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Bacterial contamination of cystic fibrosis clinics
Journal of Cystic Fibrosis 8 (2009) 186 – 192 www.elsevier.com/locate/jcf
Bacterial contamination of cystic fibrosis clinics☆ Jonathan B. Zuckerman a,⁎, Deborah E. Zuaro b , B. Stephen Prato c , Kathryn L. Ruoff b , Rafal W. Sawicki d , Hebe B. Quinton e , Lisa Saiman f , the Infection Control Study Group a
Department of Medicine, University of Vermont and Maine Medical Center, Portland, Maine, United States Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, United States c Department of Surgery, Maine Medical Center, Portland, Maine, United States d Grand View Hospital, Sellersville, Pennsylvania, United States Dartmouth Institute for Health Policy and Clinical Practice and Dartmouth Medical School, Lebanon, New Hampshire, United States f Department of Pediatrics, Columbia University, New York, New York, United States b
e
Received 14 October 2008; received in revised form 19 December 2008; accepted 16 January 2009 Available online 28 February 2009
Abstract Background: Respiratory pathogens from CF patients can contaminate inpatient settings, which may be associated with increased risk of patientto-patient transmission. Few data are available that assess the rate of bacterial contamination of outpatient settings. We determined the frequency of contamination of CF clinics and the effectiveness of alcohol-based disinfectants in reducing hand carriage of bacterial pathogens. Methods: We conducted a point prevalence survey and before–after trial in outpatient clinics at 7 CF centers. The study examined CF patients with positive respiratory cultures for Pseudomonas, Staphylococcus, Stenotrophomonas or Burkholderia species. Hand carriage and environmental contamination with respiratory pathogens were assessed during clinic visits (Part I) and the effectiveness of hand hygiene performed by CF patients (Part II) was determined using molecular typing of recovered isolates. Results: In Part I (n = 97), the contamination rate was 13.6%. Pseudomonas and S. aureus, including methicillin-resistant strains, were cultured from patients' hands (7%), the exam room air (8%), and less commonly, environmental surfaces (1%). In Part II (n = 100), the hand carriage rate of pathogens was 13.5% and 4 participants without initial detection of pathogens had hand contamination when recultured at the end of the clinic visit. Conclusions: Respiratory pathogens from CF patients can contaminate their hands and the clinic environment, but the actual risk of patient-topatient transmission in the outpatient setting remains difficult to quantify. These findings support several recommendations CF infection control recommendations including hand hygiene for staff and patients, contact precautions for certain pathogens, and disinfecting equipment and surfaces touched by patients and staff. © 2009 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved. Keywords: Cystic fibrosis; Infection control; Outpatient; Pseudomonas; Burkholderia; Staphylococcus
1. Introduction Abbreviations: BCC, Burkholderia cepacia complex; CF, cystic fibrosis; CFU, colony forming unit; FEV1, forced expiratory volume in one second; MRSA, methicillin resistant Staphylococcus aureus; MSSA, methicillin sensitive Staphylococcus aureus; PA, Pseudomonas aeruginosa; PFGE, pulsed field gel electrophoresis; SA, Staphylococcus aureus; SM, Stenotrophomonas maltophilia. ☆ Source of support: Grant No. ZUCKER03A0 from the Cystic Fibrosis Foundation. ⁎ Corresponding author. Division of Pulmonary and Critical Care, Maine Medical Center, 22 Bramhall St., Portland, Maine 04102, United States. Tel.: +1 207 662 2770; fax: +1 207 662 4691. E-mail address: [email protected] (J.B. Zuckerman).
Chronic infections of the respiratory tract are well-recognized complications of cystic fibrosis (CF). Though considerable resources are expended to manage exacerbations of pulmonary disease, over time, a progressive decline in pulmonary function occurs and ultimately is the leading cause of death. Patients with CF are infected with predictable pathogens including Pseudomonas aeruginosa (PA), Staphylococcus aureus (SA), and Burkholderia species. While the source of these pathogens is often unknown, there is ample
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J.B. Zuckerman et al. / Journal of Cystic Fibrosis 8 (2009) 186–192
evidence demonstrating patient-to-patient transmission of bacteria in non-healthcare settings in which extensive social contact occurs, such as summer camps or households [1–7] and on inpatient CF units [8–15]. Respiratory tract pathogens from CF patients can survive on inanimate surfaces and contaminate the inpatient hospital environment where patient residency is prolonged [16–20]. Direct and indirect evidence of patient-topatient spread of Burkholderia dolosa and Pseudomonas sp., respectively, within CF clinic populations has been reported [21,22]. However, fewer studies have directly assessed the risk of contamination of outpatient facilities [23]. The need for additional data for outpatient settings was highlighted in a consensus document on infection control for CF patients [24], which suggested that further study was warranted to develop evidence-based standards for best practices in CF clinics. This information gap formed the basis for the current investigation which sought to test two hypotheses: [1] during office visits, respiratory pathogens from CF patients contaminate the hands of patients and healthcare professionals as well as the air and environmental surfaces in examination rooms. [2] Alcoholbased hand hygiene disinfectants reduce the rate of patient hand carriage of respiratory pathogens. Some results of these results have been reported in abstract form [25–27]. 2. Methods
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2.3.2. Environmental cultures Prior to each CF clinic session in Part I, environmental cultures were collected in the study examination rooms using a premoistened swab. Sites included sinks, door handles, stethoscopes, and otoscopes. During the study visits, these sites were cultured within 10 min of the participant leaving the room and prior to cleaning the room. At the end of the clinic session, common areas including the bathroom, arm chairs in the waiting area and toys were cultured. 2.3.3. Air sampling Air sampling was performed with a single-stage impactor hooked in series to a vacuum pump (1-STG Viable Particle Sampler, Andersen Instruments Inc., Atlanta, GA) with a collection rate of 28.3 l of air per minute. Prior to clinic, the examination room air was sampled for 30 min onto a blood agar plate. During study visits, the impactor was placed 3 ft in front of the participant and the air was sampled throughout the visit. The participants moved about the room as was customary for each study site. The air sample was estimated to be 4.3–23.5% of the volume of each examination room. 2.3.4. Hand cultures In Part I, staff hands were cultured before clinic and after participant encounters, and participants' hands were cultured prior to performing hand hygiene as previously described [28].
2.1. Study design In Part I, we sought to determine how frequently the respiratory pathogens of CF patients would be recovered from their hands, the hands of CF team members, the air, or environmental surfaces within examination rooms where patients were evaluated during CF outpatient visits. In Part II, we assessed if hand hygiene performed by CF patients using alcohol-based rubs reduced their hand carriage of respiratory pathogens. 2.2. Study sites and study participants Seven CF Centers, caring for approximately 600 CF patients, received Institutional Review Board approval to participate in this study. Eligible participants were ≥ 6 years of age with a history of sputum production and previous cultures for SA, PA, Stenotrophomonas maltophilia (SM), and/or Burkholderia cepacia complex (BCC). Potential subjects were recruited during CF clinic visits, and all participants signed consent prior to enrollment. 2.3. Sampling techniques for CF respiratory pathogens 2.3.1. Respiratory tract cultures Pulmonary function testing was performed in the examination room and then either an expectorated sputum or oropharyngeal culture (if sputum was not produced) was obtained. The sites' study team sampled the specimen using a rayon-tipped swab (Remel, Lenexa, KS) which was sent in modified Stewart's medium to the core microbiology laboratory for study purposes.
