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96 Letters to the Editor / International Jour

3] van Eiff C, Friedrich AW, Becker K, Peters G. Comparative invitro activity of ceftobiprole against staphylococci displaying normaland small-colony variant phenotypes. Antimicrob Agents Chemother2005;49:4372–4.

4] Hebeisen P, Heinze-Krauss I, Angehrn P, Hohl P, Page MG, Then RL.In vitro and in vivo properties of Ro 63-9141, a novel broad-spectrumcephalosporin with activity against methicillin-resistant staphylococci.Antimicrob Agents Chemother 2001;45:825–36.

5] Goldstein EJC, Citron DM, Merriam CV, Warrern YA, Tyrrell KL,Fernandez HT. In vitro activity of ceftobiprole against aerobic and anaer-obic strains isolated from diabetic foot infections. Antimicrob AgentsChemother 2006;50:3959–62.

6] Bannerman TL. Staphylococcus, micrococcus, and other catalase-positive cocci that grow aerobically. In: Murray P, Baron EJ, JorgensenJH, Pfaller MA, Yolken RH, editors. Manual of clinical microbiology.8th ed. Washington, DC: ASM Press; 2003. p. 384–404.

7] Clinical and Laboratory Standards Institute. Methods for dilution antimi-crobial susceptibility tests for bacteria that grow aerobically. 7th ed.Approved standard. Document M7-A7. Wayne, PA: CLSI; 2006.

Velusamy Srinivasan 1

John E. McGowan Jr ∗Department of Epidemiology, Rollins School of Public

Health, Emory University, 1518 Clifton Road NE,Atlanta, GA 30322, USA

Sigrid McAllisterFred C. Tenover

Division of Healthcare Quality Promotion, Centers forDisease Control and Prevention, Atlanta, GA 30333, USA

∗ Corresponding author. Tel.: +1 404 727 9365;fax: +1 404 727 8737.

E-mail address: jmcgowa@sph.emory.edu(J.E. McGowan Jr)

1 Present address: 206 Biosystems Engineering andnvironmental Sciences, The University of Tennessee, 2506

E.J. Chapman Drive, Knoxville, TN 37996, USA.

oi: 10.1016/j.ijantimicag.2007.10.027

e: A global survey of antibiotic leftovers in the outpatientetting

Sir,The concern about utility or otherwise of antibiotic left-

vers in 11 countries has been very truthful [1]. Surely futurentibiotic dispensing in exact numbers of doses as well aselevant information campaigns to educate the public woulde commendable. Nevertheless, for a comprehensive strike its important to recognise the value of storage provisions forntibiotics. Antibiotics require constant storage at controlledemperatures ranging from sub zero, to 2–8 ◦C or 10–25 ◦C2]. They may be inadvertently subjected to a harsh environ-ent prior to administration to patients, resulting in reduced

otency. During the 1995 heat wave in Chicago, the tempera-

ure was 40 ◦C but the heat index, an estimate of evaporativend radiative transfer of heat, was 48.3 ◦C [3]. Different agen-ies collaborated to minimise the harmful effects of heatn humans; however, therapeutics, including antimicrobials,

ic

ntimicrobial Agents 31 (2008) 290–298

ere ignored. Furthermore, electrical appliances are essen-ial in the maintenance of constant temperature. Whilst erraticower supply is a rule rather than the exception in many coun-ries, the picture during hurricane Katrina in New Orleansuring 2005 was shocking. The prolonged power cut wasccompanied by auxiliary generators running out of fuel [4].

Prospective global research to eliminate misuse of antibi-tics [1] should also probe storage practices in warehouses,hysicians’ offices, and pharmacy and non-pharmacy sites. Inhe interim phase, a campaign is essential to educate regard-ng storage needs through symbols. This could be feasible byroposing distinct symbols indicating the recommended stor-ge temperature on antibiotic vials, capsules or tablets. Thishould not be an insurmountable task since distinct marks areandatory for containers of poisons, radioactive materials

nd inflammables, and are in universal usage.The quality of antibiotics offered in different countries

ther than the 11 countries [1] points to inadvertent salef poor-quality medicines. Representative retrieved lots ofntibiotics leftover or otherwise in the above countries woulde ideal to rule out inadvertent usage of poor-quality antibi-tics.

