Air contamination with bacteria in CF clinics: implications for prevention strategies

Transcription

1 Air contamination with bacteria in CF clinics: implications for prevention strategies Jonathan B. Zuckerman, M.D., Sarah A. Clock, Ph.D., M.P.H., B. Stephen Prato, James J. McDevitt, Ph.D., Juyan Julia Zhou, M.S., M.P.H., Laurie W. Leclair, M.D., F. Lee Lucas, Ph.D., Lisa Saiman, M.D., M.P.H. for the MASC Study Group* *The names and affiliations of the Management of Air and Surface Contamination in CF Clinics (MASC) Investigators are listed in the Acknowledgments. Online Data Supplement

2 MATERIALS AND METHODS Study Centers The trial was conducted at seven CF Foundation-accredited U.S. care centers from October 2010 to August Institutional review boards at each participating center approved the study. Each participant and/or their parent provided written consent and assent (as appropriate). HIPAA-compliant information was entered into a secure online database. Site investigators were surveyed about their outpatient infection control practices. Study Participants Eligible participants had a confirmed diagnosis of CF, were > 6 years old, had a history of sputum production, and infection with Pseudomonas aeruginosa (PA), methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), Stenotrophomonas maltophilia (SM), Achromobacter xylosoxidans (AX) and/or Burkholderia cepacia complex (BCC). Randomization and Structured Office Visit In a room separate from their exam room, participants performed spirometry, in accordance with American Thoracic Society guidelines (E(1) and provided a sputum or oropharyngeal culture (Figure E1). Spirometry was evaluated using appropriate reference equations (E(2, 3). Prior to entering their exam room, participants were randomized (1:1) to wearing (intervention) or not wearing (control) a surgical mask by the coordinating center at Maine Medical Center, E2

3 stratified by center and randomized within center in blocks of 8. The masks used in this study were the child s face mask (Kimberly-Clark #47127) and the Tecnol cone mask for adults (Kimberly-Clark #00152). Site investigators reviewed the presence of specific signs and symptoms to assess participants for pulmonary exacerbation (E(4). Air Sampling Air samples were collected at a flow rate of 28.3 liters per minute onto blood agar culture plates (Beckton Dickinson, Franklin Lakes, NJ) using Andersen N6 single stage viable impactors (Andersen Instruments, Atlanta, GA). Air samplers were placed ~6 feet from participants ~3 feet above the floor. A 10 minute air sampling time permitted collection at multiple time points during each study visit. Air samples were collected in the spirometry room prior to participants entry (background), 20 minutes after participants entry, and 30 minutes after departure. Exam room air samples were collected prior to (background) and 20 minutes after participants entry. Cough Frequency Cough frequency was recorded digitally during spirometry and during the office visit using a wireless digital device (PulmoTrack, isonea, Oceanside, California). A tracheal phonopneumography piezoelectric sensor was placed on the anterior cervical triangle and attached with an acoustic pad. A second sensor was placed over the second intercostal space E3

4 on the anterior chest. A pneumograph belt was snugly secured around the chest at the xyphoid level. A composite cough score, cough frequency index, was defined as the rate of coughs (events per minute) that occurred in isolation or within coughing bouts, defined as continuous coughing with pauses of less than 2 seconds (E(5). Included software with the cough counter was not able to reliably detect coughs under study conditions due to inadequate sensitivity and specificity, so sound files were manually scored for subjects where air contamination occurred and compared to age- and center-matched controls. Selected files were scored for events per minute by a reader blinded to the participants' clinical status, mask allocation and primary study outcome. Air Exchange Measurements Air exchange rates were measured as room air-volume changes per hour (AC/h) in spirometry and exam rooms prior to each study visit by determining the decay rate of carbon dioxide (CO 2 ) tracer gas (E(6). Pressurized CO 2 was released into the room for 5-10 seconds to reach a target concentration ~5,000-8,000 parts per million (ppm) and mixed for 1-2 minutes using a portable fan (C1). Subsequent CO 2 levels (C2) were measured at 1 minute intervals for ~15 minutes using an Extech CO250 Portable Indoor Air Quality CO 2 Meter/Datalogger (Extech Instruments, Nashua, NH). To determine the AC/h, the slope of the best fit line through the natural logarithm of the background-corrected decay was computed using the formula: c 2 = c 1 e -(AC/hr)x t Microbiological Methods E4

