Antiseptic Treatment of Methicillin-resistant Staphylococcus aureus Conjunctivitis

Antiseptic Treatment of Methicillin-resistant Staphylococcus aureus Conjunctivitis

Journal of Infection (2001) 42, 166–169 doi:10.1053/jinf.2001.0805, available online at http://www.idealibrary.com on Letters to the Editor Early Pr...

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Journal of Infection (2001) 42, 166–169 doi:10.1053/jinf.2001.0805, available online at http://www.idealibrary.com on

Letters to the Editor

Early Prosthetic Valve Endocarditis due to Staphylococcus warneri with Negative Blood Culture

antibiotherapy. In the absence of positive blood cultures, surgical intervention permitted the diagnosis of endocarditis, a precise identification and evaluation of the susceptibility of the organism, and better adaptation of the antibiotherapy.

Sir, Prosthetic valve endocarditis (PVE) represents 12–33% of the reported cases of endocarditis.1 Staphylococcus warneri has never been reported as the causative agent in PVE. We describe a case of PVE due to S. warneri. The case is particularly noteworthy because of the lack of positive blood culture, emphasizing the need of both bacteriological and histological studies of heart valves when endocarditis is suspected. A 71-year-old man was operated on for severe rheumatic aortic stricture, and replacement of the aortic valve by a mechanic prosthetic valve was performed in January 1999. Cefuroxime was used as prophylactic surgical antibiotherapy. Five days later a transoesophageal echocardiogram revealed a mobile vegetation (2 cm1.5 cm) on the prosthetic valve and also suspicion of an aortic valve ring abcess. The patient was afebrile, and leukocyte count was 3109/l. The patient was empirically treated intravenously with vancomycin and gentamicin. Three blood cultures were negative. Twenty days later transoesophageal echocardiogram showed an increased transvalvular pressure gradient causing suspicion of evolutive prosthetic thrombosis. Replacement of the destroyed aortic valve by a bioprosthesis was performed. Six new blood cultures were negative. Gram staining of three vegetation tags and the aortic valve was negative. Culture of two vegetation tags and the valve yielded coagulase-negative Staphylococcus in all the media, which was identified as S. warneri by ribotyping analysis (National Reference Center, Dr El Solh). The organism was resistant to methicillin, aminoglycosides (except streptomycin) and fosfomycin, intermediate to rifampin, and susceptible to tetracycline, erythromycin, pefloxacine, trimethoprim and sulfamethoxazole, vancomycin and teicoplanin. Serologies for Coxiella, Bartonella, Brucella, Chlamydia and Candida were negative. A histopathological study of the aortic vegetation showed endocarditis lesions with an inflammatory process consisting of mononuclear cells and leukocytes. The patient received 6 weeks of intravenous vancomycin and oral pefloxacine. Successive echocardiograms showed normal prosthesis function. The patient remained well and afebrile when he was discharged from our hospital. Diagnosis of PVE is usually based on the documentation of positive blood cultures associated with new prosthetic valve dysfunction. Five to ten percent of cases of infective endocarditis (IE) are associated with negative blood culture, more frequently in prosthetic valves.2 The high mortality rate in cases of PVE suggests that early replacement of the infected prosthesis should be considered for most of the patients.3 Surgical management was indicated in our patient, because he presented with evolutive valve damage and suspicion of aortic ring abscess despite 0163-4453/01/020166;04 $35.00/0

S. Abgrall1, P. Meimoun2, A. Buu-Hoi1, J.P. Couetil2, L. Gutmann1, and J.L. Mainardi1 1 Service de Microbiologie Clinique and, 2Service de Chirurgie Cardiaque, Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75908 Paris Cedex 15, France

References 1 Whitener C, Caputo GM, Weitekamp MR, Karchmer AW. Endocarditis due to coagulase-negative staphylococci: microbiologic, epidemiologic, and clinical considerations. Inf Dis Clin North Am 1993: 7: 81–96. 2 Hoen B, Selton-Suty C, Lacassin F, Etienne J, Briançon S, Leport C, Canton P. Infective endocarditis in patients with negative blood cultures: analysis of 88 cases from a one-year nationwide survey in France. Clin Infect Dis 1995; 20: 501–506. 3 Wolf M, Witchitz S, Chastang C, Régnier B, Vachon F. Prosthetic valve endocarditis in the ICU : prognostic factors of overall survival in a series of 122 cases and consequences for treatment decision. Chest 1995; 108: 688–694. Accepted for publication 27 February 2001

