Vancomycin minimum inhibitory concentrations (MICs) for meticillin-resistant Staphylococcus aureus (MRSA) in Hong Kong

Vancomycin minimum inhibitory concentrations (MICs) for meticillin-resistant Staphylococcus aureus (MRSA) in Hong Kong

386 Letter to the Editor / International Journal of Antimicrobial Agents 36 (2010) 383–389 Table 1 Microsporum canis minimum inhibitory concentratio...

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386

Letter to the Editor / International Journal of Antimicrobial Agents 36 (2010) 383–389

Table 1 Microsporum canis minimum inhibitory concentrations (MICs) of the tested strain population. Drug

Griseofulvin Fluconazole Itraconazole Posaconazole Terbinafine

ANOVA-defined groupsa

MIC (␮g/mL) Range

GM (95% CI)

MIC50

0.064 to 8 0.25 to 64 0.064 to 1 0.032 to 0.5 0.032 to 4

0.33 (0.199–0.528) 6.20 (3.10–12.41) 0.13 (0.100–0.181) 0.12 (0.148–0.491) 0.29 (0.096–0.158)

0.25 8 0.125 0.125 0.25

MIC90 2 64 0.5 0.25 4

B A C C BCb

GM, geometric mean; 95% CI, 95% confidence interval; MIC50/90 , MICs for 50% and 90% of the organisms, respectively; ANOVA, analysis of variance. a Antifungal agent MICs marked with different letters are significantly different. b MICs not significantly different from those of posaconazole and itraconazole.

skin levels of >1 ␮g/mL at 400 mg twice daily for 8 days [7]. Further studies could clarify in vivo–in vitro associations between MIC values and posaconazole levels attained in hair. By contrast, maximum concentrations in hair of 2.34 ␮g/mL are only reported for terbinafine at a dose of 250 mg qd for 28 days [12]. Terbinafine MICs for 5 of 28 isolates were higher than the maximum concentrations reported in hair. This could account for treatment failures reported for M. canis-related tinea capitis in children [2]. None the less, in vivo localisation of M. canis arthroconidia outside the hair shaft may further complicate drug–fungus interactions, which might also lead to treatment failure. How M. canis in vitro testing translates to clinical predictability currently remains unknown. Thus, future mining data from constructed MIC databases from susceptibility testing can support treatment optimisation schemes for M. canis-related dermatophytoses.

[12] Faergemann J, Zehender H, Denouël J, Millerioux L. Levels of terbinafine in plasma, stratum corneum, dermis–epidermis (without stratum corneum), sebum, hair and nails during and after 250 mg terbinafine orally once per day for four weeks. Acta Derm Venereol 1993;73:305–9.

Michael Arabatzis ∗ Miltiades Kyprianou Aristea Velegraki Mycology Laboratory, Department of Microbiology, Medical School, National and Kapodistrian University of Athens, Mikras Asias 75, Goudi 11527, Athens, Greece Antonia Makri Aliki Voyatzi Microbiology Laboratory, Penteli’s Pediatric Hospital, Penteli, Greece ∗ Corresponding

author. Tel.: +30 210 746 2146; fax: +30 210 746 2147. E-mail address: [email protected] (M. Arabatzis)

Acknowledgment Afroditi Milioni for proficient technical assistance. Funding: Research grants SARG K.A. 70/3/5905 and 70/3/6915 from the National and Kapodistrian University of Athens (Athens, Greece). Competing interests: AVe has received unrestricted research grants from Pfizer and Schering-Plough. Ethical approval: Not required.