Funding: No funding sources.Competing interests: None declared.Ethical approval: Not required.

eferences

1] Kardas P, Pechere J-C, Hughes DA, Cornaglia G. A global survey ofantibiotic leftovers in the outpatient setting. Int J Antimicrob Agents2007;30:530–6.

2] 2007 Physicians’ Desk Reference. 61st ed. Montvale, NJ: Medical Eco-nomics Company; 2007.

3] Centers for Disease Control and Prevention (CDC). Heat-relatedmortality—Chicago, July 1995. MMWR Morb Mortal Wkly Rep1995;44:577–9.

4] Dalton R. Health centres and labs left reeling by Katrina. Nature2005;437:177.

Subhash C. Arya ∗Nirmala Agarwal

Sant Parmanand Hospital, 18 Alipore Road, Delhi 110054,India

∗ Corresponding author. Tel.: +91 119810642269.E-mail address: subhashji@hotmail.com (S.C. Arya)

oi: 10.1016/j.ijantimicag.2007.11.005

n vitro activity of fosfomycin tromethamine and line-olid against vancomycin-resistant Enterococcus faeciumsolates

Sir,Enterococcal nosocomial infections are becoming

ncreasingly important. Enterococcus faecalis and Entero-occus faecium are the two species responsible for the most

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Letters to the Editor / International Jour

nterococcal infections [1]. Both species may be resistant toultiple drugs, including vancomycin.Fosfomycin tromethamine (FT), which is derived from

hosphonic acid and affects cell wall synthesis by inhibitionf enolpyruvate transferase, has entered the Turkish marketery recently. It is active against many urinary pathogensncluding strains of Escherichia coli, Staphylococcus sapro-hyticus and Enterococcus spp. Although FT has been onhe market for the last 2 years in Turkey, there are no dataegarding its activity against vancomycin-resistant E. faeciumVREF).

Linezolid is an oxazolidinone group antibiotic that inhibitshe formation of the initiation complex constructed with 50Sibosomes, mRNA, initiation factors 2 and 3, and fMetRNA2]. It has significant activity against Gram-positive bacteria,ncluding VREF.

Treatment of infections caused by VREF is challengingwing to the limited number of effective antimicrobials. Inhe present study, the in vitro activities of FT and linezolidgainst VREF were evaluated.

Study strains were isolated from different specimens (89ectal swabs, 24 blood cultures, 3 tissue biopsy cultures and

urine culture) of hospitalised patients between 2000 and006. Minimum inhibitory concentrations (MICs) of FT andinezolid were determined by Etest (AB BIODISK, Solna,weden). A 0.5 McFarland suspension of the microorgan-

sms in 0.9% saline was inoculated into Mueller–Hinton agarOxoid, Basingstoke, UK). Etest strips were placed on theulture plates and the MIC was read after 24 h. Since Etesttrips for FT contained glucose-6-phosphate, extra supple-entation of the compound in the culture medium was not

one. The readings were tabulated and the MICs of 50% and0% of the organisms (MIC50 and MIC90 values, respec-ively) were determined. The breakpoint criteria to determineusceptibility were based on those of the Clinical and Labora-ory Standards Institute [3]. All isolates were E. faecium. The

IC90 and MIC50 values were, respectively, 512 mg/L and92 mg/L for FT and 2 mg/L and 1 mg/L for linezolid. Over-ll MIC values for linezolid ranged between 0.5 mg/L andmg/L. All isolates were found to be susceptible to linezolid,hereas 113/117 isolates were resistant to FT. Since most

ntimicrobial agents exhibit poor in vitro activity againstnterococci, the options for treatment of severe infections areenerally restricted either to a glycopeptide or a �-lactam plusn aminoglycoside. All study isolates had high-level resis-ance to gentamicin (data not shown). Linezolid was foundo be more active than FT in our collection, in agreement withrevious reports [1,4,5].