2.3.5. Recovery experiments To assess the sensitivity of each of the culturing techniques used in the study, several recovery experiments were performed. Broth culture suspensions of 105 colony forming units (CFU) per ml of the organisms of interest (i.e., PA, SA, SM and BCC), were prepared using a colorimeter and serial dilutions were made (range 101–105 CFU/ml). In the first experiment, 0.5 ml of each dilution was inoculated onto a dry laboratory bench covering an area 10 cm by 10 cm. After 5 min, the area was sampled with a pre-moistened swab. In the second experiment, 0.5 ml of each dilution was nebulized for 5 min (0.84 cm3) from a Pari-LC nebulizer driven by a Pulmo-Aide compressor. The mouthpiece of the nebulizer was placed 12 in. from the inlet of the impactor and samples were collected onto a blood agar plate. The level of detection for each of these recovery experiments was approximately 102 CFU (data not shown). Recovery experiments were also performed for “glove juice” sampling. An inoculum of the designated organism in log phase growth was prepared in 50 ml of sampling buffer. The sample was refrigerated overnight to duplicate the transport conditions required for specimens sent to the core laboratory. The sampling buffer was then centrifuged and suspensions of the pellet were diluted and plated. The level of detection by this method was approximately 102 CFU for each study organism (data not shown). 2.3.6. Hand decontamination with alcohol-based disinfectant In Part II, the effectiveness of hand hygiene in reducing hand carriage of respiratory pathogens was studied. Participants from Part I were eligible for Part II, but were recruited at a different clinic visit. Participant hands were cultured at the start of the visit and then
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Table 1 Comparison of participant characteristics in Part I and Part II. Participant characteristics
Part I
Part II
N = 97
N = 100
Pediatric participant Study organism in respiratory culture
47 (48%) 83 (86%)
50 (50%) 74 (74%)
Study organism isolated⁎ PA SA BCC SM Pulmonary exacerbation
52% 40% 6% 11% 28 (29%)
38% 50% 2% 8% 14 (14%)
⁎Some participants had more than one pathogen isolated from their respiratory tract.
hand hygiene was performed with the alcohol-based product in use at each site, according to the manufacturers' instructions. At the completion of visits, participant hands were re-cultured. 2.4. Microbiology and molecular epidemiology Specimens were transported overnight on ice to the core laboratory and processed in accordance with CF Foundation guidelines [29]. Isolates of BCC were sent to the U.S. CF Foundation B. cepacia Research Laboratory and Repository for confirmation of identity [30]. If the same species was recovered from a participant's respiratory tract and from environmental, air, and/or hand cultures obtained during their study visit, then each potential match was analyzed by pulsed field gel electrophoresis (PFGE), as previously described using the following restriction enzymes for the target organisms: SA — SmaI; PA — SpeI; SM — XbaI; BCC — SpeI)[31]. Strains were considered “indistinguishable” if the band patterns were identical, “probably related” if there was a 1–2 band difference, “possibly related” if there was a 3–4 band difference, and “unrelated” if there was N 4 band difference [32]. If a strain(s) from a participant's respiratory tract was indistinguishable, probably or possibly related to any relevant strain(s) from environmental surfaces, hands, or air, this was interpreted as a match consistent with bacterial contamination of the CF clinic.
used to test the associations of clinical factors and bacterial contamination. The analyses were done using Stata Statistical Software, version 9.2, College Station, TX: Stata Corporation, 2006. A sample size of 100 subjects for Part I of the study provided 90% power to detect a contamination rate of 3% by any study organism. 3. Results In Part I, 97 participants were enrolled from 7 study sites (median 10 participants per site, range 6–36). In Part II, 100 participants were enrolled from 6 of these sites (median 15 participants per site, range 6–34). Participant characteristics including their respiratory pathogens are shown (Table 1). The median duration of study visits was 72 min (range 60–170 min). In Part I, 97 participants were enrolled during 55 clinic sessions and 1887 cultures were obtained. These included 605 pre-clinic cultures, 1030 visit cultures, and 252 post-clinic cultures. Potential respiratory pathogens were recovered from both the pre-clinic and post-clinic cultures (Table 2). The rate of positive pre-clinic cultures varied among the sites from 0% to 11% (mean 4.7%; 95% CI, 3.3%–6.8%). Surfaces of instruments such as pulse oximeters, stethoscopes and otoscopes were rarely contaminated; PA and SA were each recovered from a pre-clinic culture of a stethoscope. The rate of positive postclinic cultures among the sites ranged from 0% to 10.9% (mean 3.6%; 95% CI, 1.9–6.6%). Respiratory pathogens were detected on receptionists' counters, bathroom faucets, and waiting room chairs. Pre- and post-clinic cultures were not evaluated with PFGE for matching with participants' respiratory tract pathogens, as these were obtained in common areas frequented by study and non-study patients. In Part I, 81 participants had a pathogen of interest isolated from their respiratory tract which included 38 potential matches.
Table 2 Distribution of pathogens in Part I in pre-clinic, study visit, and post-clinic cultures. Culture sites
2.5. Assessment of potential risk factors associated with bacterial contamination To test the hypothesis that clinical factors might associate with an increased risk of bacterial contamination, the following were collected, as previously described, to assess for pulmonary exacerbations [33]: presence of fever or hemoptysis, and changes in the reported severity of cough, reported daily sputum volume, forced expiratory volume in one second (FEV1), weight, oxyhemoglobin saturation, and chest radiograph (if performed). Determination of protocol-defined pulmonary exacerbation was made by site investigators at the time of study encounters. 2.5.1. Statistical methods Exact confidence intervals were calculated using the binomial distribution. Chi-square or Fischer's exact tests were
Cultures PA a MSSA MRSA BCC SM obtained (#)
Pre-clinic cultures Staff hands 165 Examination room air 55 Environmental surfaces 330 Post-clinic cultures 252 Total pre- and post-clinic 802 cultures Study visit b Participant hands 97 Staff hands 291 Examination room air 97 Environmental surfaces 1067 Total study visit cultures 1552
8 3 2 5 18
5 2 2 7 16
1 0 0 0 1
0 1 0 0 1
0 0 0 0 0
3 0 4 0 7
1 0 3 0 4
2 0 1 1 4
0 0 0 0 0
0 0 0 0 0
a Abbreviations used in table: PA — P. aeruginosa, MSSA — methicillin susceptible S. aureus, MRSA — methicillin resistant S. aureus, BCC — B. cepacia complex, SM — S. maltophilia. b Study visit culture results show PFGE-confirmed matches.
