E m e r g e n c e and control of methicillin.resistant Staphylococcus a u r e u s in a children's hospital and pediatric long-term c a r e facility Beth H. Stover, RN, ClC a Angela Duff, MD = Garrett Adams, MD, MPH b George Buck, PhD b Gary Hancock, BS c Gerard Rabalais, MD b Louisville, Kentucky
Background: After a 6-year quiescence, methicillin-resistant Staphyloccus aureus (MRSA) was isolated from 30 patients in a children's hospital and a pediatric long-term care facility from November 1987 through April 1989. After six nosocomial cases had occurred at the children's hospital, increased infection control measures directed at MRSA were initiated in August 1988. Because MRSA had been identified in three patients in the pediatric long-term care facility within 24 hours of their admission to the children's hospital, other patients transferred from the pediatric long-term care facility to the children's hospital were isolated and screened for MRSA. Methods: We reviewed the medical records of these patients and evaluated their response to therapy with rifampin alone or in combination with trimethoprim~sulfamethoxazole. Results: In the 8-month period after initiation of infection control measures, MRSA was identified in 10 residents of the pediatric long-term care facility; there was also one nosocomial children's hospital case. Phage typing showed that one MRSA strain predominated in patients at the pediatric long-term care facility but did not implicate this strain as the source for MRSA introduction into the children's hospital. Of 16 patients with MRSA who completed therapy and were available for follow-up, 13 (81%) had elimination of colonization. Conclusion: Prompt institution of MRSA surveillance, barrier isolation, and therapy to eliminate colonization should be considered in hospitals with a new introduction of MRSA. (AJIC AM J INFECTCONTgOL 1992;20:248-55)
Methicillin-resistant Staphylococcus aureus ( M R S A ) is b e i n g s e e n w i t h i n c r e a s e d f r e q u e n c y From Kosair Children's HospitaP and the University of Louisville School of Medicine, Department of Pediatrics, Division of Pecfiatric Infectious Diseases, b Louisville, Kentucky, and Centers for Disease Control, Hospital Infection Program, Atlanta, Georgia? Supported by a grant from the Department of Pediatrics Research Committee, University of Louisville School of Medicine, Louisville, Kentucky. Presented in part at the Twenty-ninth Interscience Conference on Antimicrobial Agents and Chemotherapy, Houston, Texas, September 17-20, 1989. Reprint requests: Beth H. Stover, RN, Infection Control, Kosair Children's Hospital, P.O. Box 35070, Louisville, KY 40232-5070.
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a s a n o s o c o m i a l p a t h o g e n . 1-s M R S A h a s b e e n reported from virtually all types of hospital, including children's hospitals. 4 Outbreaks of M R S A i n a d u l t l o n g - t e r m c a r e f a c i l i t i e s 8-1° h a v e been described. Hospital outbreaks of MRSA may occur after transfer of colonized patients from a long-term care facility to the hospital. 8 We describe here an outbreak of MRSA in a children's hospital in which a pediatric long-term care facility (PLCF) was considered a potential reservoir. Introduction of infection control measures coincided with reduced nosocomial transmission of MRSA. Most children were successfully freed of MRSA colonization with systemic antimicrobial therapy.
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METHODS
Kosair Children's .Hospital is a 227-bed tertiary care hospital affiliated with the University of Louisville. Admissions during 1988 totaled 8150, for 61,702 patient days. There were 45,533 outpatient clinic and emergency department visits. The children's hospital is affiliated w i t h a n adjacent 384-bed adult facility. Ancillary services, such as laboratory and respiratory therapy, are shared by the two facilities. The PLCF is a 40-bed intermediate and Skilied nursing care facility, separate from the children's hospital. Residents are admitted to the PLCF from the children's hospital, a local rehabilitation center, and acute care facilities from within and outside the state of Kentucky. A total of 75 short-term and long-term care patients resided in the PLCF during 1988. Length of stay ranged from 2 weeks to 7 years. Inpatient and outpatient medical services are provided to PLCF patients by the children's hospital. Data were not available regarding the number of PLCF inpatient or outpatient visits, nor for lengths of stay at the children's hospital during the study period. Staff were not shared by the two facilities. S. aureus was identified by standard methods of Gram staining, colony characteristics, and latexagglutination testing (Staphaurex; Burroughs Wellcome, Triangle Park, N.C.). 11 S. aureus susceptibility testing was performed by broth microdilution and oxacillin-plate screening. Fresh subcultures of each isolate (24 hours) were suspended in saline solution to the density of a 0.5 McFarland standard and then diluted in MuellerHinton broth to a final concentration 2 × 106 colony-forming units/ml. These suspensions were inoculated to a dehydrated tray (Sensititre; Sensititre Systems Group, Westlake, Ohio) containing oxacillin and 2% sodium chloride solution. The trays were incubated at 35 ° C for 18 to 24 hours, then read. A fresh subculture of each isolate (24 hours), suspended in saline solution to the density of a 0.5 McFarland standard, was spotted onto a plate of Mueller-Hinton agar containing 4% sodium chloride solution and 6 ~g/ml oxacillin. The plates were incubated at 35 ° C for 24 hours and examined for growth. Interpretation was based on nationally recommended standards. 12,13Susceptibilities to antibiotics other than oxacillin w e r e determined by the agar disc diffusion method. Phage typing was performed by the Hospital Infections Program, Centers for Disease Control (CDC). Bacteriophages used included the following: group I - 29, 52, 52A, 79, and 80; group
MRSA in a childrens' hospital 2 4 9
II 3A, 3C, 55, and 7A; group III 6, 42E, 47, 53, 54, 75, 77, 83A, 84 and 85; group V 94 arid 96~ and phages 81 and 95, not allocated to a group. A case of MRSA was defined as isolation of MRSA from any body site of an inpatient or outpatient, from November 1987 through April 1989. Cases were identified through daily review of microbiology reports. MRSA was designated as c o m m u n i t y acquired if the patient had not been a resident at the PLCF nor previously hospitalized at the children's hospital. MRSA cases were designated PLCF associated if the patient resided at the PLCF and nosocomial acquisition at the children's hospital was ruled out by previous cultures negative for MRSA. Cases of MRSA were identified as nosocomially acquired if the patient had been hospitalized at the children's hospital since birth, the patient had not resided at the PLCF, or the CDC Disease Control definitions for nosocomial infection 14 were met and MRSA had not been isolated previously from any body site. The CDC definitions for nosocomial infection were used to define nos0comial hospital infection. Patient records were reviewed for sex, age, underlying disease or condition, sites of colonization, evidence of infection, antimicrobial therapy, hospital admissions, and outpatient visits. Nares, skin, wounds, surgical incisions, and invasive device sites were cultured. When surveillance culture samples were obtained, a sterile cotton-tipped applicator was moistened with trypticase soy broth. The culture site was swabbed with the moistened applicator in multiple strokes; this was followed by rolling the applicator in 0.5 ml of trypticase soy broth. Specimens were plated onto a phenylethyl alcohol selective medium to enhance isolation of",S, aureus. Isolation for MRSA was accomplished by following the CDC disease-specific isolation precautions, is Additional infection control measures were instituted in August 1988 for case recognition, patient isolation, and colonization elimination therapy (Table 1). It was recommended that all children colonized with MRSA be treated with a regimen of trimethoprim-sulfamethoxazole and rifampin. RESULTS
Betwe&n November 1987 and April 1989, the microbiology laboratory identified MRSA in cultures from 30 children (Fig. 1). Eighteen cases were PLCF associated, seven were nosocomiaUy acquired, and five were community acquired. Six nosocomial cases met criteria for nosocomial
250
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MRSA infection. MRSA had not been isolated in these six patients before the infection episode. After a 6-year period during which MRSA was not isolated from our pediatric population, in November of 1987 MRSA was cultured from the scalp lesion of a PLCF resident. By August 1988, MRSA had been isolated from 12 children. Three of five PLCF patients with MRSA had been hospitalized during the time when nosocomial MRSA occurred at children's hospital, June and July 1988. The PLCF patients were considered a possible source of:the introduction of MRSA into the children's hospital. Beginning in August 1988, all subsequent patients admitted to Kosair Children's Hospital from the PLCF were isolated a n d screened for MRSA colonization (Table 1). Colonization elimination therapy was initiated at the discretion of each patient's primary physician. Additional~ surveillance culture samples from patients were obtained in two instances. In August 1988, after three nosocomial MRSA cases had occurred on a single medical-surgical unit, screening culture samples were obtained from the 15 patients in that unit. All patients known to be colonized with MRSA were excluded. No additional cases of MRSA colonization were identified. No additional nosocomial cases occurred on that unit during the study period: Because ! 6 patients from whom MRSA h a d ' b e e n recovered were residents of the PLCF, we did a cfilture survey of all 42 PLCF residents at their institution in April
