bs_bs_banner
SCIENTIFIC LETTER
Prevalence of oropharyngeal antibiotic-resistant flora among residents of aged care facilities: a pilot study CHRISTOPHER D. ETHERTON-BEER,1,2 TIM INGLIS3 AND GRANT WATERER1,4 1 School of Medicine and Pharmacology and Centre for Medical Research and 3School of Pathology and Laboratory Medicine, University of Western Australia and 2Geriatric Medicine and 4Respiratory Medicine, Royal Perth Hospital, Perth, Western Australia, Australia
Residents in 11 long-term care facilities, and presenting to a single tertiary hospital site, were sampled to estimate prevalence of oropharyngeal colonization with resistant Gram-negative bacteria. From 124 residents, only one isolate (0.8%; 95% confidence interval 0.0%, 4.4) was multi-resistant (an extended-spectrum β-lactamase producing Escherichia coli) indicating that different treatment recommendations for respiratory infections in this population may not be justified. Key words: drug resistance, microbial, Gram-negative bacteria, nursing homes, oropharynx. Abbreviations: IQR, interquartile range; mrGNB, multi-resistant Gram-negative bacteria; RACF, residential aged care facility.
Pneumonia is a particularly common clinical problem among residential aged care facility (RACF) residents, and lower respiratory tract infections are associated with a very substantial burden of mortality.1 Recognition that RACF residents presenting with pneumonia might have a higher prevalence of multi-resistant bacteria has led to professional societies including them in separate guidelines for Healthcare Associated Pneumonia.2 However, there are few data to justify this practice, which is associated with a risk of selection of additional ‘super resistant’ bacteria and is therefore a substantial public health issue.3 Residents of Australian aged care facilities are heavy users of emergency departments and frequently require inpatient care.1 Thus, nosocomial spread of multi-resistant flora from residents of RACF to other health system users is also potentially a substantial problem. Although Gram-negative bacteria are rarely reported in the normal oral flora from healthy adults, it has long been known that the aerobic Gramnegative bacteria responsible for many cases of nosocomial pneumonia originate in the person’s own flora.4 Oropharyngeal colonization with Gramnegative bacteria may be promoted by a range of Correspondence: Christopher Etherton-Beer, Level 6 Ainslie House, 48 Murray Street, Perth, WA 6000, Australia. Email: [email protected] Received 13 October 2014; invited to revise 22 November 2014; revised 8 December 2014; accepted 14 March 2015 (Associate Editor: Yuanlin Song).
Article first published online: 4 May 2015 © 2015 Asian Pacific Society of Respirology
demographic and clinical factors including poor dentition,5 altered salivary flow,6 non-oral feeding7 and antibiotic use. Thus, determining the frequency of oropharyngeal colonization with multi-resistant Gram-negative bacteria (mrGNB) is an important first step in formulating appropriate treatment guidelines for patients from RACF presenting with pneumonia. This cross-sectional observational study was approved by the Human Research Ethics Committee of Royal Perth Hospital. All participants provided written informed consent. Residential aged care facilities that were control facilities in a previous randomized controlled study of an educational intervention for dementia care were invited to participate in this study. Recruitment of these facilities has been described in detail previously.8 Of 20 control facilities in the original randomized study, 11 agreed to participate in the present study. In addition to recruiting at care facilities, we also screened residents presenting to a single metropolitan tertiary teaching hospital. Research staff interrogated the patient information system to identify patients, resident in a long-term aged care facility, who were inpatients with a diagnosis of pneumonia. Active comorbid oral pathology that might make specimen collection painful was an exclusion criterion. In addition, we did not screen residents who the facility manager or registered nurse caring for the person perceived would not be able to consent because of severe cognitive or