Meticillin-sensitive and -resistant Staphylococcus aureus: competition and co-carriage

Letters to the Editor with 49% on CHROMagar S. aureus and 66% on mannitol salt agar. MRSA ID is adapted from S. aureus ID by the inclusion of cefoxitin, and this medium allowed the successful isolation of the strain reported here.6 The fact that EMRSA-15 could not be detected in a tracheostomy swab using conventional culture media is a cause for concern from both a diagnostic and an infection control viewpoint. Resubmission of the thymidine-dependent variant in simulated samples as an internal quality assessment exercise confirmed that this strain could not be detected using conventional media. We hypothesize that auxotrophic variants of MRSA may potentially be an unrecognized reservoir of MRSA in the hospital setting, and suggest that further studies are warranted to examine the prevalence of such strains. Media such as blood agar, with or without selective enrichment, remain widely used for the detection of MRSA7 but may not support the growth of such variants.5 Microbiologists need to be aware of the possibility of such strains persisting in patients who have had long-term antimicrobial therapy, particularly with trimethoprim-sulphamethoxazole. In such patients, laboratory methods may need to be varied to optimize recovery of these strains.5,8

References 1. Acar JF, Goldstein FW, Lagrange P. Human infections caused by thiamine- or menadione-requiring Staphylococcus aureus. J Clin Microbiol 1978;8:142e147. 2. Seifert H, von Eiff C, Fatkenheuer G. Fatal case due to methicillin-resistant Staphylococcus aureus small colony variants in an AIDS patient. Emerg Infect Dis 1999;5:450e453. 3. Gilligan PH, Gage PA, Welch DF, Muszynski MJ, Wait KR. Prevalence of thymidine-dependent Staphylococcus aureus in patients with cystic fibrosis. J Clin Microbiol 1987;25: 1258e1261. 4. Kahl B, Herrmann M, Everding AS, et al. Persistent infection with small colony variant strains of Staphylococcus aureus in patients with cystic fibrosis. J Infect Dis 1998;177:1023e 1029. 5. Kipp F, Kahl BC, Becker K, et al. Evaluation of two chromogenic agar media for recovery and identification of Staphylococcus aureus small-colony variants. J Clin Microbiol 2005; 43:1956e1959. 6. Perry JD, Davies A, Butterworth LA, Hopley AL, Nicholson A, Gould FK. Development and evaluation of a chromogenic agar medium for methicillin-resistant Staphylococcus aureus. J Clin Microbiol 2004;42:4519e4523. 7. Wertheim HF, Vos MC, Boelens HA, et al. Low prevalence of methicillin-resistant Staphylococcus aureus (MRSA) at hospital admission in the Netherlands: the value of search and destroy and restrictive antibiotic use. J Hosp Infect 2004;56:321e325. 8. Kipp F, Becker K, Peters G, von Eiff C. Evaluation of different methods to detect methicillin resistance in small-colony

229 variants of Staphylococcus aureus. J Clin Microbiol 2004; 42:1277e1279.

V.J. Cleeve* J.D. Perry G. Cresswell K.E. Orr Department of Microbiology, Freeman Hospital, Newcastle upon Tyne, UK E-mail addresses: [email protected], [email protected] Available online 4 April 2006 * Corresponding author. Address: Department of Microbiology, Freeman Hospital, Freeman Road, High Heaton, Newcastle upon Tyne NE7 7DN, UK. Tel.: þ44 191 2336161. ª 2005 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jhin.2005.11.009

Meticillin-sensitive and -resistant Staphylococcus aureus: competition and co-carriage Madam, Kampf questioned the methodology used in our study on the possible protective effect of meticillinsensitive Staphylococcus aureus (MSSA) against colonization with meticillin-resistant S. aureus (MRSA), and raised a number of interesting issues about the implication of our conclusion.1,2 Kampf was concerned about the oxacillin concentration used to isolate MRSA from screening swabs. We classified an isolate as resistant if it grew on the primary plate of mannitol salt agar (MSA) containing 4 mg/L of oxacillin, which is still widely used for MRSA screening. The British Society of Antimicrobial Chemotherapy guidelines for the laboratory diagnosis and testing of MRSA acknowledge that no single medium will recover all MRSA strains.4 High sensitivity and specificity in detecting MRSA using MSA with an oxacillin concentration of 2 mg/L has been reported,5 although studies with pure culture from a collection of staphylococcal strains cannot be a substitute for comparative studies that assess clinical specimens.4 Interestingly, data from Antibiotic Resistance: Prevention and Control (ARPAC) (available on the ARPAC website) indicate that, of the European centres that reported the use of oxacillin screening plates, 8.9% use an