1989. Two previously unknown cases of MRSA colonization were then identified (Fig. 1). The 30 patients with MRSA ranged in age from 7 days to 15 years (mean, 3.5 years; median, 2 years). Twenty-seven patients had multiple chronic medical illnesses including neurologic defects (18 patients), premature birth (14 patients), congenital heart disease (5 patients), chronic pulmonary disease (7 patients), renal disease (4 patients), malabsorption problems (3 patients), and other chronic illnesses (9 patients). The sites of MRSA colonization included nares (nine patients), invasive device sites (eight patients), wounds (seven patients), eyes (three patients), skin (two patients), and other body sites (six patients). The antimicrobial-resistance pattern of MRSA isolates from 29 patients is shown in Table 2. Isolates from five of 29 patients were resistant to trimethoprim-sulfamethoxazole. The initial MRSA isolates from three patients were resistant to trimethoprim-sulfamethoxazole. In two cases trimethoprim sulfamethoxazole-resistant MRSA was recovered after antimicrobial therapy was started. Of 12 MRSA isolates tested, two were rifampin resistant. One of these was identified before colonization elimination therapy and the second was recovered from a patient after multiple courses of rifampin and trimethoprimsulfamethoxazole. Phage typing of MRSA was done in two batches
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T a b l e 1. Infection control measures at Kosair Children's Hospital, August 1988 " 1. Patients transferred from any facility known to have MRSA and any new admission in whom MRSA has been identified require: A. Isolation: private room; gown and gloves for patient contact; and masks or goggles when likely that eyes or mucous membranes will be splashed ("resistant organism precautions") B. MRSA surveillance cultures: 1. Nares 2. Skin; axilla to groin 3. Exit site or secretions from any invasive device 4. Skin lesions C, Maintain isolation until surveillance cultures reported negative for MRSA 2. Consider decolonization therapy for patients in whom MRSA is identified: Rifampin 20 mg/kg every 24 hours in two divided doses, plus trimethoprimsulfamethoxazole (10 mg trimethoprim component/kg per 24 hours in two divided doses) 3. Treat invasive disease with vancomycin
containing isolates from 19 patients (Table 3). Phage typing of the first batch of 16 MRSA isolates revealed phage 54/75/77/83A as c o m m o n to PLCF residents. The second batch of MRSA isolates revealed phage 47/54/75/83A in two PLCF residents. OnlY five nosocomial and three c o m m u n i t y MRSA strains were available for phage typing; nosocomial and c o m m u n i t y MRSA isolates either were not typable or were different from the PLCF isolates. Colonization elimination therapy, with rifampin, trimethoprim-sulfamethoxazole, or both, was attempted in 20 patients. F o u r patients were unavailable for follow-up. Overall, 13 of the remaining 16 patients had successful elimination of colonization (Fig. 2). Of these 13 patients, 11 h a d no MRSA after one course; two patient, s required two courses of therapy. Elimination of colonization in patients with gastrostomies and tracheostomies was problematic. Of the three patients in w h o m colonization was not eliminated, two had tracheal colonization and all had colonization of the gastrostomy tube site. We were unable to eradicate MRSA from either the gastrostomy tube site or from the tracheal secretions of these three patients. One patient with a gastrostomy tube and tracheostomy (patient 17, Fig. 2) had colonization of the nares and the gastrostomy tube site. After two courses of therapy colonization had been eradicated, but this patient had recurrence of MRSA several months
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T a b l e 2 . MRSA antimicrobial resistance pattern
Antibiotic
Tested*
Trimethoprim-sulfamethoxazole Gentamicin Erythromycin Tetracycline Chloramphenicol Clindamycin Rifampin
29 29 29 29 28 29 12
Resistant n % 5 13 27 2 1 19 2
~17,2 44.8 93.1 6.9 3.6 64.5 16.6
*One isolatewas tested only for oxacillinsusceptibility.
after the study period concluded. Colonization was eliminated in two patients with gastrostomy tube site colonization (patients 19 and 25, Fig. 2). DISCUSSION
Some physicians question the need for expensive and disruptive infection control measures directed at limiting MRSA transmission, 16 whereas others advocate controls. Is'17'ls For three reasons, we believe that MRSA should be considered a serious nosocomial problem and some attempt should be made to control its spread. First, the widespread hospital-to-community outbreaks of penicillin-resistant S. aureus infection that occurred from 1946 to 196619 have not been forgotten. It is interesting to note that all patients whose cases met our definition for c o m m u n i t y acquired MRSA had been outpatients at the children's hospital, a rehabilitation center, or outpatient clinics witifin 6 months of MRSA identification. In these cases, MRSA m a y have been associated with outpatient facility contact rather than actually being community acquired. MRSA colonization is usually associated with inpatient hospitalization, and ordinarily is not expected among individuals with only brief outpatient visits. Such potential spread of MRSA into the community would significantly complicate the outpatient m a n a g e m e n t of infection, which usually consists of treatment with oral antimicrobials active against methicillin-susceptible S. aureus. Second, MRSA has become an important cause of nosocomial outbreaks in hospitals and extended care facilities. 5'9'1°'17'2° In hospitals, as many as 30% to 60% of patients colonized with MRSA later have infection. 17 Third, even though MRSA appears to be no m o r e pathogenic than methicillinsusceptible S. aureus,16 the r e c o m m e n d e d antimicrobial agent for treatment of serious MRSA
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infections is intravenous vancomycin.17 Vancomycin is both more expensive and more toxic than are the drugs used to treat methicillin-susceptible S. a u r e u s . Resistance to vancomycin has been noted in other bacteria, 2~-24 and there is concern that such resistance m a y develop in MRSA. We elected to institute MRSA infection control measures at our hospital in August 1988 because this outbreak represented a n e w introduction of MRSA. This rationale was cited in a recent review 6 of this topic as one circumstance that may w a r r a n t special infection control measures. Boyce 6 reported that the rapid institution of infection control measures w h e n MRSA is first introduced into the hospital is supported by the fact that of 46 published outbreak reports, all 11 hospitals with fewer than 20 cases achieved definite or probable eradication of MRSA; this compares with a 71% success rate in hospitals with 20 to 39 cases and a success rate of only 10% in hospitals with 40 or more cases. In addition to increased surveillance and isolation, we also elected to eradicate colonization from patients with systemic antimicrobial therapy. The reported effectiveness of such therapy is variable. 25-32Our p r i m a r y reason for the use of such a regimen was to reduce the MRSA microbial b u r d e n on the host. We realized that complete eradication of MRSA might not be
possible, but we hoped that by decreasing the reservoir nosocomial transmission of MRSA and subsequent infections might be reduced. To our knowledge, only one study examines the success of elimination of MRSA colonization in the pediatric population, a3 In that study topical mupirocin and 0.3% hexachlorophane p o w d e r were used t o t r e a t 12 infants in a special care bal3y unit. Five of these infants were reported to have recurrence of colonization. Our apparent success in eliminating colonization parallels that of previous studies in adult patients, but our data must be interpreted in the absence of a control group and our lack of knowledge about the natural history of MRSA colonization. Rao and coworkers 3° used a combination of rifampin, bacitracin ointment, and chlorhexidine showers for 7 days in 16 patients. Cultures from 56% of these patients were negative for MRSA at 7 days after therapy. Roccaforte and associates 3] reported successful eradication with trimethoprim-sulfamethoxazole plus rifampin and bacitracin ointment applied to the nares in 40 of 47 patients; however, relapse occurred in nine patients. Mean duration of treatment was 6.0 _ 2.4 days. Winn and associates 34 were successful in eliminating colonization in 10 of 12 patients with nasal and extranasal MRSA with rifampin, trimethoprim-sulfamethoxazole,
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T a b l e 3. Suspected source, clinical site, antimicrobial resistance, and phage typing of MRSA in 19 patients whose isolates were available for phage typing Pt.