communication impairments, or who were thought to be in the terminal phase of a comorbid illness. All other residents who consented to specimen collection were enrolled. Research staff collected data on: (i) dependency (modified Barthel Index score9), cognition (Mini Mental State Examination10) and oral health (Oral Health Assessment Tool11). Collection of microbiologic specimens comprised (i) supragingival plaque, obtained by curetting from two remaining teeth, or if edentulous, two dentures; (ii) swab from anterior hard palate; and (iii) 1–3 mL undiluted saliva, obtained by pipette. Plaque was suspended in 1.0 mL phosphate buffered saline, then inoculated onto MacConkey agar (i) with no additional antibiotics; (ii) with 10 μg/mL gentamicin and (iii) with 36 μg/mL cefoxitin, all with standard dilutional streak technique. One additional series of MacConkey plates (no Respirology (2015) 20, 1139–1141 doi: 10.1111/resp.12545
1140 antibiotics) was inoculated using a spiral plater to determine bacterial count per mL (colony-forming unit/mL). Palate swabs were eluted into 2.0 mL phosphate buffered saline and processed as for plaque. Saliva was processed as for plaque. Preliminary differentiation of bacterial species used selective phenotypic features, and substrate utilization tests by plate incorporation and multipoint inoculation. Antibiotic susceptibility testing was by standard plate incorporation method in accordance with National Association of Testing Authorities-accredited clinical laboratory procedures. Definitive identification was by multiplex, real-time polymerization chain reaction using primer sets for all major groups of Gramnegative nosocomial pathogens (Escherichia coli, Klebsiella spp., Enterobacter spp., Proteus spp., Pseudomonas aeruginosa). Data were summarized and presented descriptively. Confidence intervals for proportions were calculated using Stata (version 11, StataCorp, College Station, TX, USA). Of 233 potential participants screened at the 11 participating RACF (n = 219) or during a hospital admission (n = 14), samples were collected from 124 residents (117 at RACF; seven in hospital). Participants had a wide range of levels of disability (median Modified Barthel Index score 74 (indicating moderate disability); interquartile range (IQR) 37, 88). Most participants were cognitively intact (median Mini Mental State Examination score 25; IQR 20, 28). Most residents had changes in oral health observed (median Oral Health Assessment Tool score 3; IQR 2, 5). Only four residents’ swabs, all from the same facility, returned Gram-negative bacteria (3.2% of the entire study population (95% CI 0.9%, 8.1%); 18.2% of residents in that facility (95% CI 5.2%, 40.3%)) and one of these carried a multi-resistant strain (0.8% of the entire study population (95% CI 0.0%, 4.4%); 4.5% of residents in that facility (95% CI 0.1%, 22.8%)). That resident’s saliva cultures produced two isolates of extended-spectrum β-lactamase producing E. coli. These results suggest that the general prevalence of oropharyngeal mrGNB in residents of Perth metropolitan RACF may be very low. The upper limit of the 95% CI for prevalence of mrGNB among the participants in this study was 4.4%. There are no data to determine a specific prevalence rate of resistant bacteria that warrants a change in empiric therapy, but prevalence of between 10% and 20% is usually quoted in guidelines for treatment of various infectious diseases, based on expert opinion supported by empiric data (such as mathematical modelling studies) where possible.12,13 Thus, our results suggest that use of broad spectrum antibiotic therapy in people presenting from RACF with lower respiratory tract infection may often be unnecessary. Notwithstanding the low frequency of detection of oropharyngeal mrGNB colonization, our finding that all positive cultures (and the only multi-resistant isolate) were from residents in one facility supports the hypothesis that facility-specific factors may be relevant to oropharyngeal carriage of Gram-negative bacteria among aged care facility residents. The study used a detailed procedure for collection and processing of microbiologic samples, producing Respirology (2015) 20, 1139–1141
CD Etherton-Beer et al.