230 oxacillin concentration of 4 mg/L, while 69.6% use an even higher concentration. To maximize the recovery of all S. aureus strains, we plated all swabs on to a blood agar plate and on a MSA plate in addition to MSA supplemented with oxacillin. Evaluation of the sensitivity and specificity of a screening media was not the aim of our study. Central to our study was the detection of MRSA/ MSSA co-colonization. When MRSA grew, we tested 30 S. aureus colonies growing from non-selective media (even if they all looked the same morphotype) for meticillin sensitivity with a meticillin single concentration strip (MAST Diagnostics, Merseyride, UK). Kampf suggested that adding NaCl to the Isosensitest agar would achieve the maximum detection rate for MRSA. MAST recommends either the addition of NaCl or incubation at 30
C. Results obtained with meticillin as well as oxacillin are representative of resistance to all beta-lactam agents.4 Kampf was also concerned that we did not show clonal non-identity of co-colonizing MRSA and MSSA, and that some of the co-carriers may, in fact, have been the same strain expressing a different degree of resistance to oxacillin. It is our opinion that genotype studies would not affect the conclusions of our study, as recent reports suggest that the S. aureus population is clonal.3 Nonetheless, if Kampf is correct in suggesting that some of the co-carriers were, in fact, colonized with either MRSA or MSSA, this would strengthen (not weaken) our conclusion that S. aureus bacterial colonization is not randomly distributed and that there must be some competitive exclusion in operation. With reference to our results, we detected four co-carriers: one grew predominantly MSSA colonies (MSSA:MRSA ¼ 29:1); two grew predominantly MRSA colonies (1:31 and 3:30); and one had comparable numbers of colonies (16:8).2 In the absence of molecular data, we used the more conservative approach of accepting the results at face value [resulting in a protective efficacy (PE) of MSSA against MRSA of 78%, P ¼ 0.012; Table III of Dall’Antonia et al.]. If we accept Kampf’s suggestion that two of the co-carriers (1:31 and 3:30) were, in fact, pure MRSA carriers, we obtain more significant results (PE ¼ 93%, P ¼ 0.009). It seems unlikely that the other co-carriers were true MRSA carriers, but if we assume them all to be MRSA carriers, we would obtain even greater PEs. Kampf concluded his letter by opening an interesting debate: what is the right approach to nasal colonization with S. aureus? The majority of S. aureus infections arise in patients with nasal colonization, and nasal carriers have a higher risk of developing a bacteraemia with S. aureus.6 Nasal

Letters to the Editor decontamination has been shown to reduce the risk of S. aureus surgical wound infection in cardiothoracic patients and peritonitis in patients undergoing peritoneal dialysis. On the other hand, inpatient mortality rates attributable to S. aureus bacteraemia may be higher in non-carriers of S. aureus than in carriers.7 Although the mechanism for a competitive effect is yet to be demonstrated, should MRSA and MSSA strains compete for colonization space in the anterior nares, this might explain the success of Shinefield et al.’s artificial inoculation strategy.8 In the 1950s, they inoculated neonates with a ‘nonpathogenic’ S. aureus strain (502A) to control outbreaks of virulent S. aureus strains in neonatology wards in the USA. The spread of virulent clones (multi-resistant or not) could be helped by the destruction of the resident microbiota, either through deliberate attempts at decontamination or as a collateral effect of the widespread use of broad-spectrum antibiotics.

References 1. Kampf G. What should be done with nasal Staphylococcus aureus carriers? J Hosp Infect 2005;61:353e354. 2. Dall’Antonia M, Coen PG, Wilks M, et al. Competition between methicillin-sensitive and -resistant Staphylococcus aureus in the anterior nares. J Hosp Infect 2005;61:62e67. 3. Melles DC, Gorkink RFJ, Boelens HAM, et al. Natural population dynamics and expansion of pathogenic clones of Staphylococcus aureus. J Clin Invest 2004;114:1732e1740. 4. Brown DFJ, Edwards DI, Hawkey PM, et al. Joint Working Party of the British Society for Antimicrobial Chemotherapy, Hospital Infection Society and Infection Control Nurses Association. Guidelines for the laboratory diagnosis and susceptibility testing of methicillin-resistant Staphylococcus aureus (MRSA). J Antimicrob Chemother 2005;56:1000e1018. 5. Kampf G, Lecke C, Cimbal AK, Weist K, Ruden H. Evaluation of mannitol salt agar for detection of oxacillin resistance in Staphylococcus aureus by disk diffusion and agar screening. J Clin Microbiol 1998;36:2254e2257. 6. van Eiff C, Becker K, Machka K, et al. Nasal carriage as a source of Staphylococcus aureus bacteremia. N Engl J Med 2001;344:11e16. 7. Wertheim HFL, Vos M, Ott A, et al. Risk and outcome of nosocomial Staphylococcus aureus bacteremia in nasal carriers versus non-carriers. Lancet 2004;364:703e705. 8. Shinefield HR, Ribble JC, Boris M, Eichenwald HF, Aly R, Maibach H. Bacterial interference between strains of S. aureus. Am J Dis Child 1974;236:444e455.