MRSA Source
Site
Antlmicrobial resistance
2 3 4 7 8 10 9 13 14 17 18 6 15 26 21 28 29 30 5
N N PLCF N CA N PLCF N PLCF PLCF PLCF PLCF PLCF PLCF CA CA PLCF PLCF PLCF
Throat Eye Foot Sputum Sputum Back tissue Wound Peritoneal Fluid Nasopharynx Gastrostomy tube Axilla Urine Nasopharynx Nasopharynx Wound Urine Nares Gastrostomy tube Gastrostomy tube
EES, GEN, IMIP, TMP-SX EES, GEN CHLORQ, CLD, EES, IMIP EES, GEN EES, GEN EES CLD EES, IMIP EES GEN CLD EES CLD EES, IMIP CLD EES CLD EES CLD EES, IMIP, RIF CLD EES, IMIP EES TETRA CLD, EES, GEN, TMP-SX No other testing EES, GEN, IMIP CLD, EES, RIF
Phage type (100 x RTD) NR NR 54/75/77/83A 75 75 6/54/75/77/83A/81 54/75/77/83A 75 54/75/77/83A 54/75/77/83A 54/75/77/83A 54/75/77/83A 54/75/77/83A 54/75/77/83A NR 80* 47/54/75/83A 75 47/54/75/83A
Isolatesfrom patients5, 28, 29, and 30 werephagetypedas a separatebatch. RTD,Routinetest dilution;N, nosocomial;EES,erythromycin;GEN,gentamlcin; IMIP, irnipenem; TMP-SX,trimethoprim-sulfamethoxazole;NR, not recorded; CHLORO, chloramphenicol; CLD, clindamycin; CA, community acquired; RIF, rifampin; TETRA,tetracycline. *Phage group I; all others reactedin phage group III.
and intranasal bacitracin for 5 days. Ellison and colleaguess2 used 5 days of rifampin plus trimethoprim-sulfamethoxazolein 14 patients and staff members. Eight of 12 persons had elimination of colonization with initial therapy; however, two patients later had recurrences. Extranasal colonization, especially in the presence of foreign bodies, has been associated with failure to eradicate MRSA. a~ Winn and associates 34 reported treatment failure in three patients with wound and nares colonization when rifampin was used with bacitracin for 5 days. In the study of Roccaforte and coworkers, aj 4 of 22 patients with extranasal colonization had treatment failure. In our patients, treatment failure was more common among patients with gastrostomy tubes and tracheostomies; however, two of three patients in this group were colonized with rifampin-resistant organisms. It is not clear what effects each of these factors had on failure to eliminate colonization. Resistance of MRSA at our institution to multiple antibiotics is consistent with the patterns described by others, a*-a6 Rifampin resistance has been observed during therapy, s4"aT"aa Bitar and co]leagues26 reported an outbreak of rifampinresistant MRSA among hospitalized adults. MRSA strains resistant to both rifampin and
trimethoprim-sulfamethoxazole have also been reported, sg"*° Emergence of rifampin and trimethoprim-sulfamethoxazole resistance in MRSA necessitates the testing of MRSA strains for susceptibility to these drugs when elimination of colonization is considered. Most reported outbreaks of MRSA have been associated with a predominant strain, although more than one strain may be present. 9'25'2s Bacteriophage typing has been a standard epidemiologic tool in the evaluation of S. a u r e u s outbreaks. However, recent studies have shown that phage typing of MRSA isolates is less reliable than plasmid analysis. 41,42 In this outbreak, a phage type common to the PLCF was identified in the eight PLCF patient isolates tested in the first batch. The three PLCF isolates in the second batch were different from those identified in the first batch (Table 3). Discordant phage type results seen in the PLCF isolates tested in the second group may have been related to lack of reproducibility or to instability of the isolates. We believe that phage typing can be a useful epidemiologic tool; however, we suggest that all MRSA isolates undergo testing in one batch. In the 2 years since the conclusion of this study, 2 1 new case~ of MRSA have been identified among our pediatric patients. Five of these cases met our
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definition as c o m m u n i t y - a c q u i r e d cases. One patient w a s t r a n s f e r r e d f r o m a n o t h e r a c u t e c a r e facility to the c h i l d r e n ' s hospital. E l e v e n n o s o c o mial cases h a v e o c c u r r e d in the c h i l d r e n ' s hospital. These h a v e b e e n c o n f i n e d to several timea s s o c i a t e d clusters in the n e o n a t a l intensive c a r e unit. B e c a u s e of u n k n o w n effects of r i f a m p i n a n d t r i m e t h o p r i m - s u l f a m e t h o x a z o l e in neonates, use of these a g e n t s in this p o p u l a t i o n has b e e n limited. P L C F patients c o l o n i z e d w i t h M R S A r e m a i n in isolation at the PLCF. Patients t r a n s f e r r e d f r o m the P L C F or o t h e r l o n g - t e r m c a r e facilities c o n tinue to be p l a c e d in isolation o n a d m i s s i o n to the c h i l d r e n ' s hospital, a n d s u r v e i l l a n c e culture s a m ples are obtained. I s o l a t i o n is c o n t i n u e d if M R S A is identified. P r e v i o u s l y identified M R S A cases are flagged in the hospital c o m p u t e r , a n d patients are isolated if r e a d m i t t e d . T h e r a p y to eliminate colon i z a t i o n is n o w d i r e c t e d t o w a r d patients w h o s e u n d e r l y i n g c o n d i t i o n r e q u i r e s l o n g - t e r m hospitalization o r t h o s e w h o a r e r e s i d e n t s of a l o n g - t e r m c a r e facility. W e believe that o u r infection c o n t r o l a n d c o l o n i z a t i o n e l i m i n a t i o n efforts have b e e n successful. N o s o c o m i a l cases h a v e b e e n limited to one unit, the n e o n a t a l intensive c a r e unit; the original s o u r c e for i n t r o d u c t i o n of M R S A to this unit has n o t b e e n identified. Despite multiple hospital a d m i s s i o n s of P L C F patients c o l o n i z e d with M R S A a n d a d m i s s i o n s of patients w i t h c o m m u n i t y - a c q u i r e d MRSA, n o s o c o m i a l t r a n s m i s s i o n has n o t b e e n a s s o c i a t e d with these patients. To o u r k n o w l e d g e , this is the first r e p o r t of M R S A a s s o c i a t e d w i t h a PLCF. The P L C F c o u l d n o t be c o n f i r m e d as the s o u r c e of i n t r o d u c t i o n of M R S A into the c h i l d r e n ' s hospital. P r o m p t institution of M R S A surveillance, b a r r i e r isolation, a n d t h e r a p y to e l i m i n a t e c o l o n i z a t i o n in p a t i e n t s s h o u l d be c o n s i d e r e d in hospitals with a n e w i n t r o d u c t i o n o f MRSA. We thank the staffs of both the pediatric long-term care facility and Kosair Children's Hospital for their cooperation in this effort to reduce MRSA transmission, and we thank Beverly Beckman for her secretarial assistance. References
1. Haley RW, Hightower AW, Khabbaz RF, et al. The emergence of methicillin-resistant Staphylococcus aureus infections in United States hospitals. Ann Intern Med 1983;97:297-308. 2. Boyce JM, Causey WA. Increasing occurrence of methicillin-resistant Staphylococcus aureus in the United States. Infect Control 1982;3:377-83. 3. Casewell MW. Epidemiology and control of the "modern"
AJIC October 1992