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Eleven participants had protocol-defined PFGE matches, resulting in a contamination rate of 13.6% (95% CI, 6.8– 22.5%), as shown in Table 2 and Fig. 1. During 5 (6.2%) encounters, contamination of environmental surfaces or air was detected. The contamination rate varied among study sites from 0% (one site) to 33%, but site differences were not statistically significant due to sample size. With 3 participants more than one site was contaminated by a protocol-defined match. Methicillin-resistant SA (MRSA) was recovered from a participant's hands, air culture, and a pulse oximeter; both methicillin-susceptible SA (MSSA) and PA were recovered from the examination room air of another participant; and MSSA was recovered from a participant's hands and the air. During 10 study visits, air cultures grew bacteria (4 MSSA, 1 MRSA, and 5 PA) that did not match the participant's respiratory tract isolates. There were no significant differences in the contamination rates between adult versus pediatric participants (14.0% vs. 12.5%, respectively, p = 0.552) nor between participants with and without signs and symptoms of a pulmonary exacerbation (13.8% and 12.5%, respectively, p = 1.0). No contamination was observed from participants harboring BCC. In Part II, 74 participants had an organism of interest isolated from their respiratory tract and potential respiratory pathogens were recovered from some of their hands. Prior to alcohol-based hand hygiene, MSSA (n = 6), PA (n = 3), MRSA (n = 7) and SM (n = 1) were recovered and at the end of the study visit, MSSA (n = 7), PA (n = 4), MRSA (n = 7) and SM (n = 2) were recovered. PFGE results revealed that the respiratory pathogens of 13.5%
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(10/74) of participants were cultured from their hands prior to hand hygiene. At the end of the study visit, five of these participants had decontaminated their hands, but four additional patients had new detection of matched pathogens on their hands at the end of the visit (Fig. 2). In Part II there was a trend toward increased hand carriage in ill (28.6%, 95% CI 11.8–55%) vs. versus stable (11.6%, 95% CI 6.5–20.0%) patients (p = 0.10). 4. Discussion Providing effective infection control at CF centers is an important issue, as reports accrue about potential routes of transmission of respiratory pathogens within this susceptible patient population. However, the relative lack of data for the outpatient clinic setting has, in part, resulted in varying infection control policies at different CF Centers [34]. To our knowledge, this is the first systematic, multicenter study utilizing molecular typing to determine the rate of bacterial contamination of CF clinics with patient pathogens. The results of the current study are likely to be generalizable, as the study was conducted in a variety of practice settings including university-based clinics as well as office-based practices. Though study sites differed in the duration of clinic visits, team composition and number of patients seen per clinic, there was general conformity to certain practices: 1) patients were not required to wear masks 2) effort was made to minimize waiting room time for patients, and 3) spirometry was performed in the examination room, not in freestanding laboratory spaces.
Fig. 1. Representative PFGE gels from Part I of the study comparing respiratory and environmental isolates by PFGE. Panel A. Pseudomonas aeruginosa isolates from a single participant encounter with indistinguishable band pattern. Lane 1: sputum isolate Lane 2: air isolate Lane 3: participant hand isolate. Panel B. Staphylococcus aureus isolates from a single clinic showing unrelated band patterns. Lane 1: pre-clinic air isolate Lane 2: post-clinic bathroom faucet handle isolate Lane 3: pre-clinic staff hand isolate Lane 4: participant sputum isolate Lane 5: air isolate. Panel C. Pseudomonas aeruginosa isolates from a single patient encounter with possibly related band patterns. Lane 1: sputum isolate Lane 2: sputum isolate Lane 3: air isolate.
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Fig. 2. Flow diagram of contamination events in Part I and Part II. This figure shows the rates of isolation of the pathogens of interest from the respiratory tract of participants. For Part I the proportion of participants with available and unavailable isolates, the PFGE study-defined matches, and the source of isolates that matched participants' respiratory isolates are shown. For Part II, the proportion of participants with available and unavailable isolates and PFGE matches before hand hygiene and at the end of study visits are shown.
We found that bacterial contamination of participant hands (6 of 11 PFGE-defined matches in Part I and by study design, 14 of 14 matches in Part II) was most common. Unfortunately, hand hygiene performed at the start of clinic did not prevent subsequent contamination of the hands during study visits, as 4 participants had pathogens detected on their hands at the end of the visit that were not identified at the start. We do not believe this observation is due to ascertainment bias, as glove juice recovery experiments demonstrated a level of detection of 102 colony forming units (CFU). The finding is likely attributable to contamination of the hands during the visit and inability of alcohol rubs to prevent subsequent acquisition of viable organisms. This confirms that frequent hand hygiene should be performed throughout clinic visits. In the current era of multidrug-resistant bacteria, attention has focused on the role of the environment as a reservoir for potential pathogens, particularly in the healthcare setting [35,36]. Respiratory secretions from clinically stable CF patients contain a heavy burden of bacteria, typically 107– 108 CFU/g of sputum in adults and 104–105 CFU/g in young children [37,38]. Patient care equipment, including respiratory devices [39], can therefore harbor potential pathogens. As has been previously reported [40], we found that stethoscopes and pulse oximeters can become contaminated in the clinic, though infrequently. While specimens collected during the study visit could be definitively linked with a participant's respiratory tract, potential pathogens recovered from common sites in the clinic could not be matched with a specific subject due to the study design. Taken together, our results support consensus
guideline recommendations for disinfecting horizontal surfaces in healthcare settings serving CF patients [24,41], though CF centers face the challenge of maintaining adequate staff to clean exam rooms between patients [42]. We found that the contamination rates of participants with and without pulmonary exacerbation were similar. This finding corroborates published statements emphasizing that all CF patients may harbor transmissible pathogens and supports the practice of cough etiquette described in recent infection control consensus guidelines [24] and in revised guidelines for source containment of potential pathogens [43]. In this investigation, isolates from study participants were recovered from air in the exam rooms. Infectious droplets are known to be a mode of person-to-person spread of viral and bacterial pathogens [43] and have been linked to transmission in CF [24]. Other studies have detected organisms in the air of rooms in which CF patients received care as long as 45 min after they had left the room [44]. The infection control guidelines recommend that CF patients remain at least 3 ft apart to minimize droplet transmission, although recent data suggests that droplets may travel as far as 6–10 ft [43]. When respiratory droplets are aerosolized, transmission is more likely. The duration of time that droplets harboring viable bacteria may be suspended in the air varies and depends on both droplet characteristics and environmental characteristics such as humidity and temperature [43,45]. The infection control guidelines for CF currently consider the universal use of masks for CF patients to be an unresolved issue, as outbreaks in this population have been halted without the use of masks [46].