confidence that false-negative results would have been unlikely. This is a local study and results may not be generalizable to other regions given Perth’s unique population isolation. A volunteer bias (i.e. participating facilities may tend to be those with positive leadership and quality assurance processes), and non-consecutive screening of inpatients (which was determined by research staff availability), further limit generalizability. Residents who could not consent, and those with active oral disease were excluded, and these may be groups with a higher rate of colonization. We focused only on the presence, or absence of mrGNB in the participant’s oropharyngeal microflora. Future work may benefit from a broader microbiome perspective considering other aspects of health of the oral microbiome, including the quantity and diversity of isolates, and factors, such as oral health and antibiotic use, that could contribute to, or promote, carriage of mrGNB. These preliminary data indicate that the general prevalence of oropharyngeal colonization with mrGNB may not be sufficient to justify different treatment recommendations for respiratory infections acquired by residents of local aged care facilities. The low number of isolates may be an underestimate because of the non-representative sample, and indicate that moderately sized studies will be required to draw reliable conclusions about the epidemiology and nosocomial spread of oropharyngeal mrGNB in Australian residential aged care facilities.
Acknowledgements The authors thank Kerri Schoenauer for her assistance with data collection.
REFERENCES 1 Ingarfield SL, Finn JC, Jacobs IG, Gibson NP, Holman CD, Jelinek GA, Flicker L. Use of emergency departments by older people from residential care: a population based study. Age. Ageing 2009; 38: 314–18. 2 Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM Jr, Musher DM, Niederman MS et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin. Infect. Dis. 2007; 44(Suppl. 2): S27–72. 3 Gottlieb T, Nimmo GR. Antibiotic resistance is an emerging threat to public health: an urgent call to action at the Antimicrobial Resistance Summit 2011. Med. J. Aust. 2011; 194: 281–3. 4 Safdar N, Crnich CJ, Maki DG. The pathogenesis of ventilatorassociated pneumonia: its relevance to developing effective strategies for prevention. Respir. Care 2005; 50: 725–39. 5 Fourrier F, Duvivier B, Boutigny H, Roussel-Delvallez M, Chopin C. Colonization of dental plaque: a source of nosocomial infections in intensive care unit patients. Crit. Care Med. 1998; 26: 301–8. 6 Palmer LB, Albulak K, Fields S, Filkin AM, Simon S, Smaldone GC. Oral clearance and pathogenic oropharyngeal colonization in the elderly. Am. J. Respir. Crit. Care Med. 2001; 164: 464–8. 7 Leibovitz A, Dan M, Zinger J, Carmeli Y, Habot B, Segal R. Pseudomonas aeruginosa and the oropharyngeal ecosystem of tube-fed patients. Emerg. Infect. Dis. 2003; 9: 956–9. © 2015 Asian Pacific Society of Respirology
Oral Gram-negatives in aged care 8 Beer CD, Horner B, Almeida OP, Scherer S, Lautenschlager NT, Bretland N, Flett P, Schaper F, Flicker L. Dementia in residential care: education intervention trial (DIRECT); protocol for a randomised controlled trial. Trials 2010; 11: 63. 9 Shah S, Vanclay F, Cooper B. Improving the sensitivity of the Barthel Index for stroke rehabilitation. J. Clin. Epidemiol. 1989; 42: 703–9. 10 Folstein MF, Folstein SE, McHugh PR. ‘Mini-mental state’. A practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res. 1975; 12: 189–98. 11 Chalmers J, King P, Spencer A, Wright F, Carter K. The oral health assessment tool—validity and reliability. Aust. Dent. J. 2005; 50: 191–9.
© 2015 Asian Pacific Society of Respirology
1141 12 Kaplan SL. Treatment of community-associated methicillinresistant Staphylococcus aureus infections. Pediatr. Infect. Dis. J. 2005; 24: 457–8. 13 Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, Moran GJ, Nicolle LE, Raz R, Schaeffer AJ et al. Executive summary: international clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the infectious diseases society of America and the European society for microbiology and infectious diseases. Clin. Infect. Dis. 2011; 52: 561–4.