methicillin-resistant Staphylococcus aureus. J Hosp Infect 1986;7(Suppt A):I-I 1: 4. Jarvis WR, Thornsberry C, Boyce J, Hughes JM. Methicinin-resistant Staphylococcus aureus at children's hospitals in the United States. Pediatr Infect Dis 1985;4: 651-5. 5. Boyce JM. Increasing prevalence of methicinin-resistant Staphylococcus aureus in the United States. Infect Control Hosp Epidemiol 1990;11:639-42. 6. Boyce JM. Should we vigorously try to contain and control methicinin-resistant Staphylococcus aureus? Infect Control Hosp Epidemiol 1991;12:46-54. 7. Thompson RL, Caberzuda I, Wenzel PP. Epidemiology of nosocomial infections caused by mcthiciIlin-resistant Staphylococcus aureus. Ann Intern Med 1982;97:309-17. 8. O'Toole RD, Drew WL, Dahlgren BJ, et al. An outbreak of methicillin-resistant Staphylococcus aureus infection. Observations in hospital and nursing home. JAMA 1970;213: 257-63. 9. Storeh GA, Radcliff JL, Meyer PL, Hinrichs JH. Methicillin-resistant Staphylococcus aureus in a nursing home. Infect Control 1987;8:24-9. 10. Thomas JC, Bridges J, Water S, Vogt J, Kilman L, Hancock G. Transmission of and Control of methicillin-resistant Staphylococcus aureus in a skilled nursing facility. Infect Control Hosp Epidemiol 1989;10:106-10. 11. Lairscey R, Buck GE. Performance of four slide agglutination methods for identification of Staphylococcus aureus when testing methicillin-resistant staphylococci. J Clin Microbiol 1987;25:181-2. 12. McDougal LK, Thornsberry C. New recommendations for disk diffusion antimicrobial susceptibility tests for methicinin-resistant (heteroresistant) staphylococci. J Clin Microbiol 1984;19:482-8. 13. National Committee for Clinical Laboratory Standards. Performance standards for antimicrobic disc susceptibility tests. Villanova, Pennsylvania: National Committee for Clinical Laboratory Standards, 1979. 14. Garner JS, Jarvis WR, Emori TG, Horma TC, Hughes JM. CDC definitions for nosocomial infection. Infect Control 1988;16:138-40. 15. Garner JS, Simmons BP. Guideline for isolation precautions in hospitals. Infect Control 1983;4(4 Suppl):245-325. 16. McManus AT, Mason AD, Pruit BA. What's in a name? Is methicinin-resistant Staphylococcus aureus just another S. aureus when treated with vancomycin? Arch Surg 1989; 124:1456-9. 17. Boyce JM. Methicillin-resistant Staphylococcus aureus detection, epidemiology, and control measures. Infect Dis Clinics North Am 1989;3:901-914. 18. Standiford HC. Methicillin-resistant Staphylococcus aureus infections: it's time to get tough. Infect Control 1987;8:187-9. 19. Wise RI, Ossman EA, Littlefield DR. Personal reflections on nosocomial staphylococcal infections and the development of hospital surveillance. Rev Infect Dis 1989;11: 1005-19. 20. Kauffman CA, Bradley SF, Terpenning MS. Methicillinresistant Staphylococcus aureus in long-term care facilities. Infect Control Hosp Epidemiol 1990;11:600-3. 21. Sanyal D, Johnson AP, Georg RC, Cookson BD, Williams AJ. Peritonitis due to vancomycin-resistant Staphylococcus epidermidis [Letter]. Lancet 1991;337:54. 22. Veach LA, Pfaller MA, Barnett M, Koontz FP, Wenzel PP.
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Vancomycin resistance in Staphylococcus haemolyticus causing colonization and bloodstream infection. J Clin Microbiol 1990;28:2064-8. 23. Johnson AP, Uttley AH, Woodford N, George RC. Resistance to vancomycin and teicoplanin: an emerging clinical problem. Clin Microbiol Rev 1990;3:280-91. 24. Kaplan AH, Gilligan PH, Facklam RR. Recovery of resistant enterococci during vancomycin prophylaxis. J Clin Microbiol 1988;26:1216-8. 25. Ward Tr, Winn RE, Hartstain AL, et al. Observations relating to an interhospital outbreak of methicillinresistant Staphylococcus aureus: role, of antimicrobial therapy in infection control. Infect Control 1981;2:453-9. 26. Bitar CM, Mayhall CG, Lamb VA, et al. Outbreak due to methicillin- and rifampin-resistant Staphylococcus aureus: epidemiology and eradication of the resistant strain from the hospital. Infect Control 1987;8:15-23. 27. Dacre JE, Emmerson AM, Jenner EA. Nasal carriage of gentamicin and methicillin-resistant Staphylococcus aureus treated with topical pseudomonic acid [Letter]. Lancet 1983;2:1036. 28. Bacon AE, Jorgensen KA, Wilson KH, Kauffman CA. Emergence of nosocomial methicillin-resistant Staphylococcus aureus and therapy of colonized personnel during a hospital-wide outbreak. Infect Control 1987;8:145-50. 29. Denning DW, Haiduven-Griftith D. Eradication of lowlevel methicillin-resistantStaphylococcus aureus skin colonization with topical mupirocin. Infect Control Hosp Epidemiol 1988;9:261-3. 30. Rao N, Jacobs S, Joyce L. Cost-effective eradication of an outbreak of methicillin-resistantStaphylococcus aureus in a community teaching hospital. Infect Control Hosp Epidemiol 1988;9:255-60. 31. Roccaforte JS, Bittner MJ, Stumpf CA, Preheim LC. Attempts to eradicate methicillin-resistantStaphylococcus aureus colonization with the use of trimethoprimsulfamethoxazole, rifampin and bacitracin. AM J INFECT CONTROL 1988;16:141-5. 32. Ellison RT, Judson FN, Peterson LC, et al. Oral rifampin and trimethoprim/sulfa-methoxazole therapy in asymptomatic carriers of methicillin-resistant Staphylococcus aureus infections. West J Med 1984;140:735-40.
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33. Davies EA, Emmerson AM, Hogg GM, Patterson MF, Shield MD. An outbreak of infection with a methicillinresistant Staphylococcus aureus in a special care baby unit: value of topical mupirocin and of traditional methods of infection control. J Hosp Infect 1987;10:120-8. 34. Winn RE, Ward TF, Hartstein AI, et al. Epidemiological, bacteriological, and clinical observations on an interhospital outbreak of nafcillin-resistantStaphylococcus aureus. In: Nelson JD, Grassi D, eds. Current chemotherapy and infectious diseases, vol 2. Washington, DC: American Society for Microbiology, 1980:1096-7. 35. Richmond A, Simberkoff M, Schaefler S, et al. Resistance of Staphylococcus aureus to semisynthetic penicillins and cephalothin. J Infect Dis 1977;135:108-12. 36. Brumfitt W, Hamilton-Miller J. Methicillin-resistant Staphylococcus aureus. N Engl J Med 1989;320:118896. 37. Eng RH, Smith SM, Tillen M, Cherubin C. Rifampin resistance development during the therapy of methicillinresistant Staphylococcus aureus infection. Arch Intern Med 1985;145:146-8. 38. Simon GL, Smith RH, Sande MA. Emergence of rifampinresistant strains of Staphylococcus aureus during combination therapy with vancomycin and rifarnpin: a report of two cases. Rev Infect Dis 1983;5(Suppl 3):$507-8. 39. Coovadia YM, Bhana RH, Johnson AP, Haffejee I, Marples RR. A laboratory confirmed outbreak of rifampinmethicillin resistant Staphylococcus aureus MRSA in a newborn nursery. J Hosp Infect 1989;14:303-12. 40. Ruane DJ, Morgan MA, Citron DM, Mulligan ME. Failure of rapid agglutination methods to detect oxacillin-resistant Staphylococcus aureus. J Clin Microbiol 1986;24:490-2. 41. Rhinehart E, Shlaes DM, Keys TF, et al. Nosocomial clonal dissemination of methicillin-resistant Staphylococcus aureus: elucidation by plasmid analysis. Arch Intern Med 1987;147:521-4. 42. Archer GL, Mayhall CG. Comparison of epidemiological markers used in the investigation of an outbreak of methicillin-resistant Staphylococcus aureus infections. J Clin Microbiol 1983;18:395-9.