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Future studies should address the efficacy of mask use in CF and the potential infectivity of suspended droplets. Some limitations were identified in this study. Enrollment criteria stipulated that patients have a history of producing sputum harboring an organism of interest. However, not all patients were able to provide sputum samples during the study visit (Table 1), and not all respiratory specimens grew a study pathogen. Our molecular typing definition for a “match” could have misclassified strains exhibiting clonal variation. Finally, the study was not adequately powered to examine the effect of pulmonary exacerbation on hand contamination. The actual risk of patient-to-patient transmission of CF pathogens within the CF clinic remains difficult to quantify, as long-term observations of many patients utilizing costly methods such as those described in this study would be needed. In addition, patient acquisition of a new respiratory pathogen would not distinguish transmission from the clinic from transmission that occurred during contact elsewhere. Nevertheless, it would appear to be a worthy goal to minimize contamination of CF clinics in ways that are practical and effective without jeopardizing the demonstrated benefits of care provided by CF teams [47]. This study, performed at a variety of CF centers, demonstrated a measurable contamination rate of patients' hands and the clinic environment. We confirmed that the use of alcoholbased hand hygiene products effectively reduced hand carriage of respiratory pathogens, but also found that repeated hand hygiene during office visits is needed to control the risk of recurrent contamination. Acknowledgments The authors thank Drs. Joseph Schwartzman and Gerald O'Connor for input into the design of this study and review of the manuscript. We also thank Drs. Lynne Quittell and Jane Siegel for their helpful comments. We gratefully acknowledge the valuable contributions of Otelah Perry, Torrie Pandora, and Lorrie Hillsgrove from the Dartmouth-Hitchcock Microbiology Laboratory for performance of isolate identification, pulsed field gel electrophoresis and recovery controls. Appendix A. Participating site investigators (alphabetical order) Anne Marie Cairns, Maine Medical Center, Portland, ME; Stanley Fiel, Atlantic Health System, Morristown, NJ; Thomas Lahiri, Fletcher-Allen Medical Center, Burlington, VT; Thomas Lever, Eastern Maine Medical Center, Bangor, ME; H. Worth Parker, Dartmouth-Hitchcock Medical Center, Hanover, NH; Samiya Razvi, Columbia University, New York, NY; Dennis Stokes, Dartmouth-Hitchock Medical Center, Lebanon, NH; Laurie Varlotta, St. Christopher’s Hospital for Children, Philadelphia, PA; Laurie Whittaker, Fletcher-Allen Medical Center Burlington, VT. Research coordinators (alphabetical order) Deborah Conklin, St. Christopher’s Hospital for Children, Philadelphia, PA; Angela Ferro, Fletcher-Allen Medical Center,
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Burlington, VT; David Kissin, Maine Medical Center, Portland, ME; Paula Lomas, Morristown Memorial Hospital, Morristown, NJ; Bonnie Peterson, Dartmouth-Hitchcock Medical Center, Hanover, NH; Amy Savage, Fletcher-Allen Medical Center, Burlington, VT; Becky Welch, Eastern Maine Medical Center, Bangor, ME; Julia Zhou, Columbia University, New York, NY. References [1] Adams C, Morris-Quinn M, McConnell F, West J, Lucey B, Shortt C, et al. Epidemiology and clinical impact of Pseudomonas aeruginosa infection in cystic fibrosis using AP-PCR fingerprinting. J Infect 1998;37:151–8. [2] Ojeniyi B, Frederiksen B, Hoiby N. Pseudomonas aeruginosa crossinfection among patients with cystic fibrosis during a winter camp. Pediatr Pulmonol 2000;29:177–81. [3] Schlichting C, Branger C, Fournier JM, Witte W, Boutonnier A, Wolz C, et al. Typing of Staphylococcus aureus by pulsed-field gel electrophoresis, zymotyping, capsular typing, and phage typing: resolution of clonal relationships. J Clin Microbiol 1993;31:227–32. [4] Goerke C, Kraning K, Stern M, Doring G, Botzenhart K, Wolz C. Molecular epidemiology of community-acquired Staphylococcus aureus in families with and without cystic fibrosis patients. J Infect Dis 2000;181:984–9. [5] Govan JR, Brown PH, Maddison J, Doherty CJ, Nelson JW, Dodd M, et al. Evidence for transmission of Pseudomonas cepacia by social contact in cystic fibrosis. Lancet 1993;342:15–9. [6] LiPuma JJ, Dasen SE, Nielson DW, Stern RC, Stull TL. Person-to-person transmission of Pseudomonas cepacia between patients with cystic fibrosis. Lancet 1990;336:1094–6. [7] Pegues DA, Carson LA, Tablan OC, FitzSimmons SC, Roman SB, Miller JM, et al. Acquisition of Pseudomonas cepacia at summer camps for patients with cystic fibrosis. Summer Camp Study Group. J Pediatr 1994;124:694–702. [8] McCallum SJ, Corkill J, Gallagher M, Ledson MJ, Hart CA, Walshaw MJ. Superinfection with a transmissible strain of Pseudomonas aeruginosa in adults with cystic fibrosis chronically colonised by P. aeruginosa. Lancet 2001;358:558–60. [9] Armstrong DS, Nixon GM, Carzino R, Bigham A, Carlin JB, Robins-Browne RM, et al. Detection of a widespread clone of Pseudomonas aeruginosa in a pediatric cystic fibrosis clinic. Am J Respir Crit Care Med 2002;166:983–7. [10] Givney R, Vickery A, Holliday A, Pegler M, Benn R. Methicillin-resistant Staphylococcus aureus in a cystic fibrosis unit. J Hosp Infect 1997;35:27–36. [11] Nadesalingam K, Conway SP, Denton M. Risk factors for acquisition of methicillin-resistant Staphylococcus aureus (MRSA) by patients with cystic fibrosis. J Cyst Fibros 2005;4:49–52. [12] Pegues DA, Schidlow DV, Tablan OC, Carson LA, Clark NC, Jarvis WR. Possible nosocomial transmission of Pseudomonas cepacia in patients with cystic fibrosis. Arch Pediatr Adolesc Med 1994;148:805–12. [13] Holmes A, Nolan R, Taylor R, Finley R, Riley M, Jiang RZ, et al. An epidemic of Burkholderia cepacia transmitted between patients with and without cystic fibrosis. J Infect Dis 1999;179:1197–205. [14] Clode FE, Metherell LA, Pitt TL. Nosocomial acquisition of Burkholderia gladioli in patients with cystic fibrosis. Am J Respir Crit Care Med 1999;160:374–5. [15] Kalish LA, Waltz DA, Dovey M, Potter-Bynoe G, McAdam AJ, Lipuma JJ, et al. Impact of Burkholderia dolosa on lung function and survival in cystic fibrosis. Am J Respir Crit Care Med 2006;173:421–5 Electronic publication 2005 Nov 4. [16] Doring G, Jansen S, Noll H, Grupp H, Frank F, Botzenhart K, et al. Distribution and transmission of Pseudomonas aeruginosa and Burkholderia cepacia in a hospital ward. Pediatr Pulmonol 1996;21:90–100. [17] Bosshammer J, Fiedler B, Gudowius P, von der Hardt H, Romling U, Tummler B. Comparative hygienic surveillance of contamination with
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[33] Fuchs HJ, Borowitz DS, Christiansen DH, Morris EM, Nash ML, Ramsey BW, et al. Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis. The Pulmozyme Study Group. N Engl J Med 1994;331:637–42. [34] Zhou J, Garber E, Saiman L. Survey of infection control policies for patients with cystic fibrosis in the United States. Am J Infect Control 2008;36:220–2. [35] Boyce JM, Havill NL, Otter JA, Adams NM. Widespread environmental contamination associated with patients with diarrhea and methicillinresistant Staphylococcus aureus colonization of the gastrointestinal tract. Infect Control Hosp Epidemiol 2007;28:1142–7 Electronic publication 2007 Aug 3. [36] Johnston CP, Cooper L, Ruby W, Carroll KC. Cosgrove SE, Perl TM. Epidemiology of community-acquired methicillin-resistant Staphylococcus aureus skin infections among healthcare workers in an outpatient clinic. Infect Control Hosp Epidemiol 2006;27:1133–6 Electronic publication 2006 Aug 31. [37] Ramsey BW, Pepe MS, Quan JM, Otto KL, Montgomery AB, WilliamsWarren J, et al. Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. Cystic Fibrosis Inhaled Tobramycin Study Group. N Engl J Med 1999;340:23–30. [38] Gibson RL, Emerson J, McNamara S, Burns JL, Rosenfeld M, Yunker A, et al. Significant microbiological effect of inhaled tobramycin in young children with cystic fibrosis. Am J Respir Crit Care Med 2003;167:841–9 Electronic publication 2002 Dec 12. [39] Burdge DR, Nakielna EM, Noble MA. Case-control and vector studies of nosocomial acquisition of Pseudomonas cepacia in adult patients with cystic fibrosis. Infect Control Hosp Epidemiol 1993;14:127–30. [40] Kerr JR, Martin H, Chadwick MV, Edwards A, Hodson ME, Geddes DM. Evidence against transmission of Pseudomonas aeruginosa by hands and stethoscopes in a cystic fibrosis unit. J Hosp Infect 2002;50:324–6. [41] Sehulster L, Chinn RY. Guidelines for environmental infection control in health-care facilities. Recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee (HICPAC). MMWR Recomm Rep 2003;52:1–42. [42] Garber EO, Zhou J, Alba L, Desai M, Angst D, Cabana MD, et al. Barriers to adherence to guidelines for infection control in CF. Pediatr Pulmonol 2005;Suppl 28:A391. [43] Siegel JD, Rhinehart E, Jackson M, Chiarello L, Committee HICPA. Guideline for isolation precautions: Preventing transmission of infectious agents in healthcare settings 2007; 2007. [44] Ensor E, Humphreys H, Peckham D, Webster C, Knox AJ. Is Burkholderia (Pseudomonas) cepacia disseminated from cystic fibrosis patients during physiotherapy? J Hosp Infect 1996;32:9–15. [45] Xie X, Li Y, Zhang T, Fang HH. Bacterial survival in evaporating deposited droplets on a teflon-coated surface. Appl Microbiol Biotechnol 2006;73:703–12 Electronic publication 2006 Oct 20. [46] Saiman L, Siegel J. Infection control in cystic fibrosis. Clin Microbiol Rev 2004;17:57–71. [47] Mahadeva R, Webb K, Westerbeek RC, Carroll NR, Dodd ME, Bilton D, et al. Clinical outcome in relation to care in centres specialising in cystic fibrosis: cross sectional study. BMJ 1998;316:1771–5.
