, Siew Hoon Sim, Lay Tin Aw and Eng Eong Ooi Defence Medical & Environmental Research Institute, DSO National Laboratories, 27 Medical Drive, 117510, Singapore Keywords: MICs, melioidosis, prophylaxis, Etest *Corresponding author. Tel: +65-6485-7255; Fax: +65-648-7262; E-mail:
[email protected]
Sir, Burkholderia pseudomallei is the aetiological agent of melioidosis, a potentially fatal disease in humans and animals. In Singapore, a high incidence of melioidosis cases was observed in early 2004 with a high mortality rate (40%).1 Prevention of exposure is difficult as this organism is common in the soil of many parts of south-east Asia. In the absence of a vaccine, antibiotic prophylaxis for those predisposed to melioidosis could be explored. Others have shown that oral doxycycline/ ciprofloxacin could prevent melioidosis in experimentally infected mice.2 We thus examined the in vitro susceptibility of 50 clinical isolates obtained from five local hospitals in Singapore, between the years 1996 and 2004, of which 31 were from the outbreak in 2004,1 to four oral antibiotics, namely amoxicillin/clavulanic acid, doxycycline, ciprofloxacin and co-trimoxazole. MICs were determined by the Etest (AB Biodisk, Solna, Sweden) method using Mueller–Hinton (MHII) agar (Oxoid, Basingstoke, UK) and the plates were read after incubation at 37 C for 24 h. The MIC of each antibiotic (in mg/L) for each B. pseudomallei isolate was reported as susceptible, intermediate or resistant as per CLSI3 guidelines: 8/4, 16/8 and 32/16 for amoxicillin/clavulanic acid, 4, 8 and 16 for doxycycline, 2/38, – and 4/76 for co-trimoxazole and 1, 2 and 4 for ciprofloxacin. E. coli ATCC 25922 and Pseudomonas aeruginosa
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Correspondence ATCC 27853 were used as susceptible controls for each antibiotic. All 50 isolates tested were susceptible to amoxicillin/ clavulanic acid (MIC90 6/3 mg/L; range 2.5/0.125–6/3 mg/L) and doxycycline (MIC90 1.5 mg/L; range 0.19–4 mg/L). For co-trimoxazole (MIC90 4/76 mg/L; range 0.047/0.893–6/114 mg/L), 78% of the isolates were susceptible, 16% were intermediate and 6% were resistant. Overall, 70% of the isolates were susceptible to ciprofloxacin (MIC90 2 mg/L; range 0.064–2 mg/L). Doxycycline and amoxicillin/clavulanic acid have been shown to be effective when used alone for the treatment of localized melioidosis4 or as maintenance therapy following septicaemic melioidosis. The rate of resistance to co-trimoxazole in the present study is lower than that described in Thailand (13%),5 while Ho et al.6 reported lower susceptibility (8.5% of 71 isolates) to ciprofloxacin compared with our findings. The use of fluoroquinolones for treating melioidosis has generally been controversial because of high in vitro MICs for some strains of B. pseudomallei, which exceed levels that can be achieved in serum. However ciprofloxacin is still used in the treatment of melioidosis because it has bactericidal activity, a prolonged postantibiotic effect and has good penetration into phagocytic cells, which might eliminate or inhibit the production of glycocalyx. Our in vitro studies indicate that of the four antibiotics tested doxycycline and amoxicillin/clavulanic acid are the preferred oral prophylaxis to be considered or further explored in our local context.
Acknowledgements We thank HQ Medical Corps of the Singapore Armed Forces for their support in this study.
Transparency declarations We have no conflicts of interest concerning the work reported in this paper.
References 1. Liu Y, Loh JP, Aw LT et al. Rapid molecular typing of Burkholderia pseudomallei, isolated in an outbreak of melioidosis in Singapore in 2004, based on variable-number tandem repeats. Trans R Soc Trop Med Hyg 2006; 100: 687–92. 2. Russell P, Eley SM, Ellis J et al. Comparison of efficacy of ciprofloxacin and doxycycline against experimental melioidosis and glanders. J Antimicrob Chemother 2000; 45: 813–8. 3. National Committee for Clinical Laboratory Standards. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically—Sixth Edition: Approved Standard M7-A6. NCCLS,Wayne, PA, USA, 2003. 4. Leelarasamee A, Bovornkitti S. Melioidosis: review and update. Rev Infect Dis 1989; 11: 413–25. 5. Vanaporn W, Cheng AC, Wirongrong C et al. Trimethoprim/ sulfamethxazole resistance in clinical isolates of Burkholderia pseudomallei. J Antimicrob Chemother 2005; 55: 1029–31. 6. Ho PL, Cheung TKM, Kinoshita R et al. Activity of five fluoroquinolones against 71 isolates of Burkholderia pseudomallei. J Antimicrob Chemother 2002; 49: 1039–46.
Journal of Antimicrobial Chemotherapy doi:10.1093/jac/dkl346 Advance Access publication 18 August 2006
Emergence of a Helicobacter pylori isolate with reduced susceptibility to tetracycline in Germany Erik Glocker* and Manfred Kist National Reference Centre for Helicobacter pylori, Department of Microbiology and Hygiene, Institute of Medical Microbiology and Hygiene, University Hospital Freiburg, Hermann-Herder-Strasse 11, 79104 Freiburg, Germany Keywords: surveillance, antimicrobial resistance, treatment failures, H. pylori *Corresponding author. Tel: +49-761-203-6539; Fax: +49-761203-6562; E-mail:
[email protected]
Sir, Helicobacter pylori persists lifelong in infected individuals and is associated with the development of peptic ulcer diseases, MALT-lymphoma or gastric cancer.1 Antimicrobial therapy, usually including two antibiotics and a proton pump inhibitor, is recommended to eradicate the bacteria. However, increasing resistances to first-line antibiotic drugs such as clarithromycin impair successful eradication of H. pylori and result in therapy failures.2 Tetracyclines, included in quadruple eradication regimens, were shown to be effective in such cases. So far, tetracycline-resistant H. pylori isolates have been extremely rare, particularly in Europe.3 Here, we report the first detection of an H. pylori strain with reduced susceptibility to tetracycline in Germany. The strain was isolated from a multimorbid 70-yearold woman suffering from antrum gastritis, chronic obstructive pulmonary disease, hypothyroidism, arthrosis and adult-onset diabetes mellitus. Between 2000 and 2005, due to relapsing bacterial lung infections, repeated antibiotic treatments including cefuroxime, ciprofloxacin, roxithromycin, levofloxacin and doxycycline were applied. In March 2005, her gastroenterologist diagnosed an H. pylori-positive antrum gastritis. As first-line eradication, a triple therapy consisting of amoxicillin (1 g, twice daily), clarithromycin (500 mg, twice daily) and a proton pump inhibitor (standard dose, twice daily) was administered. In November 2005, the still existing H. pylori-positive antrum gastritis prompted the physician to prescribe a therapy including clarithromycin (500 mg, twice daily), metronidazole (500 mg, twice daily) and a proton pump inhibitor (standard dose, twice daily). Since the patient was still complaining of dyspepsia and severe gastric pain, the gastroenterologist sent gastric tissue samples from the antrum and corpus to our diagnostic laboratory for microbiological investigation in January 2006. The gastric specimens were homogenized and cultured on Columbia-Agarbased culture medium containing 10% (v/v) washed human erythrocytes and 10% (v/v) heat inactivated horse serum (HHPplates) under microaerophilic conditions at 37 C for 72 h. Grown bacteria were identified as H. pylori by typical morphology of
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