Background: After a 6-year quiescence, methicillin-resistant Staphyloccus aureus (MRSA) was isolated from 30 patients in a children's hospital and a pediatric long-term care facility from November 1987 through April 1989. After six nosocomial cases had occurred at the children's hospital, increased infection control measures directed at MRSA were initiated in August 1988. Because MRSA had been identified in three patients in the pediatric long-term care facility within 24 hours of their admission to the children's hospital, other patients transferred from the pediatric long-term care facility to the children's hospital were isolated and screened for MRSA. Methods: We reviewed the medical records of these patients and evaluated their response to therapy with rifampin alone or in combination with trimethoprim~sulfamethoxazole. Results: In the 8-month period after initiation of infection control measures, MRSA was identified in 10 residents of the pediatric long-term care facility; there was also one nosocomial children's hospital case. Phage typing showed that one MRSA strain predominated in patients at the pediatric long-term care facility but did not implicate this strain as the source for MRSA introduction into the children's hospital. Of 16 patients with MRSA who completed therapy and were available for follow-up, 13 (81%) had elimination of colonization. Conclusion: Prompt institution of MRSA surveillance, barrier isolation, and therapy to eliminate colonization should be considered in hospitals with a new introduction of MRSA. (AJIC AM J INFECTCONTgOL 1992;20:248-55)
Methicillin-resistant Staphylococcus aureus ( M R S A ) is b e i n g s e e n w i t h i n c r e a s e d f r e q u e n c y From Kosair Children's HospitaP and the University of Louisville School of Medicine, Department of Pediatrics, Division of Pecfiatric Infectious Diseases, b Louisville, Kentucky, and Centers for Disease Control, Hospital Infection Program, Atlanta, Georgia? Supported by a grant from the Department of Pediatrics Research Committee, University of Louisville School of Medicine, Louisville, Kentucky. Presented in part at the Twenty-ninth Interscience Conference on Antimicrobial Agents and Chemotherapy, Houston, Texas, September 17-20, 1989. Reprint requests: Beth H. Stover, RN, Infection Control, Kosair Children's Hospital, P.O. Box 35070, Louisville, KY 40232-5070.
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a s a n o s o c o m i a l p a t h o g e n . 1-s M R S A h a s b e e n reported from virtually all types of hospital, including children's hospitals. 4 Outbreaks of M R S A i n a d u l t l o n g - t e r m c a r e f a c i l i t i e s 8-1° h a v e been described. Hospital outbreaks of MRSA may occur after transfer of colonized patients from a long-term care facility to the hospital. 8 We describe here an outbreak of MRSA in a children's hospital in which a pediatric long-term care facility (PLCF) was considered a potential reservoir. Introduction of infection control measures coincided with reduced nosocomial transmission of MRSA. Most children were successfully freed of MRSA colonization with systemic antimicrobial therapy.
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METHODS
Kosair Children's .Hospital is a 227-bed tertiary care hospital affiliated with the University of Louisville. Admissions during 1988 totaled 8150, for 61,702 patient days. There were 45,533 outpatient clinic and emergency department visits. The children's hospital is affiliated w i t h a n adjacent 384-bed adult facility. Ancillary services, such as laboratory and respiratory therapy, are shared by the two facilities. The PLCF is a 40-bed intermediate and Skilied nursing care facility, separate from the children's hospital. Residents are admitted to the PLCF from the children's hospital, a local rehabilitation center, and acute care facilities from within and outside the state of Kentucky. A total of 75 short-term and long-term care patients resided in the PLCF during 1988. Length of stay ranged from 2 weeks to 7 years. Inpatient and outpatient medical services are provided to PLCF patients by the children's hospital. Data were not available regarding the number of PLCF inpatient or outpatient visits, nor for lengths of stay at the children's hospital during the study period. Staff were not shared by the two facilities. S. aureus was identified by standard methods of Gram staining, colony characteristics, and latexagglutination testing (Staphaurex; Burroughs Wellcome, Triangle Park, N.C.). 11 S. aureus susceptibility testing was performed by broth microdilution and oxacillin-plate screening. Fresh subcultures of each isolate (24 hours) were suspended in saline solution to the density of a 0.5 McFarland standard and then diluted in MuellerHinton broth to a final concentration 2 × 106 colony-forming units/ml. These suspensions were inoculated to a dehydrated tray (Sensititre; Sensititre Systems Group, Westlake, Ohio) containing oxacillin and 2% sodium chloride solution. The trays were incubated at 35 ° C for 18 to 24 hours, then read. A fresh subculture of each isolate (24 hours), suspended in saline solution to the density of a 0.5 McFarland standard, was spotted onto a plate of Mueller-Hinton agar containing 4% sodium chloride solution and 6 ~g/ml oxacillin. The plates were incubated at 35 ° C for 24 hours and examined for growth. Interpretation was based on nationally recommended standards. 12,13Susceptibilities to antibiotics other than oxacillin w e r e determined by the agar disc diffusion method. Phage typing was performed by the Hospital Infections Program, Centers for Disease Control (CDC). Bacteriophages used included the following: group I - 29, 52, 52A, 79, and 80; group
MRSA in a childrens' hospital 2 4 9
II 3A, 3C, 55, and 7A; group III 6, 42E, 47, 53, 54, 75, 77, 83A, 84 and 85; group V 94 arid 96~ and phages 81 and 95, not allocated to a group. A case of MRSA was defined as isolation of MRSA from any body site of an inpatient or outpatient, from November 1987 through April 1989. Cases were identified through daily review of microbiology reports. MRSA was designated as c o m m u n i t y acquired if the patient had not been a resident at the PLCF nor previously hospitalized at the children's hospital. MRSA cases were designated PLCF associated if the patient resided at the PLCF and nosocomial acquisition at the children's hospital was ruled out by previous cultures negative for MRSA. Cases of MRSA were identified as nosocomially acquired if the patient had been hospitalized at the children's hospital since birth, the patient had not resided at the PLCF, or the CDC Disease Control definitions for nosocomial infection 14 were met and MRSA had not been isolated previously from any body site. The CDC definitions for nosocomial infection were used to define nos0comial hospital infection. Patient records were reviewed for sex, age, underlying disease or condition, sites of colonization, evidence of infection, antimicrobial therapy, hospital admissions, and outpatient visits. Nares, skin, wounds, surgical incisions, and invasive device sites were cultured. When surveillance culture samples were obtained, a sterile cotton-tipped applicator was moistened with trypticase soy broth. The culture site was swabbed with the moistened applicator in multiple strokes; this was followed by rolling the applicator in 0.5 ml of trypticase soy broth. Specimens were plated onto a phenylethyl alcohol selective medium to enhance isolation of",S, aureus. Isolation for MRSA was accomplished by following the CDC disease-specific isolation precautions, is Additional infection control measures were instituted in August 1988 for case recognition, patient isolation, and colonization elimination therapy (Table 1). It was recommended that all children colonized with MRSA be treated with a regimen of trimethoprim-sulfamethoxazole and rifampin. RESULTS
Betwe&n November 1987 and April 1989, the microbiology laboratory identified MRSA in cultures from 30 children (Fig. 1). Eighteen cases were PLCF associated, seven were nosocomiaUy acquired, and five were community acquired. Six nosocomial cases met criteria for nosocomial
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MRSA infection. MRSA had not been isolated in these six patients before the infection episode. After a 6-year period during which MRSA was not isolated from our pediatric population, in November of 1987 MRSA was cultured from the scalp lesion of a PLCF resident. By August 1988, MRSA had been isolated from 12 children. Three of five PLCF patients with MRSA had been hospitalized during the time when nosocomial MRSA occurred at children's hospital, June and July 1988. The PLCF patients were considered a possible source of:the introduction of MRSA into the children's hospital. Beginning in August 1988, all subsequent patients admitted to Kosair Children's Hospital from the PLCF were isolated a n d screened for MRSA colonization (Table 1). Colonization elimination therapy was initiated at the discretion of each patient's primary physician. Additional~ surveillance culture samples from patients were obtained in two instances. In August 1988, after three nosocomial MRSA cases had occurred on a single medical-surgical unit, screening culture samples were obtained from the 15 patients in that unit. All patients known to be colonized with MRSA were excluded. No additional cases of MRSA colonization were identified. No additional nosocomial cases occurred on that unit during the study period: Because ! 6 patients from whom MRSA h a d ' b e e n recovered were residents of the PLCF, we did a cfilture survey of all 42 PLCF residents at their institution in April