Bacterial contamination of cystic fibrosis clinics☆ Jonathan B. Zuckerman a,⁎, Deborah E. Zuaro b , B. Stephen Prato c , Kathryn L. Ruoff b , Rafal W. Sawicki d , Hebe B. Quinton e , Lisa Saiman f , the Infection Control Study Group a
Department of Medicine, University of Vermont and Maine Medical Center, Portland, Maine, United States Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, United States c Department of Surgery, Maine Medical Center, Portland, Maine, United States d Grand View Hospital, Sellersville, Pennsylvania, United States Dartmouth Institute for Health Policy and Clinical Practice and Dartmouth Medical School, Lebanon, New Hampshire, United States f Department of Pediatrics, Columbia University, New York, New York, United States b
e
Received 14 October 2008; received in revised form 19 December 2008; accepted 16 January 2009 Available online 28 February 2009
Abstract Background: Respiratory pathogens from CF patients can contaminate inpatient settings, which may be associated with increased risk of patientto-patient transmission. Few data are available that assess the rate of bacterial contamination of outpatient settings. We determined the frequency of contamination of CF clinics and the effectiveness of alcohol-based disinfectants in reducing hand carriage of bacterial pathogens. Methods: We conducted a point prevalence survey and before–after trial in outpatient clinics at 7 CF centers. The study examined CF patients with positive respiratory cultures for Pseudomonas, Staphylococcus, Stenotrophomonas or Burkholderia species. Hand carriage and environmental contamination with respiratory pathogens were assessed during clinic visits (Part I) and the effectiveness of hand hygiene performed by CF patients (Part II) was determined using molecular typing of recovered isolates. Results: In Part I (n = 97), the contamination rate was 13.6%. Pseudomonas and S. aureus, including methicillin-resistant strains, were cultured from patients' hands (7%), the exam room air (8%), and less commonly, environmental surfaces (1%). In Part II (n = 100), the hand carriage rate of pathogens was 13.5% and 4 participants without initial detection of pathogens had hand contamination when recultured at the end of the clinic visit. Conclusions: Respiratory pathogens from CF patients can contaminate their hands and the clinic environment, but the actual risk of patient-topatient transmission in the outpatient setting remains difficult to quantify. These findings support several recommendations CF infection control recommendations including hand hygiene for staff and patients, contact precautions for certain pathogens, and disinfecting equipment and surfaces touched by patients and staff. © 2009 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved. Keywords: Cystic fibrosis; Infection control; Outpatient; Pseudomonas; Burkholderia; Staphylococcus
1. Introduction Abbreviations: BCC, Burkholderia cepacia complex; CF, cystic fibrosis; CFU, colony forming unit; FEV1, forced expiratory volume in one second; MRSA, methicillin resistant Staphylococcus aureus; MSSA, methicillin sensitive Staphylococcus aureus; PA, Pseudomonas aeruginosa; PFGE, pulsed field gel electrophoresis; SA, Staphylococcus aureus; SM, Stenotrophomonas maltophilia. ☆ Source of support: Grant No. ZUCKER03A0 from the Cystic Fibrosis Foundation. ⁎ Corresponding author. Division of Pulmonary and Critical Care, Maine Medical Center, 22 Bramhall St., Portland, Maine 04102, United States. Tel.: +1 207 662 2770; fax: +1 207 662 4691. E-mail address: [email protected] (J.B. Zuckerman).
Chronic infections of the respiratory tract are well-recognized complications of cystic fibrosis (CF). Though considerable resources are expended to manage exacerbations of pulmonary disease, over time, a progressive decline in pulmonary function occurs and ultimately is the leading cause of death. Patients with CF are infected with predictable pathogens including Pseudomonas aeruginosa (PA), Staphylococcus aureus (SA), and Burkholderia species. While the source of these pathogens is often unknown, there is ample
1569-1993/$ - see front matter © 2009 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.jcf.2009.01.003
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evidence demonstrating patient-to-patient transmission of bacteria in non-healthcare settings in which extensive social contact occurs, such as summer camps or households [1–7] and on inpatient CF units [8–15]. Respiratory tract pathogens from CF patients can survive on inanimate surfaces and contaminate the inpatient hospital environment where patient residency is prolonged [16–20]. Direct and indirect evidence of patient-topatient spread of Burkholderia dolosa and Pseudomonas sp., respectively, within CF clinic populations has been reported [21,22]. However, fewer studies have directly assessed the risk of contamination of outpatient facilities [23]. The need for additional data for outpatient settings was highlighted in a consensus document on infection control for CF patients [24], which suggested that further study was warranted to develop evidence-based standards for best practices in CF clinics. This information gap formed the basis for the current investigation which sought to test two hypotheses: [1] during office visits, respiratory pathogens from CF patients contaminate the hands of patients and healthcare professionals as well as the air and environmental surfaces in examination rooms. [2] Alcoholbased hand hygiene disinfectants reduce the rate of patient hand carriage of respiratory pathogens. Some results of these results have been reported in abstract form [25–27]. 2. Methods
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2.3.2. Environmental cultures Prior to each CF clinic session in Part I, environmental cultures were collected in the study examination rooms using a premoistened swab. Sites included sinks, door handles, stethoscopes, and otoscopes. During the study visits, these sites were cultured within 10 min of the participant leaving the room and prior to cleaning the room. At the end of the clinic session, common areas including the bathroom, arm chairs in the waiting area and toys were cultured. 2.3.3. Air sampling Air sampling was performed with a single-stage impactor hooked in series to a vacuum pump (1-STG Viable Particle Sampler, Andersen Instruments Inc., Atlanta, GA) with a collection rate of 28.3 l of air per minute. Prior to clinic, the examination room air was sampled for 30 min onto a blood agar plate. During study visits, the impactor was placed 3 ft in front of the participant and the air was sampled throughout the visit. The participants moved about the room as was customary for each study site. The air sample was estimated to be 4.3–23.5% of the volume of each examination room. 2.3.4. Hand cultures In Part I, staff hands were cultured before clinic and after participant encounters, and participants' hands were cultured prior to performing hand hygiene as previously described [28].