Respirology (2015) 20, 1139–1141
SCIENTIFIC LETTER
Prevalence of oropharyngeal antibiotic-resistant flora among residents of aged care facilities: a pilot study CHRISTOPHER D. ETHERTON-BEER,1,2 TIM INGLIS3 AND GRANT WATERER1,4 1 School of Medicine and Pharmacology and Centre for Medical Research and 3School of Pathology and Laboratory Medicine, University of Western Australia and 2Geriatric Medicine and 4Respiratory Medicine, Royal Perth Hospital, Perth, Western Australia, Australia
Residents in 11 long-term care facilities, and presenting to a single tertiary hospital site, were sampled to estimate prevalence of oropharyngeal colonization with resistant Gram-negative bacteria. From 124 residents, only one isolate (0.8%; 95% confidence interval 0.0%, 4.4) was multi-resistant (an extended-spectrum β-lactamase producing Escherichia coli) indicating that different treatment recommendations for respiratory infections in this population may not be justified. Key words: drug resistance, microbial, Gram-negative bacteria, nursing homes, oropharynx. Abbreviations: IQR, interquartile range; mrGNB, multi-resistant Gram-negative bacteria; RACF, residential aged care facility.
Pneumonia is a particularly common clinical problem among residential aged care facility (RACF) residents, and lower respiratory tract infections are associated with a very substantial burden of mortality.1 Recognition that RACF residents presenting with pneumonia might have a higher prevalence of multi-resistant bacteria has led to professional societies including them in separate guidelines for Healthcare Associated Pneumonia.2 However, there are few data to justify this practice, which is associated with a risk of selection of additional ‘super resistant’ bacteria and is therefore a substantial public health issue.3 Residents of Australian aged care facilities are heavy users of emergency departments and frequently require inpatient care.1 Thus, nosocomial spread of multi-resistant flora from residents of RACF to other health system users is also potentially a substantial problem. Although Gram-negative bacteria are rarely reported in the normal oral flora from healthy adults, it has long been known that the aerobic Gramnegative bacteria responsible for many cases of nosocomial pneumonia originate in the person’s own flora.4 Oropharyngeal colonization with Gramnegative bacteria may be promoted by a range of Correspondence: Christopher Etherton-Beer, Level 6 Ainslie House, 48 Murray Street, Perth, WA 6000, Australia. Email: [email protected] Received 13 October 2014; invited to revise 22 November 2014; revised 8 December 2014; accepted 14 March 2015 (Associate Editor: Yuanlin Song).
Article first published online: 4 May 2015 © 2015 Asian Pacific Society of Respirology
demographic and clinical factors including poor dentition,5 altered salivary flow,6 non-oral feeding7 and antibiotic use. Thus, determining the frequency of oropharyngeal colonization with multi-resistant Gram-negative bacteria (mrGNB) is an important first step in formulating appropriate treatment guidelines for patients from RACF presenting with pneumonia. This cross-sectional observational study was approved by the Human Research Ethics Committee of Royal Perth Hospital. All participants provided written informed consent. Residential aged care facilities that were control facilities in a previous randomized controlled study of an educational intervention for dementia care were invited to participate in this study. Recruitment of these facilities has been described in detail previously.8 Of 20 control facilities in the original randomized study, 11 agreed to participate in the present study. In addition to recruiting at care facilities, we also screened residents presenting to a single metropolitan tertiary teaching hospital. Research staff interrogated the patient information system to identify patients, resident in a long-term aged care facility, who were inpatients with a diagnosis of pneumonia. Active comorbid oral pathology that might make specimen collection painful was an exclusion criterion. In addition, we did not screen residents who the facility manager or registered nurse caring for the person perceived would not be able to consent because of severe