1989. Two previously unknown cases of MRSA colonization were then identified (Fig. 1). The 30 patients with MRSA ranged in age from 7 days to 15 years (mean, 3.5 years; median, 2 years). Twenty-seven patients had multiple chronic medical illnesses including neurologic defects (18 patients), premature birth (14 patients), congenital heart disease (5 patients), chronic pulmonary disease (7 patients), renal disease (4 patients), malabsorption problems (3 patients), and other chronic illnesses (9 patients). The sites of MRSA colonization included nares (nine patients), invasive device sites (eight patients), wounds (seven patients), eyes (three patients), skin (two patients), and other body sites (six patients). The antimicrobial-resistance pattern of MRSA isolates from 29 patients is shown in Table 2. Isolates from five of 29 patients were resistant to trimethoprim-sulfamethoxazole. The initial MRSA isolates from three patients were resistant to trimethoprim-sulfamethoxazole. In two cases trimethoprim sulfamethoxazole-resistant MRSA was recovered after antimicrobial therapy was started. Of 12 MRSA isolates tested, two were rifampin resistant. One of these was identified before colonization elimination therapy and the second was recovered from a patient after multiple courses of rifampin and trimethoprimsulfamethoxazole. Phage typing of MRSA was done in two batches
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T a b l e 1. Infection control measures at Kosair Children's Hospital, August 1988 " 1. Patients transferred from any facility known to have MRSA and any new admission in whom MRSA has been identified require: A. Isolation: private room; gown and gloves for patient contact; and masks or goggles when likely that eyes or mucous membranes will be splashed ("resistant organism precautions") B. MRSA surveillance cultures: 1. Nares 2. Skin; axilla to groin 3. Exit site or secretions from any invasive device 4. Skin lesions C, Maintain isolation until surveillance cultures reported negative for MRSA 2. Consider decolonization therapy for patients in whom MRSA is identified: Rifampin 20 mg/kg every 24 hours in two divided doses, plus trimethoprimsulfamethoxazole (10 mg trimethoprim component/kg per 24 hours in two divided doses) 3. Treat invasive disease with vancomycin
containing isolates from 19 patients (Table 3). Phage typing of the first batch of 16 MRSA isolates revealed phage 54/75/77/83A as c o m m o n to PLCF residents. The second batch of MRSA isolates revealed phage 47/54/75/83A in two PLCF residents. OnlY five nosocomial and three c o m m u n i t y MRSA strains were available for phage typing; nosocomial and c o m m u n i t y MRSA isolates either were not typable or were different from the PLCF isolates. Colonization elimination therapy, with rifampin, trimethoprim-sulfamethoxazole, or both, was attempted in 20 patients. F o u r patients were unavailable for follow-up. Overall, 13 of the remaining 16 patients had successful elimination of colonization (Fig. 2). Of these 13 patients, 11 h a d no MRSA after one course; two patient, s required two courses of therapy. Elimination of colonization in patients with gastrostomies and tracheostomies was problematic. Of the three patients in w h o m colonization was not eliminated, two had tracheal colonization and all had colonization of the gastrostomy tube site. We were unable to eradicate MRSA from either the gastrostomy tube site or from the tracheal secretions of these three patients. One patient with a gastrostomy tube and tracheostomy (patient 17, Fig. 2) had colonization of the nares and the gastrostomy tube site. After two courses of therapy colonization had been eradicated, but this patient had recurrence of MRSA several months
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T a b l e 2 . MRSA antimicrobial resistance pattern
Antibiotic
Tested*
Trimethoprim-sulfamethoxazole Gentamicin Erythromycin Tetracycline Chloramphenicol Clindamycin Rifampin
29 29 29 29 28 29 12
Resistant n % 5 13 27 2 1 19 2
~17,2 44.8 93.1 6.9 3.6 64.5 16.6
*One isolatewas tested only for oxacillinsusceptibility.
after the study period concluded. Colonization was eliminated in two patients with gastrostomy tube site colonization (patients 19 and 25, Fig. 2). DISCUSSION
Some physicians question the need for expensive and disruptive infection control measures directed at limiting MRSA transmission, 16 whereas others advocate controls. Is'17'ls For three reasons, we believe that MRSA should be considered a serious nosocomial problem and some attempt should be made to control its spread. First, the widespread hospital-to-community outbreaks of penicillin-resistant S. aureus infection that occurred from 1946 to 196619 have not been forgotten. It is interesting to note that all patients whose cases met our definition for c o m m u n i t y acquired MRSA had been outpatients at the children's hospital, a rehabilitation center, or outpatient clinics witifin 6 months of MRSA identification. In these cases, MRSA m a y have been associated with outpatient facility contact rather than actually being community acquired. MRSA colonization is usually associated with inpatient hospitalization, and ordinarily is not expected among individuals with only brief outpatient visits. Such potential spread of MRSA into the community would significantly complicate the outpatient m a n a g e m e n t of infection, which usually consists of treatment with oral antimicrobials active against methicillin-susceptible S. aureus. Second, MRSA has become an important cause of nosocomial outbreaks in hospitals and extended care facilities. 5'9'1°'17'2° In hospitals, as many as 30% to 60% of patients colonized with MRSA later have infection. 17 Third, even though MRSA appears to be no m o r e pathogenic than methicillinsusceptible S. aureus,16 the r e c o m m e n d e d antimicrobial agent for treatment of serious MRSA
AJIC
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infections is intravenous vancomycin.17 Vancomycin is both more expensive and more toxic than are the drugs used to treat methicillin-susceptible S. a u r e u s . Resistance to vancomycin has been noted in other bacteria, 2~-24 and there is concern that such resistance m a y develop in MRSA. We elected to institute MRSA infection control measures at our hospital in August 1988 because this outbreak represented a n e w introduction of MRSA. This rationale was cited in a recent review 6 of this topic as one circumstance that may w a r r a n t special infection control measures. Boyce 6 reported that the rapid institution of infection control measures w h e n MRSA is first introduced into the hospital is supported by the fact that of 46 published outbreak reports, all 11 hospitals with fewer than 20 cases achieved definite or probable eradication of MRSA; this compares with a 71% success rate in hospitals with 20 to 39 cases and a success rate of only 10% in hospitals with 40 or more cases. In addition to increased surveillance and isolation, we also elected to eradicate colonization from patients with systemic antimicrobial therapy. The reported effectiveness of such therapy is variable. 25-32Our p r i m a r y reason for the use of such a regimen was to reduce the MRSA microbial b u r d e n on the host. We realized that complete eradication of MRSA might not be
possible, but we hoped that by decreasing the reservoir nosocomial transmission of MRSA and subsequent infections might be reduced. To our knowledge, only one study examines the success of elimination of MRSA colonization in the pediatric population, a3 In that study topical mupirocin and 0.3% hexachlorophane p o w d e r were used t o t r e a t 12 infants in a special care bal3y unit. Five of these infants were reported to have recurrence of colonization. Our apparent success in eliminating colonization parallels that of previous studies in adult patients, but our data must be interpreted in the absence of a control group and our lack of knowledge about the natural history of MRSA colonization. Rao and coworkers 3° used a combination of rifampin, bacitracin ointment, and chlorhexidine showers for 7 days in 16 patients. Cultures from 56% of these patients were negative for MRSA at 7 days after therapy. Roccaforte and associates 3] reported successful eradication with trimethoprim-sulfamethoxazole plus rifampin and bacitracin ointment applied to the nares in 40 of 47 patients; however, relapse occurred in nine patients. Mean duration of treatment was 6.0 _ 2.4 days. Winn and associates 34 were successful in eliminating colonization in 10 of 12 patients with nasal and extranasal MRSA with rifampin, trimethoprim-sulfamethoxazole,
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T a b l e 3. Suspected source, clinical site, antimicrobial resistance, and phage typing of MRSA in 19 patients whose isolates were available for phage typing Pt.