doi:10.1053/jinf.2001.0804, available online at http://www.idealibrary.com on

Antiseptic Treatment of Methicillin-resistant Staphylococcus aureus Conjunctivitis Sir, Of all the infectious eye diseases, bacterial conjunctivitis is one of the most important in bed-ridden patients who have cerebrovascular accidents.1 Causative pathogens include Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Haemophilus influenzae and Pseudomonas aeruginosa.1 Antibiotic treatment of such pathogens as methicillin-resistant S. aureus (MRSA) and P. aeruginosa is very difficult because of the limited number of antibiotics available for use in ophthalmic solutions. It has recently been reported that some disinfectants or antiseptics can be effective against Staphylococcus spp.2–4 However, nosocomial outbreaks due to bacterial contamination of antiseptic solutions have also been reported.5 We describe six bed-ridden patients who have had cerebrovascular accidents and who have been treated with 0.02% benzethonium chloride for MRSA conjunctivitis; these six patients © 2001 The British Infection Society

92/female

93/male

67/female

80/female

77/female

77/female

1

2

3

4

5

6

Moderate/ bilateral eyes Large/ bilateral eyes Large/ bilateral eyes Moderate/ bilateral eyes

Small/ right eye Moderate/ bilateral eyes

Age (years)/ Amount/ sex location of pus

Patient no.

Ptosis, cerebral haemorrhage Cerebral infarction, Low blinking frequency

Cerebral infarction and haemorrhage Cerebral infarction

Cerebral infarction

Cerebral infarction

Clininical features (Risk factor)

23

22

17

10

9

3

Period of antiseptic treatment (weeks)

Table I. Features of six patients with MRSA conjunctivitis and pus secretion.

Norfloxacin and colistinerythromycin drops Colistin-erythromycin drops Chloramphenicol and colistin-erythromycin drops Wiping with sterilized water

Colistin-erythromycin drops Wiping with sterilizedwater

Treatment before antiseptic treatment

MRSA

MRSA

MRSA

MRSA

MRSA

MRSA

Isolate before antiseptic treatment

Pus secretion stopped Bacterial culture was negative Pus secretion stopped Bacterial culture was negative After treatment for 7 weeks, P. aeruginosa (alone) was detected Pus secretion stopped MRSA was detected Pus secretion stopped MRSA was detected Pus secretion decreased MRSA was detected Pus secretion decreased MRSA (alone) was detected After treatment for 4 weeks MRSA and P. aeruginosa were detected

Outcome

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Letters to the Editor

included two patients in whom P. aeruginosa ocular infection occurred during antiseptic therapy (Table I). Six bed-ridden patients at Tsushima Chuoh Hospital developed MRSA conjunctivitis after cerebrovascular accidents. Before antiseptic treatment, MRSA alone was isolated from one eye of each patient. Of the six patients, three patients had failed to respond to treatment with colistin-erythromycin, norfloxacin and/or chloramphenicol drops (patients 1, 3, 4 and 5). The eyes of two patients had been cleaned with sterilized water, but without improvement (patients 2 and 6). The eyes of all patients were wiped gently with sterilized cotton swabs freshly soaked with 0.02% benzethonium chloride four times daily. Throughout the investigation periods, the rate of pus secretion was evaluated every morning before treatment with the antiseptic. Bacterial cultures of the pus were performed once a week. MICs were determined by the agar dilution method as described by the National Committee for Clinical Laboratory Standards.6 Susceptibility testing was performed on Mueller-Hinton agar (Nippon Becton Dickinson, Tokyo, Japan). In these initial isolates, the ranges of the MICs for antibiotics were as follows: 256 ␮g/ml for cloxacillin, 256 ␮g/ml for cefminox, 128 ␮g/ml for gentamicin, 256 µg/ml for erythromycin, 8–16 ␮g/ml for chloramphenicol, 128 µg/ml for norfloxacin and 256 ␮g/ml for colistin. The disinfectant suspension test was performed as described previously.2 The MICs of disinfectants were defined as the minimum concentration (%) at which no surviving bacterium was counted following 1-min exposure to the disinfectant. The ranges of the MICs for disinfectants were as follows: 0.001–0.098% for benzethonium chloride, 0.078–0.156% for povidone iodine, 0.001–0.098% for benzalkonium chloride and 0.002–0.156% for chlorhexidine gluconate. The recommendeduse-dilution for benzethonium chloride is 0.02%. Patient 1 was a 92-year-old woman with conjunctivitis and a small amount of pus secretion (Table I). After a 3-week disinfectant treatment, there were no pathogens isolated and pus secretion stopped. Patient 2 was a 93-year-old man with conjunctivitis and a moderate amount of pus secretion (Table I). Disinfectant treatment decreased the amount of pus secretion within 3 weeks. After 7 weeks of treatment P. aeruginosa was isolated; however, MRSA was not detected and pus secretion was reduced. It was thought that the patient’s eyes could have been contaminated with P. aeruginosa due to inadequate disinfectant treatment but the MIC of benzethonium chloride was 0.005% for the P. aeruginosa isolate. Treatment was therefore continued for an additional 2 weeks, after which no further pathogens were isolated. Pus secretion stopped after 9 weeks of therapy. Patients 3, 4, and 5 were 67-, 80- and 77-year-old women, respectively, with conjunctivitis and a moderate to large amount of pus secretion (Table I). Benzethonium chloride treatment decreased the amount of pus secretion within 1–2 months in all of these patients and it became easy for these patients to open their eyes. Throughout the investigation periods MRSA strains were isolated continuously. There was no change in the MICs of disinfectants and antibiotics for the MRSA strains isolated at the end of the present study in comparison with the initial strains. Discontinuation of disinfectant therapy resulted in an increase in the rate of pus secretion in these patients. Patient 6 was a 77-year-old woman with conjunctivitis and a moderate amount of pus secretion (Table I). Disinfectant