2.1. Study design In Part I, we sought to determine how frequently the respiratory pathogens of CF patients would be recovered from their hands, the hands of CF team members, the air, or environmental surfaces within examination rooms where patients were evaluated during CF outpatient visits. In Part II, we assessed if hand hygiene performed by CF patients using alcohol-based rubs reduced their hand carriage of respiratory pathogens. 2.2. Study sites and study participants Seven CF Centers, caring for approximately 600 CF patients, received Institutional Review Board approval to participate in this study. Eligible participants were ≥ 6 years of age with a history of sputum production and previous cultures for SA, PA, Stenotrophomonas maltophilia (SM), and/or Burkholderia cepacia complex (BCC). Potential subjects were recruited during CF clinic visits, and all participants signed consent prior to enrollment. 2.3. Sampling techniques for CF respiratory pathogens 2.3.1. Respiratory tract cultures Pulmonary function testing was performed in the examination room and then either an expectorated sputum or oropharyngeal culture (if sputum was not produced) was obtained. The sites' study team sampled the specimen using a rayon-tipped swab (Remel, Lenexa, KS) which was sent in modified Stewart's medium to the core microbiology laboratory for study purposes.
2.3.5. Recovery experiments To assess the sensitivity of each of the culturing techniques used in the study, several recovery experiments were performed. Broth culture suspensions of 105 colony forming units (CFU) per ml of the organisms of interest (i.e., PA, SA, SM and BCC), were prepared using a colorimeter and serial dilutions were made (range 101–105 CFU/ml). In the first experiment, 0.5 ml of each dilution was inoculated onto a dry laboratory bench covering an area 10 cm by 10 cm. After 5 min, the area was sampled with a pre-moistened swab. In the second experiment, 0.5 ml of each dilution was nebulized for 5 min (0.84 cm3) from a Pari-LC nebulizer driven by a Pulmo-Aide compressor. The mouthpiece of the nebulizer was placed 12 in. from the inlet of the impactor and samples were collected onto a blood agar plate. The level of detection for each of these recovery experiments was approximately 102 CFU (data not shown). Recovery experiments were also performed for “glove juice” sampling. An inoculum of the designated organism in log phase growth was prepared in 50 ml of sampling buffer. The sample was refrigerated overnight to duplicate the transport conditions required for specimens sent to the core laboratory. The sampling buffer was then centrifuged and suspensions of the pellet were diluted and plated. The level of detection by this method was approximately 102 CFU for each study organism (data not shown). 2.3.6. Hand decontamination with alcohol-based disinfectant In Part II, the effectiveness of hand hygiene in reducing hand carriage of respiratory pathogens was studied. Participants from Part I were eligible for Part II, but were recruited at a different clinic visit. Participant hands were cultured at the start of the visit and then
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Table 1 Comparison of participant characteristics in Part I and Part II. Participant characteristics
Part I
Part II
N = 97
N = 100
Pediatric participant Study organism in respiratory culture
47 (48%) 83 (86%)
50 (50%) 74 (74%)
Study organism isolated⁎ PA SA BCC SM Pulmonary exacerbation
52% 40% 6% 11% 28 (29%)
38% 50% 2% 8% 14 (14%)
⁎Some participants had more than one pathogen isolated from their respiratory tract.
hand hygiene was performed with the alcohol-based product in use at each site, according to the manufacturers' instructions. At the completion of visits, participant hands were re-cultured. 2.4. Microbiology and molecular epidemiology Specimens were transported overnight on ice to the core laboratory and processed in accordance with CF Foundation guidelines [29]. Isolates of BCC were sent to the U.S. CF Foundation B. cepacia Research Laboratory and Repository for confirmation of identity [30]. If the same species was recovered from a participant's respiratory tract and from environmental, air, and/or hand cultures obtained during their study visit, then each potential match was analyzed by pulsed field gel electrophoresis (PFGE), as previously described using the following restriction enzymes for the target organisms: SA — SmaI; PA — SpeI; SM — XbaI; BCC — SpeI)[31]. Strains were considered “indistinguishable” if the band patterns were identical, “probably related” if there was a 1–2 band difference, “possibly related” if there was a 3–4 band difference, and “unrelated” if there was N 4 band difference [32]. If a strain(s) from a participant's respiratory tract was indistinguishable, probably or possibly related to any relevant strain(s) from environmental surfaces, hands, or air, this was interpreted as a match consistent with bacterial contamination of the CF clinic.
used to test the associations of clinical factors and bacterial contamination. The analyses were done using Stata Statistical Software, version 9.2, College Station, TX: Stata Corporation, 2006. A sample size of 100 subjects for Part I of the study provided 90% power to detect a contamination rate of 3% by any study organism. 3. Results In Part I, 97 participants were enrolled from 7 study sites (median 10 participants per site, range 6–36). In Part II, 100 participants were enrolled from 6 of these sites (median 15 participants per site, range 6–34). Participant characteristics including their respiratory pathogens are shown (Table 1). The median duration of study visits was 72 min (range 60–170 min). In Part I, 97 participants were enrolled during 55 clinic sessions and 1887 cultures were obtained. These included 605 pre-clinic cultures, 1030 visit cultures, and 252 post-clinic cultures. Potential respiratory pathogens were recovered from both the pre-clinic and post-clinic cultures (Table 2). The rate of positive pre-clinic cultures varied among the sites from 0% to 11% (mean 4.7%; 95% CI, 3.3%–6.8%). Surfaces of instruments such as pulse oximeters, stethoscopes and otoscopes were rarely contaminated; PA and SA were each recovered from a pre-clinic culture of a stethoscope. The rate of positive postclinic cultures among the sites ranged from 0% to 10.9% (mean 3.6%; 95% CI, 1.9–6.6%). Respiratory pathogens were detected on receptionists' counters, bathroom faucets, and waiting room chairs. Pre- and post-clinic cultures were not evaluated with PFGE for matching with participants' respiratory tract pathogens, as these were obtained in common areas frequented by study and non-study patients. In Part I, 81 participants had a pathogen of interest isolated from their respiratory tract which included 38 potential matches.