MRSA Source
Site
Antlmicrobial resistance
2 3 4 7 8 10 9 13 14 17 18 6 15 26 21 28 29 30 5
N N PLCF N CA N PLCF N PLCF PLCF PLCF PLCF PLCF PLCF CA CA PLCF PLCF PLCF
Throat Eye Foot Sputum Sputum Back tissue Wound Peritoneal Fluid Nasopharynx Gastrostomy tube Axilla Urine Nasopharynx Nasopharynx Wound Urine Nares Gastrostomy tube Gastrostomy tube
EES, GEN, IMIP, TMP-SX EES, GEN CHLORQ, CLD, EES, IMIP EES, GEN EES, GEN EES CLD EES, IMIP EES GEN CLD EES CLD EES, IMIP CLD EES CLD EES CLD EES, IMIP, RIF CLD EES, IMIP EES TETRA CLD, EES, GEN, TMP-SX No other testing EES, GEN, IMIP CLD, EES, RIF
Phage type (100 x RTD) NR NR 54/75/77/83A 75 75 6/54/75/77/83A/81 54/75/77/83A 75 54/75/77/83A 54/75/77/83A 54/75/77/83A 54/75/77/83A 54/75/77/83A 54/75/77/83A NR 80* 47/54/75/83A 75 47/54/75/83A
Isolatesfrom patients5, 28, 29, and 30 werephagetypedas a separatebatch. RTD,Routinetest dilution;N, nosocomial;EES,erythromycin;GEN,gentamlcin; IMIP, irnipenem; TMP-SX,trimethoprim-sulfamethoxazole;NR, not recorded; CHLORO, chloramphenicol; CLD, clindamycin; CA, community acquired; RIF, rifampin; TETRA,tetracycline. *Phage group I; all others reactedin phage group III.
and intranasal bacitracin for 5 days. Ellison and colleaguess2 used 5 days of rifampin plus trimethoprim-sulfamethoxazolein 14 patients and staff members. Eight of 12 persons had elimination of colonization with initial therapy; however, two patients later had recurrences. Extranasal colonization, especially in the presence of foreign bodies, has been associated with failure to eradicate MRSA. a~ Winn and associates 34 reported treatment failure in three patients with wound and nares colonization when rifampin was used with bacitracin for 5 days. In the study of Roccaforte and coworkers, aj 4 of 22 patients with extranasal colonization had treatment failure. In our patients, treatment failure was more common among patients with gastrostomy tubes and tracheostomies; however, two of three patients in this group were colonized with rifampin-resistant organisms. It is not clear what effects each of these factors had on failure to eliminate colonization. Resistance of MRSA at our institution to multiple antibiotics is consistent with the patterns described by others, a*-a6 Rifampin resistance has been observed during therapy, s4"aT"aa Bitar and co]leagues26 reported an outbreak of rifampinresistant MRSA among hospitalized adults. MRSA strains resistant to both rifampin and
trimethoprim-sulfamethoxazole have also been reported, sg"*° Emergence of rifampin and trimethoprim-sulfamethoxazole resistance in MRSA necessitates the testing of MRSA strains for susceptibility to these drugs when elimination of colonization is considered. Most reported outbreaks of MRSA have been associated with a predominant strain, although more than one strain may be present. 9'25'2s Bacteriophage typing has been a standard epidemiologic tool in the evaluation of S. a u r e u s outbreaks. However, recent studies have shown that phage typing of MRSA isolates is less reliable than plasmid analysis. 41,42 In this outbreak, a phage type common to the PLCF was identified in the eight PLCF patient isolates tested in the first batch. The three PLCF isolates in the second batch were different from those identified in the first batch (Table 3). Discordant phage type results seen in the PLCF isolates tested in the second group may have been related to lack of reproducibility or to instability of the isolates. We believe that phage typing can be a useful epidemiologic tool; however, we suggest that all MRSA isolates undergo testing in one batch. In the 2 years since the conclusion of this study, 2 1 new case~ of MRSA have been identified among our pediatric patients. Five of these cases met our
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definition as c o m m u n i t y - a c q u i r e d cases. One patient w a s t r a n s f e r r e d f r o m a n o t h e r a c u t e c a r e facility to the c h i l d r e n ' s hospital. E l e v e n n o s o c o mial cases h a v e o c c u r r e d in the c h i l d r e n ' s hospital. These h a v e b e e n c o n f i n e d to several timea s s o c i a t e d clusters in the n e o n a t a l intensive c a r e unit. B e c a u s e of u n k n o w n effects of r i f a m p i n a n d t r i m e t h o p r i m - s u l f a m e t h o x a z o l e in neonates, use of these a g e n t s in this p o p u l a t i o n has b e e n limited. P L C F patients c o l o n i z e d w i t h M R S A r e m a i n in isolation at the PLCF. Patients t r a n s f e r r e d f r o m the P L C F or o t h e r l o n g - t e r m c a r e facilities c o n tinue to be p l a c e d in isolation o n a d m i s s i o n to the c h i l d r e n ' s hospital, a n d s u r v e i l l a n c e culture s a m ples are obtained. I s o l a t i o n is c o n t i n u e d if M R S A is identified. P r e v i o u s l y identified M R S A cases are flagged in the hospital c o m p u t e r , a n d patients are isolated if r e a d m i t t e d . T h e r a p y to eliminate colon i z a t i o n is n o w d i r e c t e d t o w a r d patients w h o s e u n d e r l y i n g c o n d i t i o n r e q u i r e s l o n g - t e r m hospitalization o r t h o s e w h o a r e r e s i d e n t s of a l o n g - t e r m c a r e facility. W e believe that o u r infection c o n t r o l a n d c o l o n i z a t i o n e l i m i n a t i o n efforts have b e e n successful. N o s o c o m i a l cases h a v e b e e n limited to one unit, the n e o n a t a l intensive c a r e unit; the original s o u r c e for i n t r o d u c t i o n of M R S A to this unit has n o t b e e n identified. Despite multiple hospital a d m i s s i o n s of P L C F patients c o l o n i z e d with M R S A a n d a d m i s s i o n s of patients w i t h c o m m u n i t y - a c q u i r e d MRSA, n o s o c o m i a l t r a n s m i s s i o n has n o t b e e n a s s o c i a t e d with these patients. To o u r k n o w l e d g e , this is the first r e p o r t of M R S A a s s o c i a t e d w i t h a PLCF. The P L C F c o u l d n o t be c o n f i r m e d as the s o u r c e of i n t r o d u c t i o n of M R S A into the c h i l d r e n ' s hospital. P r o m p t institution of M R S A surveillance, b a r r i e r isolation, a n d t h e r a p y to e l i m i n a t e c o l o n i z a t i o n in p a t i e n t s s h o u l d be c o n s i d e r e d in hospitals with a n e w i n t r o d u c t i o n o f MRSA. We thank the staffs of both the pediatric long-term care facility and Kosair Children's Hospital for their cooperation in this effort to reduce MRSA transmission, and we thank Beverly Beckman for her secretarial assistance. References
1. Haley RW, Hightower AW, Khabbaz RF, et al. The emergence of methicillin-resistant Staphylococcus aureus infections in United States hospitals. Ann Intern Med 1983;97:297-308. 2. Boyce JM, Causey WA. Increasing occurrence of methicillin-resistant Staphylococcus aureus in the United States. Infect Control 1982;3:377-83. 3. Casewell MW. Epidemiology and control of the "modern"