5 Participants respiratory specimens were processed in the microbiology laboratories of participating sites according to CF Foundation guidelines (E(7). The air sample blood agar plates were stored at 4 C prior to being transported on ice to the Columbia University core laboratory and incubated for 72 hours at C. Colonies were placed on selective media and identified using mannitol salt and MacConkey Agar (Becton Dickinson), Staphaurex (Remel, Inc., Lenexa, KS), Vitek 2 (biomérieux, Inc., Durham, NC), and Kirby-Bauer discs (Becton Dickinson). Air sample bacterial concentrations were calculated as colony forming units per cubic meter of air ([CFU]/M 3 ) based on laboratory colony counts, sampling time, and air sampler flow rate. Primary and Secondary Outcomes The primary outcome was the difference in the air contamination rate of the exam rooms of participants wearing and not wearing masks. Air contamination was defined as an air sample harboring at least one study organism concordant with the study participant s respiratory culture (from the study visit or cultures obtaining during the past year). Secondary analyses included [1] the overall rate of air contamination; [2] contamination rates during and 30 minutes after spirometry; and [3] the association of contamination rates with pulmonary exacerbations, age, cough frequency, and air exchange rate. Statistical Analysis Based on our previous study (E(8), we assumed that the air contamination rate among participants without masks would be 8% and we hypothesized that masks would reduce the E5

6 rate by 85% to a rate of 1.2%. To detect a difference of this magnitude with 80% power, we calculated that we needed 176 patients per group. We compared the characteristics of participants randomized to the mask group to those of the control group using chi-square or Fisher s exact test, as appropriate, for categorical variables and t-test or their non-parametric equivalent, as appropriate, for ordinal and continuous variables. Air contamination rates were described using proportions and their exact 95% confidence intervals (CI 95 ). Contamination rates within subject/between settings were compared using McNemar's test and contamination rates between groups were compared using Fisher s exact test. The AC/h was compared in the presence and absence of air contamination using the Wilcoxon test of differences in medians and center differences in exchange rates were evaluated by the Kruskal-Wallis test. Cough frequency during spirometry was compared between participants with air contamination detected (cases) versus age- and study site- matched (1:1) participants without air contamination detected (controls) using the paired single tailed t-test, since low cough frequency would not be expected to result in increased air contamination. RESULTS Study Population During the study period, a convenience sample of 303 participants (mean per site 43, range 15-72) was enrolled during CF clinic visits. Fewer than 10% of eligible patients declined participation. Most (74.6%) were adults and the average FEV 1 % predicted was 65%. A minority of participants (14.5%) fulfilled criteria for a pulmonary exacerbation during their enrollment CF E6

7 clinic visit. The pooled prevalence of specific CF pathogens was comparable to that described in CF Centers in the U.S. (9). Study sites had variable infection control practices, particularly in the use of contact precautions for different CF pathogens (Table E1). Mask Use Observations Among the 149 participants randomized to mask use, 103 (73 adults and 30 children) were observed for appropriate mask use. Masks were removed by 3 adults (4.1%) and 1 child (3.3%) and children lifted or touched their masks more frequently than adults did (86.2% vs. 40.0%, respectively, p< 0.01). Participant Characteristics and Air Contamination The frequency of air contamination was similar for adult and pediatric participants (3.9% vs. 4.2%, p =1.0), for participants with or without a pulmonary exacerbation (2.3% vs. 4.3%, p=1.0), and for different organisms (Table E2). Air Exchange Rates The air exchange rate varied considerably within and among study sites (p<0.001, Figure E2). The median exchange rate for rooms contaminated during spirometry was similar to that of non-contaminated rooms, 3.9 AC/h vs. 5.4 AC/h (p=0.43). The frequency of contamination was also similar for rooms with air exchange rates < 5 vs. > 5 per hour (5.2% vs. 3.0%, respectively, p=0.39). E7

8 Cough Frequency Since air contamination was observed most frequently during the time subjects spent in the spirometry room, we speculated that forced expiratory maneuvers and procedure-related cough promotes elaboration of contaminated aerosols. We therefore compared cough frequency of 12 participants with complete cough count data who contaminated spirometry room air (cases) with 12 age and study site-matched controls. Cases and controls were wellmatched (data not shown). A trend toward a higher cough frequency index was observed in case participants compared to control participants (mean 2.95 events/minute vs events/minute, p=0.052). E8

9 ACKNOWLEDGEMENTS Special thanks to families of CF children and adults who participated in the study and whose dedication to research made the trial possible. MASC Participating Centers: Maine Medical Center, Columbia University Medical Center, Morristown Memorial Hospital, Fletcher Allen Health Care Coordinating Center: Maine Medical Center Microbiology Core Support: Lucy Perez Sarah Clock Investigators at Participating Sites (Site Investigators (SI) and Research Coordinators (RC)): Columbia University Medical Center Lisa Saiman (SI) Juyan Julia Zhou (RC) Fletcher Allen Health Care Laurie Leclair (SI) Thomas Lahiri (SI) Joan Lippmann, (RC) Sandra Diehl (RC) Maine Medical Center Ana Cairns (SI) Jonathan Zuckerman (SI) E9