Table 2 Distribution of pathogens in Part I in pre-clinic, study visit, and post-clinic cultures. Culture sites
2.5. Assessment of potential risk factors associated with bacterial contamination To test the hypothesis that clinical factors might associate with an increased risk of bacterial contamination, the following were collected, as previously described, to assess for pulmonary exacerbations [33]: presence of fever or hemoptysis, and changes in the reported severity of cough, reported daily sputum volume, forced expiratory volume in one second (FEV1), weight, oxyhemoglobin saturation, and chest radiograph (if performed). Determination of protocol-defined pulmonary exacerbation was made by site investigators at the time of study encounters. 2.5.1. Statistical methods Exact confidence intervals were calculated using the binomial distribution. Chi-square or Fischer's exact tests were
Cultures PA a MSSA MRSA BCC SM obtained (#)
Pre-clinic cultures Staff hands 165 Examination room air 55 Environmental surfaces 330 Post-clinic cultures 252 Total pre- and post-clinic 802 cultures Study visit b Participant hands 97 Staff hands 291 Examination room air 97 Environmental surfaces 1067 Total study visit cultures 1552
8 3 2 5 18
5 2 2 7 16
1 0 0 0 1
0 1 0 0 1
0 0 0 0 0
3 0 4 0 7
1 0 3 0 4
2 0 1 1 4
0 0 0 0 0
0 0 0 0 0
a Abbreviations used in table: PA — P. aeruginosa, MSSA — methicillin susceptible S. aureus, MRSA — methicillin resistant S. aureus, BCC — B. cepacia complex, SM — S. maltophilia. b Study visit culture results show PFGE-confirmed matches.
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Eleven participants had protocol-defined PFGE matches, resulting in a contamination rate of 13.6% (95% CI, 6.8– 22.5%), as shown in Table 2 and Fig. 1. During 5 (6.2%) encounters, contamination of environmental surfaces or air was detected. The contamination rate varied among study sites from 0% (one site) to 33%, but site differences were not statistically significant due to sample size. With 3 participants more than one site was contaminated by a protocol-defined match. Methicillin-resistant SA (MRSA) was recovered from a participant's hands, air culture, and a pulse oximeter; both methicillin-susceptible SA (MSSA) and PA were recovered from the examination room air of another participant; and MSSA was recovered from a participant's hands and the air. During 10 study visits, air cultures grew bacteria (4 MSSA, 1 MRSA, and 5 PA) that did not match the participant's respiratory tract isolates. There were no significant differences in the contamination rates between adult versus pediatric participants (14.0% vs. 12.5%, respectively, p = 0.552) nor between participants with and without signs and symptoms of a pulmonary exacerbation (13.8% and 12.5%, respectively, p = 1.0). No contamination was observed from participants harboring BCC. In Part II, 74 participants had an organism of interest isolated from their respiratory tract and potential respiratory pathogens were recovered from some of their hands. Prior to alcohol-based hand hygiene, MSSA (n = 6), PA (n = 3), MRSA (n = 7) and SM (n = 1) were recovered and at the end of the study visit, MSSA (n = 7), PA (n = 4), MRSA (n = 7) and SM (n = 2) were recovered. PFGE results revealed that the respiratory pathogens of 13.5%
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(10/74) of participants were cultured from their hands prior to hand hygiene. At the end of the study visit, five of these participants had decontaminated their hands, but four additional patients had new detection of matched pathogens on their hands at the end of the visit (Fig. 2). In Part II there was a trend toward increased hand carriage in ill (28.6%, 95% CI 11.8–55%) vs. versus stable (11.6%, 95% CI 6.5–20.0%) patients (p = 0.10). 4. Discussion Providing effective infection control at CF centers is an important issue, as reports accrue about potential routes of transmission of respiratory pathogens within this susceptible patient population. However, the relative lack of data for the outpatient clinic setting has, in part, resulted in varying infection control policies at different CF Centers [34]. To our knowledge, this is the first systematic, multicenter study utilizing molecular typing to determine the rate of bacterial contamination of CF clinics with patient pathogens. The results of the current study are likely to be generalizable, as the study was conducted in a variety of practice settings including university-based clinics as well as office-based practices. Though study sites differed in the duration of clinic visits, team composition and number of patients seen per clinic, there was general conformity to certain practices: 1) patients were not required to wear masks 2) effort was made to minimize waiting room time for patients, and 3) spirometry was performed in the examination room, not in freestanding laboratory spaces.
Fig. 1. Representative PFGE gels from Part I of the study comparing respiratory and environmental isolates by PFGE. Panel A. Pseudomonas aeruginosa isolates from a single participant encounter with indistinguishable band pattern. Lane 1: sputum isolate Lane 2: air isolate Lane 3: participant hand isolate. Panel B. Staphylococcus aureus isolates from a single clinic showing unrelated band patterns. Lane 1: pre-clinic air isolate Lane 2: post-clinic bathroom faucet handle isolate Lane 3: pre-clinic staff hand isolate Lane 4: participant sputum isolate Lane 5: air isolate. Panel C. Pseudomonas aeruginosa isolates from a single patient encounter with possibly related band patterns. Lane 1: sputum isolate Lane 2: sputum isolate Lane 3: air isolate.
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Fig. 2. Flow diagram of contamination events in Part I and Part II. This figure shows the rates of isolation of the pathogens of interest from the respiratory tract of participants. For Part I the proportion of participants with available and unavailable isolates, the PFGE study-defined matches, and the source of isolates that matched participants' respiratory isolates are shown. For Part II, the proportion of participants with available and unavailable isolates and PFGE matches before hand hygiene and at the end of study visits are shown.
We found that bacterial contamination of participant hands (6 of 11 PFGE-defined matches in Part I and by study design, 14 of 14 matches in Part II) was most common. Unfortunately, hand hygiene performed at the start of clinic did not prevent subsequent contamination of the hands during study visits, as 4 participants had pathogens detected on their hands at the end of the visit that were not identified at the start. We do not believe this observation is due to ascertainment bias, as glove juice recovery experiments demonstrated a level of detection of 102 colony forming units (CFU). The finding is likely attributable to contamination of the hands during the visit and inability of alcohol rubs to prevent subsequent acquisition of viable organisms. This confirms that frequent hand hygiene should be performed throughout clinic visits. In the current era of multidrug-resistant bacteria, attention has focused on the role of the environment as a reservoir for potential pathogens, particularly in the healthcare setting [35,36]. Respiratory secretions from clinically stable CF patients contain a heavy burden of bacteria, typically 107– 108 CFU/g of sputum in adults and 104–105 CFU/g in young children [37,38]. Patient care equipment, including respiratory devices [39], can therefore harbor potential pathogens. As has been previously reported [40], we found that stethoscopes and pulse oximeters can become contaminated in the clinic, though infrequently. While specimens collected during the study visit could be definitively linked with a participant's respiratory tract, potential pathogens recovered from common sites in the clinic could not be matched with a specific subject due to the study design. Taken together, our results support consensus
guideline recommendations for disinfecting horizontal surfaces in healthcare settings serving CF patients [24,41], though CF centers face the challenge of maintaining adequate staff to clean exam rooms between patients [42]. We found that the contamination rates of participants with and without pulmonary exacerbation were similar. This finding corroborates published statements emphasizing that all CF patients may harbor transmissible pathogens and supports the practice of cough etiquette described in recent infection control consensus guidelines [24] and in revised guidelines for source containment of potential pathogens [43]. In this investigation, isolates from study participants were recovered from air in the exam rooms. Infectious droplets are known to be a mode of person-to-person spread of viral and bacterial pathogens [43] and have been linked to transmission in CF [24]. Other studies have detected organisms in the air of rooms in which CF patients received care as long as 45 min after they had left the room [44]. The infection control guidelines recommend that CF patients remain at least 3 ft apart to minimize droplet transmission, although recent data suggests that droplets may travel as far as 6–10 ft [43]. When respiratory droplets are aerosolized, transmission is more likely. The duration of time that droplets harboring viable bacteria may be suspended in the air varies and depends on both droplet characteristics and environmental characteristics such as humidity and temperature [43,45]. The infection control guidelines for CF currently consider the universal use of masks for CF patients to be an unresolved issue, as outbreaks in this population have been halted without the use of masks [46].