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methicillin-resistant Staphylococcus aureus. J Hosp Infect 1986;7(Suppt A):I-I 1: 4. Jarvis WR, Thornsberry C, Boyce J, Hughes JM. Methicinin-resistant Staphylococcus aureus at children's hospitals in the United States. Pediatr Infect Dis 1985;4: 651-5. 5. Boyce JM. Increasing prevalence of methicinin-resistant Staphylococcus aureus in the United States. Infect Control Hosp Epidemiol 1990;11:639-42. 6. Boyce JM. Should we vigorously try to contain and control methicinin-resistant Staphylococcus aureus? Infect Control Hosp Epidemiol 1991;12:46-54. 7. Thompson RL, Caberzuda I, Wenzel PP. Epidemiology of nosocomial infections caused by mcthiciIlin-resistant Staphylococcus aureus. Ann Intern Med 1982;97:309-17. 8. O'Toole RD, Drew WL, Dahlgren BJ, et al. An outbreak of methicillin-resistant Staphylococcus aureus infection. Observations in hospital and nursing home. JAMA 1970;213: 257-63. 9. Storeh GA, Radcliff JL, Meyer PL, Hinrichs JH. Methicillin-resistant Staphylococcus aureus in a nursing home. Infect Control 1987;8:24-9. 10. Thomas JC, Bridges J, Water S, Vogt J, Kilman L, Hancock G. Transmission of and Control of methicillin-resistant Staphylococcus aureus in a skilled nursing facility. Infect Control Hosp Epidemiol 1989;10:106-10. 11. Lairscey R, Buck GE. Performance of four slide agglutination methods for identification of Staphylococcus aureus when testing methicillin-resistant staphylococci. J Clin Microbiol 1987;25:181-2. 12. McDougal LK, Thornsberry C. New recommendations for disk diffusion antimicrobial susceptibility tests for methicinin-resistant (heteroresistant) staphylococci. J Clin Microbiol 1984;19:482-8. 13. National Committee for Clinical Laboratory Standards. Performance standards for antimicrobic disc susceptibility tests. Villanova, Pennsylvania: National Committee for Clinical Laboratory Standards, 1979. 14. Garner JS, Jarvis WR, Emori TG, Horma TC, Hughes JM. CDC definitions for nosocomial infection. Infect Control 1988;16:138-40. 15. Garner JS, Simmons BP. Guideline for isolation precautions in hospitals. Infect Control 1983;4(4 Suppl):245-325. 16. McManus AT, Mason AD, Pruit BA. What's in a name? Is methicinin-resistant Staphylococcus aureus just another S. aureus when treated with vancomycin? Arch Surg 1989; 124:1456-9. 17. Boyce JM. Methicillin-resistant Staphylococcus aureus detection, epidemiology, and control measures. Infect Dis Clinics North Am 1989;3:901-914. 18. Standiford HC. Methicillin-resistant Staphylococcus aureus infections: it's time to get tough. Infect Control 1987;8:187-9. 19. Wise RI, Ossman EA, Littlefield DR. Personal reflections on nosocomial staphylococcal infections and the development of hospital surveillance. Rev Infect Dis 1989;11: 1005-19. 20. Kauffman CA, Bradley SF, Terpenning MS. Methicillinresistant Staphylococcus aureus in long-term care facilities. Infect Control Hosp Epidemiol 1990;11:600-3. 21. Sanyal D, Johnson AP, Georg RC, Cookson BD, Williams AJ. Peritonitis due to vancomycin-resistant Staphylococcus epidermidis [Letter]. Lancet 1991;337:54. 22. Veach LA, Pfaller MA, Barnett M, Koontz FP, Wenzel PP.
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Vancomycin resistance in Staphylococcus haemolyticus causing colonization and bloodstream infection. J Clin Microbiol 1990;28:2064-8. 23. Johnson AP, Uttley AH, Woodford N, George RC. Resistance to vancomycin and teicoplanin: an emerging clinical problem. Clin Microbiol Rev 1990;3:280-91. 24. Kaplan AH, Gilligan PH, Facklam RR. Recovery of resistant enterococci during vancomycin prophylaxis. J Clin Microbiol 1988;26:1216-8. 25. Ward Tr, Winn RE, Hartstain AL, et al. Observations relating to an interhospital outbreak of methicillinresistant Staphylococcus aureus: role, of antimicrobial therapy in infection control. Infect Control 1981;2:453-9. 26. Bitar CM, Mayhall CG, Lamb VA, et al. Outbreak due to methicillin- and rifampin-resistant Staphylococcus aureus: epidemiology and eradication of the resistant strain from the hospital. Infect Control 1987;8:15-23. 27. Dacre JE, Emmerson AM, Jenner EA. Nasal carriage of gentamicin and methicillin-resistant Staphylococcus aureus treated with topical pseudomonic acid [Letter]. Lancet 1983;2:1036. 28. Bacon AE, Jorgensen KA, Wilson KH, Kauffman CA. Emergence of nosocomial methicillin-resistant Staphylococcus aureus and therapy of colonized personnel during a hospital-wide outbreak. Infect Control 1987;8:145-50. 29. Denning DW, Haiduven-Griftith D. Eradication of lowlevel methicillin-resistantStaphylococcus aureus skin colonization with topical mupirocin. Infect Control Hosp Epidemiol 1988;9:261-3. 30. Rao N, Jacobs S, Joyce L. Cost-effective eradication of an outbreak of methicillin-resistantStaphylococcus aureus in a community teaching hospital. Infect Control Hosp Epidemiol 1988;9:255-60. 31. Roccaforte JS, Bittner MJ, Stumpf CA, Preheim LC. Attempts to eradicate methicillin-resistantStaphylococcus aureus colonization with the use of trimethoprimsulfamethoxazole, rifampin and bacitracin. AM J INFECT CONTROL 1988;16:141-5. 32. Ellison RT, Judson FN, Peterson LC, et al. Oral rifampin and trimethoprim/sulfa-methoxazole therapy in asymptomatic carriers of methicillin-resistant Staphylococcus aureus infections. West J Med 1984;140:735-40.
M R S A in a c h i l d r e n s " h o s p i t a l
255
33. Davies EA, Emmerson AM, Hogg GM, Patterson MF, Shield MD. An outbreak of infection with a methicillinresistant Staphylococcus aureus in a special care baby unit: value of topical mupirocin and of traditional methods of infection control. J Hosp Infect 1987;10:120-8. 34. Winn RE, Ward TF, Hartstein AI, et al. Epidemiological, bacteriological, and clinical observations on an interhospital outbreak of nafcillin-resistantStaphylococcus aureus. In: Nelson JD, Grassi D, eds. Current chemotherapy and infectious diseases, vol 2. Washington, DC: American Society for Microbiology, 1980:1096-7. 35. Richmond A, Simberkoff M, Schaefler S, et al. Resistance of Staphylococcus aureus to semisynthetic penicillins and cephalothin. J Infect Dis 1977;135:108-12. 36. Brumfitt W, Hamilton-Miller J. Methicillin-resistant Staphylococcus aureus. N Engl J Med 1989;320:118896. 37. Eng RH, Smith SM, Tillen M, Cherubin C. Rifampin resistance development during the therapy of methicillinresistant Staphylococcus aureus infection. Arch Intern Med 1985;145:146-8. 38. Simon GL, Smith RH, Sande MA. Emergence of rifampinresistant strains of Staphylococcus aureus during combination therapy with vancomycin and rifarnpin: a report of two cases. Rev Infect Dis 1983;5(Suppl 3):$507-8. 39. Coovadia YM, Bhana RH, Johnson AP, Haffejee I, Marples RR. A laboratory confirmed outbreak of rifampinmethicillin resistant Staphylococcus aureus MRSA in a newborn nursery. J Hosp Infect 1989;14:303-12. 40. Ruane DJ, Morgan MA, Citron DM, Mulligan ME. Failure of rapid agglutination methods to detect oxacillin-resistant Staphylococcus aureus. J Clin Microbiol 1986;24:490-2. 41. Rhinehart E, Shlaes DM, Keys TF, et al. Nosocomial clonal dissemination of methicillin-resistant Staphylococcus aureus: elucidation by plasmid analysis. Arch Intern Med 1987;147:521-4. 42. Archer GL, Mayhall CG. Comparison of epidemiological markers used in the investigation of an outbreak of methicillin-resistant Staphylococcus aureus infections. J Clin Microbiol 1983;18:395-9.