M. Dall’Antoniaa,* P. Gregory Coenb M. Wilksc M.R. Millard a Queen Elizabeth Hospital NHS Trust, London, UK

Letters to the Editor

231 b

Infection Control Office, Department of Microbiology, The Windeyer Institute of Medical Science, University College London Hospitals NHS Trust, London, UK c Department of Microbiology and Virology, St Bartholomew’s Hospital, Barts and the London NHS Trust, London, UK d Department of Medical Microbiology, Barts and the London NHS Trust, Royal London Hospital, London, UK E-mail address: [email protected] Available online 18 April 2006 * Corresponding author. Address: Queen Elizabeth Hospital NHS Trust, Stadium Road, Woolwich, London SE18 4QH, UK. Tel.: þ44 208 836 5698. ª 2006 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.

through’ penetration. The test described by Strohal et al. uses a much smaller area and will not in any way test for ‘strike-around’. We later demonstrated3 that evaporation of water vapour from the surface of the dressing enhances its impermeability to bacteria. The ability of the dressing to permit the evaporation of water vapour is viewed as a positive property. As a final point, the value of using hydrocolloids as an MRSA barrier over lesions was incorporated into our scoring system.4 The score it was given recognized the effectiveness of occlusive hydrocolloid dressings in that it was given the same value as a patient receiving specific anti-MRSA antibiotics. Throughout these studies, we were using occlusive dressings and none of the dressings tested contained silver. From this point of view alone, we would agree with Strohal et al. that they have a relatively ‘new solution’.

doi:10.1016/j.jhin.2006.02.001

References Nanocrystalline silver dressings as an efficient anti-MRSA barrier: not a new solution to an increasing problem? Madam, We read with interest the recent paper by Strohal et al.1 and we fear that the paper is not as novel as it might appear. In 1988, we reported the use of hydrocolloid dressings to reduce the amount of isolation required by patients.2 We demonstrated in seven patients that it was possible to save 91 bed-days, which would have been in isolation, to the benefit of both the patients (enabling mobilization to take place) and the hospital (financial). This saving was achieved by using the dressings as an efficient anti-meticillin-resistant Staphylococcus aureus (MRSA) barrier. We also identified a method of challenging the permeability of dressings to MRSA, which revealed substandard batches of hydrocolloid dressings as well as offering a test that would compare different hydrocolloid dressings. The laboratory tests confirmed that the dressings could be used to contain the outward spread of MRSA from colonized wounds. Our test did not measure the ability of staphylococci to spread between the adhesive and the skin (strike-around), and it was designed to simulate a wound that is exuding very heavily. It has the advantage of offering a large surface area so that it offers a good challenge for ‘strike-

1. Strohal R, Schelling M, Takacs M, Jurecka W, Gruber U, Offner F. Nanocrystalline silver dressings as an efficient anti-MRSA barrier: a new solution to an increasing problem. J Hosp Infect 2005;60:226e230. 2. Wilson P, Burroughs D, Dunn L. Methicillin-resistant Staphylococcus aureus and hydrocolloid dressings. Pharm J 1988;241: 787e788. 3. Wilson P, Dunn LJ. The development of biofilm hydrocolloid dressings e permeability to bacteria. Pharm J 1995;254: 232e235. 4. Wilson P, Dunn LJ. Using an MRSA isolation scoring system to decide whether patients should be nursed in isolation. Hyg Med 1996;21:465e477.

P. Wilson* L. Dunn Department of Medical Microbiology, Royal London Hospital, London, UK E-mail address: peter.wilson@bartsandthelondon. nhs.uk Available online 4 April 2006

* Corresponding author. Address: Department of Medical Microbiology, Royal London Hospital, 37 Ashfield Street, London E1 1BB, UK. Tel.: þ44 20 7377 7000x2009; fax: þ44 20 7377 7330. ª 2006 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jhin.2006.01.016