10 Carrie Milliard (RC) Tina Manley (RC) Rebecca Violett (RC) Rhoda Kennedy Dudevoir (RC) Morristown Memorial Hospital Stanley Fiel (SI) Carol Cahill (RC) E10

11 References E1. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J, Force AET. Standardisation of spirometry. The European respiratory journal 2005; 26: E2. Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general U.S. population. American journal of respiratory and critical care medicine 1999; 159: E3. Wang X, Dockery DW, Wypij D, Fay ME, Ferris BG, Jr. Pulmonary function between 6 and 18 years of age. Pediatr Pulmonol 1993; 15: E4. Treggiari MM, Rosenfeld M, Mayer-Hamblett N, Retsch-Bogart G, Gibson RL, Williams J, Emerson J, Kronmal RA, Ramsey BW. Early anti-pseudomonal acquisition in young patients with cystic fibrosis: rationale and design of the EPIC clinical trial and observational study'. Contemp Clin Trials 2009; 30: E5. Lee KK, Matos S, Evans DH, White P, Pavord ID, Birring SS. A longitudinal assessment of acute cough. American journal of respiratory and critical care medicine 2013; 187: E6. Sherman M. Tracer-gas techniques for measuring ventilation in a single zone. Building and Environment 1990; 25: E11

12 E7. Saiman L, Siegel J. Infection control recommendations for patients with cystic fibrosis: microbiology, important pathogens, and infection control practices to prevent patientto-patient transmission. Infect Control Hosp Epidemiol 2003; 24: S6-52. E8. Zuckerman JB, Zuaro DE, Prato BS, Ruoff KL, Sawicki RW, Quinton HB, Saiman L. Bacterial contamination of cystic fibrosis clinics. J Cyst Fibros 2009; 8: E9. Cystic Fibrosis Foundation patient registry Bethesda, MD: Cystic Fibrosis Foundation; E12

13 Table E1. Site Responses to Infection Control Survey Survey Questions YES NO Are contact precautions used for the following patients? All CF patients Burkholderia cepacia complex spp. MRSA Methicillin-susceptible S. aureus All P. aeruginosa Multidrug-resistant P. aeruginosa ONLY 2 (29%) 4 (57%) 4 (57%) 2 (29%) 2 (29%) 3 (43%) 5 (71%) 3 (43%) 3 (43%) 5 (71%) 5 (71%) 4 (57%) Do patients wear masks in CF clinic? 0 7 (100%) Do you have environmental cleaning policies for CF clinic? 7 (100%) 0 Do you discourage socialization in CF clinic? 5 (71%) 2 (29%)

14 Table E2. Participant Characteristics Associated with Air Contamination Air Contamination 95% CI p-value n (%) Age: Adults 18 years (n=232) 9 (3.9) 1.8% - 7.3% 1.00 Children <18 years (n=71) 3 (4.2) 0.9% % Exacerbation: Yes (n=44) 1 (2.3) 0.1% % 1.00 No (n=259) 11 (4.3) 2.1% - 7.5% Respiratory Organism: MSSA or MRSA (n=93) 4 (4.4) 1.3%-10.9% 0.68 PA (n=68) 1 (1.5) 0.01%-8.6% Both (n=131) 7 (5.2) 2.4%-10.8% Neither (n=11) 0 (0.0) KEY: MSSA = Methicillin-sensitive Staphylococcus aureus; MRSA = Methicillin-resistant S. aureus; PA = Pseudomonas aeruginosa. There was one missing air sample in the No Mask" group

15 Figure E1. Flow Diagram for Study Visit Procedures including Air Sample Collection. Participant Flow Procedures Enrollment and Randomization Spirometry Room Baseline air sample prior to patient entry Air exchange measurement Cough counting Spirometry Air sample in the spirometry room Air sample 30 min after patient exit Exam Room (Mask) Exam Room (No Mask) Baseline air sample prior to patient entry Air exchange measurement Cough counting Interview and physical exam Air sample in the exam room

16 Figure E2. Air Exchange Rates by Study Site Air Exchange Rate (AC/h) Site 1 Site 2 Site 3 Site 4 Site 5 Site 6 Site 7 Box and whisker plot of air exchange rates by study site presented as median (interquartile range, range).