doi:10.1016/j.ijantimicag.2010.06.032

References

Sir,

[1] Hay RJ, Robles W, Midgley G, Moore MK; European Confederation of Medical Mycology Working Party on Tinea Capitis. Tinea capitis in Europe: new perspective on an old problem. J Eur Acad Dermatol Venereol 2001;15: 229–33. [2] Hofbauer B, Leitner I, Ryder NS. In vitro susceptibility of Microsporum canis and other dermatophyte isolates from veterinary infections during therapy with terbinafine or griseofulvin. Med Mycol 2002;40:179–83. [3] Koussidou-Eremondi T, Devliotou-Panagiotidou D, Mourellou-Tsatsou O, Minas A. Epidemiology of dermatomycoses in children living in Northern Greece 1996–2000. Mycoses 2005;48:11–6. [4] Clinical and Laboratory Standards Institute. Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; approved standard. 2nd ed. Document M38-A2. Wayne, PA: CLSI; 2008. [5] Ghannoum MA, Chaturvedi V, Espinel-Ingroff A, Pfaller MA, Rinaldi MG, LeeYang W, et al. Intra- and interlaboratory study of a method for testing the antifungal susceptibilities of dermatophytes. J Clin Microbiol 2004;42:2977–9. [6] Barchiesi F, Arzeni D, Camiletti V, Simonetti O, Cellini A, Offidani AM, et al. In vitro activity of posaconazole against clinical isolates of dermatophytes. J Clin Microbiol 2001;39:4208–9. [7] Krishna G, Beresford E, Ma L, Vickery D, Martinho M, Yu X, et al. Skin concentrations and pharmacokinetics of posaconazole after oral administration. Antimicrob Agents Chemother 2010;54:1807–10. [8] Artis WM, Odle BM, Jones HE. Griseofulvin-resistant dermatophytosis correlates with in vitro resistance. Arch Dermatol 1981;117:16–9. [9] Verweij PE, Howard SJ, Melchers WJG, Denning DW. Azole-resistance in Aspergillus: proposed nomenclature and breakpoints. Drug Resist Updat 2009;12:141–7. [10] Gupta AK, Kohli Y, Batra R. In vitro activities of posaconazole, ravuconazole, terbinafine, itraconazole and fluconazole against dermatophyte, yeast and nondermatophyte species. Med Mycol 2005;43:179–85. [11] Ghannoum MA, Wraith LA, Cai B, Nyirady, Isham N. Susceptibility of dermatophyte isolates obtained from a large worldwide terbinafine tinea capitis clinical trial. Br J Dermatol 2008;159:711–3.

Meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia is associated with high morbidity and mortality [1]. Increasing evidence in the literature indicates that treatment success with vancomycin decreases as the vancomycin minimum inhibitory concentration (MIC) of the MRSA strain increases [2]. Significantly higher mortality in MRSA infections was documented when vancomycin was used for the treatment of MRSA strains despite vancomycin MICs in the susceptible category (MIC ≤ 2 ␮g/mL) [3,4]. This led to suggestions that alternative anti-MRSA therapies might be considered as well as to lowering of the vancomycin breakpoint further for S. aureus infections. A consensus review from the American Society of Health-System Pharmacists, the Infectious Diseases Society of America and the Society of Infectious Diseases Pharmacists [5] on the use of vancomycin indicated that a target area under the serum drug concentration–time curve (AUC)/MIC ratio of ≥400 was predictive of S. aureus eradication and that this would be unlikely to be achievable when the MRSA vancomycin MIC reaches 2 mg/L. A higher dose of vancomycin (>1 g every 12 h) would also be necessary when the MIC is ≥1 mg/L. The recommendation from the Clinical and Laboratory Standards Institute (CLSI) in 2008 [3] to perform MIC testing in order to determine the susceptibility of all isolates of staphylococci to vancomycin may provide further support to the clinical correlation of vancomycin MIC breakpoints. Controversies regarding vancomycin susceptible breakpoints are further complicated by recent reports indicating that the MIC

13 May 2010

Vancomycin minimum inhibitory concentrations (MICs) for meticillin-resistant Staphylococcus aureus (MRSA) in Hong Kong

Letter to the Editor / International Journal of Antimicrobial Agents 36 (2010) 383–389

Fig. 1. Minimum inhibitory concentrations (MICs) of vancomycin for 100 nonduplicate meticillin-resistant Staphylococcus aureus (MRSA) clinical isolates, Hong Kong, March–August 2008.