treatment decreased the amount of pus secretion within 1 month. After 1 month, however, an increase in green-coloured pus secretion was observed and MRSA and P. aeruginosa were isolated; Treatment was continued, and P. aeruginosa was no longer detected. Pus secretion also decreased. The MIC of benzethonium chloride was 0.005% for the P. aeruginosa isolate. MRSA was isolated continuously throughout the treatment periods; however, there was no change in the MICs of disinfectants and antibiotics for MRSA isolated at the end of the present study in comparison with those of the initial isolate. In two patients, P. aeruginosa strains were isolated from pus secretions during the course of therapy with 0.02% benzethonium chloride. For these strains, MICs of benzethonium chloride were beyond the recommended use-dilution (0.02%). The treatment was therefore continued, resulting in eradication of P. aeruginosa. The emergence of P. aeruginosa in this study is surprising; patients with persistently wet or runny eyes would be expected to become colonized with benzethonium-resistant Pseudomonas spp. during long courses of treatment. In patients who secreted small to moderate amounts of pus, treatment with 0.02% benzethonium chloride effectively eradicated MRSA. In patients with moderate to large amounts of pus secretion the treatment reduced this, but failed to eradicate MRSA during the investigation periods. In two of four patients, in whom MRSA continued to be detected, there were no signs of conjunctivitis after treatment. In the other two patients slight signs of conjunctivitis remained, but these symptoms improved upon prolonged therapy. Therapy lasting for longer periods did not lead to further resistance of the MRSA isolates to disinfectants and antibiotics. We did not consider vancomycin topical treatment in the present study because vancomycin preparations are acidic and likely to induce damage in ocular tissue (personal communications with Shionogi Pharmaceutical). Secondly, vancomycin topical treatment may favour the emergence of antibiotic-resistant strains (vancomycin preparations are not available for use as ophthalmic solutions in Japan). In this small study our results suggest that therapy with 0.02% benzethonium chloride can effectively reduce pus secretion in bedridden patients with MRSA conjunctivitis. However, contamination with unpredictable pathogens such as P. aeruginosa can occur during the course of therapy.5 The use of disinfectant therapy for conjunctivitis requires both prolonged treatment and monitoring of bacterial cultures. T. Horii1,2, N. Futamura3 and Y. Suzuki2,3 Department of Laboratory Medicine and 2Group of Infection Control Research, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Hamamatsu 431-3192; and 3Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. 1

References 1 Ooishi M, Miyao M. Antibiotic sensitivity of recent clinical isolates from patients with ocular infections. Ophthalmologica 1997; 211 (suppl. 1): 15–24. 2 Traore O, Fournet Fayard S, Laveran H. An in-vitro evaluation of the activity of povidone-iodine against nosocomial bacterial strains. J Hosp Infect 1996: 34: 217–222.

Letters to the Editor 3 Rutala WA, Stiegel MM, Sarubbi FA, Weber DJ. Susceptibility of antibiotic-susceptible and antibiotic-resistant hospital bacteria to disinfectants. Infect Control Hosp Epidemiol 1997; 18: 417–421. 4 Kampf G, Jarosch R, Ruden H. Limited effectiveness of chlorhexidine based hand disinfectants against methicillin-resistant Staphylococcus aureus (MRSA). J Hosp Infect 1998;38: 297–303. 5 Bosi C, Davin-Regli A, Charrel R, Rocca B, Monnet D, Bollet C. Serratia marcescens nosocomial outbreak due to contamination of hexetidine solution. J Hosp Infect 1996;33: 217–224.

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6 National Committee for Clinical Laboratory Standards. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically, 2nd ed. Approved Standard M7-A3. Villanova, PA: National Committee for Clinical Laboratory Standards; 1993. Accepted for publication 22 February 2001