FT was found to have relatively poor in vitro activitygainst VREF strains in our study. Allerberger and Klare [6]eported FT MICs for VREF isolates in the intermediate sen-itivity range, yielding an MIC50 of 32 mg/L and an MIC90 of

4 mg/L. In contrast, it was reported that FT had high activ-ty against enterococcal strains in some other studies [4,7].he MIC50 and MIC90 values of FT in our study strains wereuch higher than previous reports. Bacterial resistance to FT

ntimicrobial Agents 31 (2008) 290–298 297

an be either chromosomal or plasmid-mediated. FT is takennto cells by active transport through the partially constitutivelycerophosphate uptake system and by a secondary trans-ort system that mediates hexose monophosphate uptake.ost chromosomally resistant mutants have an impairment

n one or both of these uptake systems. Unfortunately, weo not know the resistance mechanisms of the strains in thistudy.

In conclusion, in contrast to FT, linezolid had good in vitroctivity against 117 isolates of VREF. FT does not appear toe a good choice in VREF urinary tract infections but maye an alternative in infections with low MIC values.

Funding: Departmental sources.Competing interests: S.U. received speaker’s honoraria

rom Pfizer.Ethical approval: Not required.

eferences

1] Reis AO, Corderio JCR, Machado AMO, Sader HS. In vitro activityof linezolid tested against vancomycin-resistant enterococci isolated inBrazilian hospitals. Braz J Infect Dis 2001;5:243–51.

2] Noskin GA, Siddiqui F, Stosor V, Hacek D, Peterson LR. Invitro activities of linezolid against important Gram-positive bacte-rial pathogens including vancomycin-resistant enterococci. AntimicrobAgents Chemother 1999;43:2059–62.

3] Clinical and Laboratory Standards Institute. Performance standards forantimicrobial susceptibility testing. Sixteenth informational supplement.M100-S16. Wayne, PA: CLSI; 2006.

4] Shrestha NK, Chua JD, Tuohy MJ, Wilson DA, Procop GW, LongworthDL, et al. Antimicrobial susceptibility of vancomycin-resistant Ente-rococcus faecium: potential utility of fosfomycin. Scand J Infect Dis2003;35:12–4.

5] Murray BE. Vancomycin-resistant enterococcal infections. N Engl J Med2000;342:710–21.

6] Allerberger F, Klare I. In-vitro activity of fosfomycin againstvancomycin-resistant enterococci. J Antimicrob Chemother1999;43:211–7.

7] Perri MB, Hersberger E, Ionescu M, Lauter C, Zervos MJ. In vitro sus-ceptibility of vancomycin-resistant enterococci (VRE) to fosfomycin.Diagn Microbiol Infect Dis 2002;42:269–71.

Feriha CilliDepartment of Microbiology and Clinical Microbiology,

Ege University Faculty of Medicine, Bornova, Izmir, Turkey

Husnu PullukcuDepartment of Infectious Diseases and Clinical

Microbiology, Ege University Faculty of Medicine,Bornova, Izmir, Turkey

Sohret AydemirDepartment of Microbiology and Clinical Microbiology,

Ege University Faculty of Medicine, Bornova, Izmir, Turkey

Oguz Resat Sipahi ∗

Meltem Tasbakan

Department of Infectious Diseases and ClinicalMicrobiology, Ege University Faculty of Medicine,

Bornova, Izmir, Turkey

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fax: +90 232 342 08 71.E-mail address: oguz.resat.sipahi@ege.edu.tr (O.R. Sipahi)

98 Letters to the Editor / International Jour

Ajda TurhanDepartment of Microbiology and Clinical Microbiology,

Ege University Faculty of Medicine, Bornova, Izmir, Turkey

Sercan UlusoyDepartment of Infectious Diseases and Clinical

Microbiology, Ege University Faculty of Medicine,Bornova, Izmir, Turkey

d

ntimicrobial Agents 31 (2008) 290–298

∗ Corresponding author. Tel.: +90 232 390 45 10;

oi: 10.1016/j.ijantimicag.2007.11.003