values generated vary significantly depending on the method used for MIC determination [6]. Significant differences in MICs have been detected with the Etest versus broth microdilution (BMD) or agar dilution [6]. We examined the vancomycin MICs of 100 non-duplicate MRSA clinical isolates using two methods, namely the BMD method according to the CLSI and the Etest (AB BIODISK, Solna, Sweden) plated onto Mueller–Hinton agar (Oxoid Ltd., Cambridge, UK) according to the manufacturer’s recommendations. MRSA isolates were from hospitalised patients with confirmed MRSA infection admitted to the Prince of Wales Hospital, Hong Kong, during the 6-month period from March–August 2008. Isolates included those obtained from pus, body fluids, sputum and urine and were stored in 10% brain–heart infusion glycerol at −70 ◦ C until tested. The identity of S. aureus was confirmed by colonial morphology, Gram stain and coagulase test. Meticillin resistance was screened by the oxacillin (1 ␮g) disk susceptibility test according to the CLSI [3]. Staphylococcus aureus ATCC 25923 was included as a control and the MICs were interpreted according to the CLSI [3]. The MICs of vancomycin for MRSA are shown in Fig. 1. All MRSA isolates were susceptible to vancomycin (MIC ≤ 2.0 ␮g/mL) by the two methods. However, the percentage of isolates with a vancomycin MIC at 2.0 ␮g/mL based on BMD versus Etest was 4% compared with 9%. An additional 54% of MRSA isolates would have higher MICs > 1.0 ␮g/mL as determined by Etest. This is similar to previous studies whereby the Etest produced MIC values one dilution higher than the values determined by the CLSI reference method [6]. Subsequent reports also demonstrated such findings using both BMD and agar dilution, even when arithmetic incremental dilutions of vancomycin were included in the BMD method. Other studies have used different media, including brain–heart infusion agar and Mueller–Hinton agar with or without cation adjustment (BD Diagnostics, Franklin Lakes, NJ, and Oxoid Ltd.) for performing Etests, and this produced further variabilities to the geometric mean vancomycin MICs in MRSA at the higher end of the CLSI susceptible breakpoint. This adds further challenges to comparisons of vancomycin MIC values with clinical outcome when differing methodologies are used. Vancomycin is still the mainstay of choice in the treatment of MRSA infection in Hong Kong and much of the Asia-Pacific region. In the current study, the MRSA isolates were reportedly all susceptible to vancomycin. A recent study of Hong Kong MRSA also

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demonstrated vancomycin susceptibility, but a rising geometric mean vancomycin MIC was observed amongst isolates from 1997 to 2008 [7]. As newer anti-MRSA agents are made available, there is a shift towards using alternative agents such as linezolid or daptomycin for MRSA infection for isolates that give a vancomycin MIC > 1 ␮g/mL. However, it would be difficult to extrapolate these MIC data for clinical correlation of treatment outcome, as well as making recommendations to switch to alternative agents, when MIC values vary significantly by the choice of method used. This highlights that further evaluation with comparison of the methodologies is warranted as well as careful scrutiny of the methods chosen for MIC determination before interpretation as to rising vancomycin MICs and decisions regarding choice of anti-MRSA treatment. Funding: This study was supported by a grant from AstraZeneca (Hong Kong) Ltd. Competing interests: MI was the principal investigator for the AstraZeneca (Hong Kong) Ltd. grant. Ethical approval: Not required.

References [1] You JHS, Ip DNC, Wong CTN, Ling T, Lee N, Ip M. Meticillin-resistant Staphylococcus aureus bacteraemia in Hong Kong. J Hosp Infect 2008;70:379–81. [2] Sakoulas G, Moise-Broder PA, Schentag J, Forrest A, Moellering Jr RC, Eliopoulos GM. Relationship of MIC and bactericidal activity to efficacy of vancomycin for treatment of methicillin-resistant Staphylococcus aureus bacteremia. J Clin Microbiol 2004;42:2398–402. [3] Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing. Eighteenth informational supplement. Document M100-S18. Wayne, PA: CLSI; 2008. [4] Soriano A, Marco F, Martínez JA, Pisos E, Almela M, Dimova VP, et al. Influence of vancomycin minimum inhibitory concentration on the treatment of methicillinresistant Staphylococcus aureus bacteremia. Clin Infect Dis 2008;46:193–200. [5] Rybak M, Lomaestro B, Rotschafer JC, Moellering Jr R, Craig W, Billeter M, et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm 2009;66:82–98 [Erratum in: Am J Health Syst Pharm 2009;66:887]. [6] Prakash V, Lewis JS, Jorgensen JH. Vancomycin MICs for methicillin-resistant Staphylococcus aureus isolates differ based upon the susceptibility test method used. Antimicrob Agents Chemother 2008;52:4528. [7] Ho PL, Lo PY, Chow KH, Lau EHY, Lai EL, Cheng VCC, et al. Vancomycin MIC creep in MRSA isolates from 1997 to 2008 in a healthcare region in Hong Kong. J Infect 2010;60:140–5.

Margaret Ip ∗ Shirley S.L. Chau Sau Lai Lui Eric Leung Thomas Ling Department of Microbiology, Faculty of Medicine, The Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, Shatin, N.T., Hong Kong ∗ Corresponding

author. Tel.: +852 2632 1265; fax: +852 2647 3227. E-mail address: [email protected] (M. Ip) 18 June 2010 doi:10.1016/j.ijantimicag.2010.06.039

Post-antibiotic effect (PAE) of moxifloxacin in multidrugresistant Stenotrophomonas maltophilia Sir, Stenotrophomonas maltophilia has emerged as a cause of nosocomial infections, especially in patients with debilitating conditions such as intensive care hospitalisation, immunosuppression, neu-