cognitive or communication impairments, or who were thought to be in the terminal phase of a comorbid illness. All other residents who consented to specimen collection were enrolled. Research staff collected data on: (i) dependency (modified Barthel Index score9), cognition (Mini Mental State Examination10) and oral health (Oral Health Assessment Tool11). Collection of microbiologic specimens comprised (i) supragingival plaque, obtained by curetting from two remaining teeth, or if edentulous, two dentures; (ii) swab from anterior hard palate; and (iii) 1–3 mL undiluted saliva, obtained by pipette. Plaque was suspended in 1.0 mL phosphate buffered saline, then inoculated onto MacConkey agar (i) with no additional antibiotics; (ii) with 10 μg/mL gentamicin and (iii) with 36 μg/mL cefoxitin, all with standard dilutional streak technique. One additional series of MacConkey plates (no Respirology (2015) 20, 1139–1141 doi: 10.1111/resp.12545
1140 antibiotics) was inoculated using a spiral plater to determine bacterial count per mL (colony-forming unit/mL). Palate swabs were eluted into 2.0 mL phosphate buffered saline and processed as for plaque. Saliva was processed as for plaque. Preliminary differentiation of bacterial species used selective phenotypic features, and substrate utilization tests by plate incorporation and multipoint inoculation. Antibiotic susceptibility testing was by standard plate incorporation method in accordance with National Association of Testing Authorities-accredited clinical laboratory procedures. Definitive identification was by multiplex, real-time polymerization chain reaction using primer sets for all major groups of Gramnegative nosocomial pathogens (Escherichia coli, Klebsiella spp., Enterobacter spp., Proteus spp., Pseudomonas aeruginosa). Data were summarized and presented descriptively. Confidence intervals for proportions were calculated using Stata (version 11, StataCorp, College Station, TX, USA). Of 233 potential participants screened at the 11 participating RACF (n = 219) or during a hospital admission (n = 14), samples were collected from 124 residents (117 at RACF; seven in hospital). Participants had a wide range of levels of disability (median Modified Barthel Index score 74 (indicating moderate disability); interquartile range (IQR) 37, 88). Most participants were cognitively intact (median Mini Mental State Examination score 25; IQR 20, 28). Most residents had changes in oral health observed (median Oral Health Assessment Tool score 3; IQR 2, 5). Only four residents’ swabs, all from the same facility, returned Gram-negative bacteria (3.2% of the entire study population (95% CI 0.9%, 8.1%); 18.2% of residents in that facility (95% CI 5.2%, 40.3%)) and one of these carried a multi-resistant strain (0.8% of the entire study population (95% CI 0.0%, 4.4%); 4.5% of residents in that facility (95% CI 0.1%, 22.8%)). That resident’s saliva cultures produced two isolates of extended-spectrum β-lactamase producing E. coli. These results suggest that the general prevalence of oropharyngeal mrGNB in residents of Perth metropolitan RACF may be very low. The upper limit of the 95% CI for prevalence of mrGNB among the participants in this study was 4.4%. There are no data to determine a specific prevalence rate of resistant bacteria that warrants a change in empiric therapy, but prevalence of between 10% and 20% is usually quoted in guidelines for treatment of various infectious diseases, based on expert opinion supported by empiric data (such as mathematical modelling studies) where possible.12,13 Thus, our results suggest that use of broad spectrum antibiotic therapy in people presenting from RACF with lower respiratory tract infection may often be unnecessary. Notwithstanding the low frequency of detection of oropharyngeal mrGNB colonization, our finding that all positive cultures (and the only multi-resistant isolate) were from residents in one facility supports the hypothesis that facility-specific factors may be relevant to oropharyngeal carriage of Gram-negative bacteria among aged care facility residents. The study used a detailed procedure for collection and processing of microbiologic samples, producing Respirology (2015) 20, 1139–1141
CD Etherton-Beer et al.