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Future studies should address the efficacy of mask use in CF and the potential infectivity of suspended droplets. Some limitations were identified in this study. Enrollment criteria stipulated that patients have a history of producing sputum harboring an organism of interest. However, not all patients were able to provide sputum samples during the study visit (Table 1), and not all respiratory specimens grew a study pathogen. Our molecular typing definition for a “match” could have misclassified strains exhibiting clonal variation. Finally, the study was not adequately powered to examine the effect of pulmonary exacerbation on hand contamination. The actual risk of patient-to-patient transmission of CF pathogens within the CF clinic remains difficult to quantify, as long-term observations of many patients utilizing costly methods such as those described in this study would be needed. In addition, patient acquisition of a new respiratory pathogen would not distinguish transmission from the clinic from transmission that occurred during contact elsewhere. Nevertheless, it would appear to be a worthy goal to minimize contamination of CF clinics in ways that are practical and effective without jeopardizing the demonstrated benefits of care provided by CF teams [47]. This study, performed at a variety of CF centers, demonstrated a measurable contamination rate of patients' hands and the clinic environment. We confirmed that the use of alcoholbased hand hygiene products effectively reduced hand carriage of respiratory pathogens, but also found that repeated hand hygiene during office visits is needed to control the risk of recurrent contamination. Acknowledgments The authors thank Drs. Joseph Schwartzman and Gerald O'Connor for input into the design of this study and review of the manuscript. We also thank Drs. Lynne Quittell and Jane Siegel for their helpful comments. We gratefully acknowledge the valuable contributions of Otelah Perry, Torrie Pandora, and Lorrie Hillsgrove from the Dartmouth-Hitchcock Microbiology Laboratory for performance of isolate identification, pulsed field gel electrophoresis and recovery controls. Appendix A. Participating site investigators (alphabetical order) Anne Marie Cairns, Maine Medical Center, Portland, ME; Stanley Fiel, Atlantic Health System, Morristown, NJ; Thomas Lahiri, Fletcher-Allen Medical Center, Burlington, VT; Thomas Lever, Eastern Maine Medical Center, Bangor, ME; H. Worth Parker, Dartmouth-Hitchcock Medical Center, Hanover, NH; Samiya Razvi, Columbia University, New York, NY; Dennis Stokes, Dartmouth-Hitchock Medical Center, Lebanon, NH; Laurie Varlotta, St. Christopher’s Hospital for Children, Philadelphia, PA; Laurie Whittaker, Fletcher-Allen Medical Center Burlington, VT. Research coordinators (alphabetical order) Deborah Conklin, St. Christopher’s Hospital for Children, Philadelphia, PA; Angela Ferro, Fletcher-Allen Medical Center,
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Burlington, VT; David Kissin, Maine Medical Center, Portland, ME; Paula Lomas, Morristown Memorial Hospital, Morristown, NJ; Bonnie Peterson, Dartmouth-Hitchcock Medical Center, Hanover, NH; Amy Savage, Fletcher-Allen Medical Center, Burlington, VT; Becky Welch, Eastern Maine Medical Center, Bangor, ME; Julia Zhou, Columbia University, New York, NY. References [1] Adams C, Morris-Quinn M, McConnell F, West J, Lucey B, Shortt C, et al. Epidemiology and clinical impact of Pseudomonas aeruginosa infection in cystic fibrosis using AP-PCR fingerprinting. J Infect 1998;37:151–8. [2] Ojeniyi B, Frederiksen B, Hoiby N. Pseudomonas aeruginosa crossinfection among patients with cystic fibrosis during a winter camp. Pediatr Pulmonol 2000;29:177–81. [3] Schlichting C, Branger C, Fournier JM, Witte W, Boutonnier A, Wolz C, et al. Typing of Staphylococcus aureus by pulsed-field gel electrophoresis, zymotyping, capsular typing, and phage typing: resolution of clonal relationships. J Clin Microbiol 1993;31:227–32. [4] Goerke C, Kraning K, Stern M, Doring G, Botzenhart K, Wolz C. Molecular epidemiology of community-acquired Staphylococcus aureus in families with and without cystic fibrosis patients. J Infect Dis 2000;181:984–9. [5] Govan JR, Brown PH, Maddison J, Doherty CJ, Nelson JW, Dodd M, et al. Evidence for transmission of Pseudomonas cepacia by social contact in cystic fibrosis. Lancet 1993;342:15–9. [6] LiPuma JJ, Dasen SE, Nielson DW, Stern RC, Stull TL. Person-to-person transmission of Pseudomonas cepacia between patients with cystic fibrosis. Lancet 1990;336:1094–6. [7] Pegues DA, Carson LA, Tablan OC, FitzSimmons SC, Roman SB, Miller JM, et al. Acquisition of Pseudomonas cepacia at summer camps for patients with cystic fibrosis. Summer Camp Study Group. J Pediatr 1994;124:694–702. [8] McCallum SJ, Corkill J, Gallagher M, Ledson MJ, Hart CA, Walshaw MJ. Superinfection with a transmissible strain of Pseudomonas aeruginosa in adults with cystic fibrosis chronically colonised by P. aeruginosa. Lancet 2001;358:558–60. [9] Armstrong DS, Nixon GM, Carzino R, Bigham A, Carlin JB, Robins-Browne RM, et al. Detection of a widespread clone of Pseudomonas aeruginosa in a pediatric cystic fibrosis clinic. Am J Respir Crit Care Med 2002;166:983–7. [10] Givney R, Vickery A, Holliday A, Pegler M, Benn R. Methicillin-resistant Staphylococcus aureus in a cystic fibrosis unit. J Hosp Infect 1997;35:27–36. [11] Nadesalingam K, Conway SP, Denton M. Risk factors for acquisition of methicillin-resistant Staphylococcus aureus (MRSA) by patients with cystic fibrosis. J Cyst Fibros 2005;4:49–52. [12] Pegues DA, Schidlow DV, Tablan OC, Carson LA, Clark NC, Jarvis WR. Possible nosocomial transmission of Pseudomonas cepacia in patients with cystic fibrosis. Arch Pediatr Adolesc Med 1994;148:805–12. [13] Holmes A, Nolan R, Taylor R, Finley R, Riley M, Jiang RZ, et al. An epidemic of Burkholderia cepacia transmitted between patients with and without cystic fibrosis. J Infect Dis 1999;179:1197–205. [14] Clode FE, Metherell LA, Pitt TL. Nosocomial acquisition of Burkholderia gladioli in patients with cystic fibrosis. Am J Respir Crit Care Med 1999;160:374–5. [15] Kalish LA, Waltz DA, Dovey M, Potter-Bynoe G, McAdam AJ, Lipuma JJ, et al. Impact of Burkholderia dolosa on lung function and survival in cystic fibrosis. Am J Respir Crit Care Med 2006;173:421–5 Electronic publication 2005 Nov 4. [16] Doring G, Jansen S, Noll H, Grupp H, Frank F, Botzenhart K, et al. Distribution and transmission of Pseudomonas aeruginosa and Burkholderia cepacia in a hospital ward. Pediatr Pulmonol 1996;21:90–100. [17] Bosshammer J, Fiedler B, Gudowius P, von der Hardt H, Romling U, Tummler B. Comparative hygienic surveillance of contamination with
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