confidence that false-negative results would have been unlikely. This is a local study and results may not be generalizable to other regions given Perth’s unique population isolation. A volunteer bias (i.e. participating facilities may tend to be those with positive leadership and quality assurance processes), and non-consecutive screening of inpatients (which was determined by research staff availability), further limit generalizability. Residents who could not consent, and those with active oral disease were excluded, and these may be groups with a higher rate of colonization. We focused only on the presence, or absence of mrGNB in the participant’s oropharyngeal microflora. Future work may benefit from a broader microbiome perspective considering other aspects of health of the oral microbiome, including the quantity and diversity of isolates, and factors, such as oral health and antibiotic use, that could contribute to, or promote, carriage of mrGNB. These preliminary data indicate that the general prevalence of oropharyngeal colonization with mrGNB may not be sufficient to justify different treatment recommendations for respiratory infections acquired by residents of local aged care facilities. The low number of isolates may be an underestimate because of the non-representative sample, and indicate that moderately sized studies will be required to draw reliable conclusions about the epidemiology and nosocomial spread of oropharyngeal mrGNB in Australian residential aged care facilities.
Acknowledgements The authors thank Kerri Schoenauer for her assistance with data collection.
REFERENCES 1 Ingarfield SL, Finn JC, Jacobs IG, Gibson NP, Holman CD, Jelinek GA, Flicker L. Use of emergency departments by older people from residential care: a population based study. Age. Ageing 2009; 38: 314–18. 2 Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM Jr, Musher DM, Niederman MS et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin. Infect. Dis. 2007; 44(Suppl. 2): S27–72. 3 Gottlieb T, Nimmo GR. Antibiotic resistance is an emerging threat to public health: an urgent call to action at the Antimicrobial Resistance Summit 2011. Med. J. Aust. 2011; 194: 281–3. 4 Safdar N, Crnich CJ, Maki DG. The pathogenesis of ventilatorassociated pneumonia: its relevance to developing effective strategies for prevention. Respir. Care 2005; 50: 725–39. 5 Fourrier F, Duvivier B, Boutigny H, Roussel-Delvallez M, Chopin C. Colonization of dental plaque: a source of nosocomial infections in intensive care unit patients. Crit. Care Med. 1998; 26: 301–8. 6 Palmer LB, Albulak K, Fields S, Filkin AM, Simon S, Smaldone GC. Oral clearance and pathogenic oropharyngeal colonization in the elderly. Am. J. Respir. Crit. Care Med. 2001; 164: 464–8. 7 Leibovitz A, Dan M, Zinger J, Carmeli Y, Habot B, Segal R. Pseudomonas aeruginosa and the oropharyngeal ecosystem of tube-fed patients. Emerg. Infect. Dis. 2003; 9: 956–9. © 2015 Asian Pacific Society of Respirology
Oral Gram-negatives in aged care 8 Beer CD, Horner B, Almeida OP, Scherer S, Lautenschlager NT, Bretland N, Flett P, Schaper F, Flicker L. Dementia in residential care: education intervention trial (DIRECT); protocol for a randomised controlled trial. Trials 2010; 11: 63. 9 Shah S, Vanclay F, Cooper B. Improving the sensitivity of the Barthel Index for stroke rehabilitation. J. Clin. Epidemiol. 1989; 42: 703–9. 10 Folstein MF, Folstein SE, McHugh PR. ‘Mini-mental state’. A practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res. 1975; 12: 189–98. 11 Chalmers J, King P, Spencer A, Wright F, Carter K. The oral health assessment tool—validity and reliability. Aust. Dent. J. 2005; 50: 191–9.
© 2015 Asian Pacific Society of Respirology
1141 12 Kaplan SL. Treatment of community-associated methicillinresistant Staphylococcus aureus infections. Pediatr. Infect. Dis. J. 2005; 24: 457–8. 13 Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, Moran GJ, Nicolle LE, Raz R, Schaeffer AJ et al. Executive summary: international clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the infectious diseases society of America and the European society for microbiology and infectious diseases. Clin. Infect. Dis. 2011; 52: 561–4.
Respirology (2015) 20, 1139–1141
