There have been a few important updates on the prevention and control of MDR-GNR from ECCMID, here in Madrid. I thought I’d share a couple of key reflections.
The Journal of Hospital Infection have published a welcome special issue on multidrug-resistant Gram-negative bacteria. The collection includes some updates on epidemiology, staff carriage (again!), clinical microbiology, and patient perspectives on CPE, and is well worth a read.
European Survey of Carbapenemase-Producing Enterobacteriaceae (EuSCAPE) project
The EuSCAPE project aimed to improve understanding of the occurrence and spread of CPE. LINK
About European Antibiotic Awareness Day
European Antibiotic Awareness Day is a European health initiative coordinated by ECDC which aims to provide a platform and support for national campaigns on the prudent use of antibiotics. Each year across Europe, the European Antibiotic Awareness Day is marked by national campaigns on the prudent use of antibiotics during the week of 18 November. Prudent use means only using antibiotics when they are needed, with the correct dose, dosage intervals and duration of the course. Follow the European Antibiotic Awareness Day: #EAAD. http://antibiotic.ecdc.europa.eu
About World Antibiotic Awareness Week
The World Health Organization is leading a global campaign for the first World Antibiotic Awareness Week with the slogan “Antibiotics: Handle with Care”. The campaign calls on individuals, governments and health and agriculture professionals to take action to address this urgent health problem. The first World Antibiotic Awareness Week will take place on 16-22 November. Follow the World Antibiotic Awareness Week: #AntibioticResistance. www.who.int/drugresistance.
Travel is easy, cheap (well, depending on your desire for luxury) and you get to meet some interesting characters on your way. Unfortunately, as this recent study from France just published in Clinical Infectious Diseases shows, some of the species that you interact with may have escaped your attention (unless you’re carrying agar plates or some fancy molecular kit with you).
The authors studied travellers attending five vaccination clinics in France prior to and post-travel looking for acquisition of MDR Enterobacteriaeceae. Over 50% came home with more than they bargained for, smuggling MDROs into France in their colons.
The idea of “source control” – using chlorhexidine to reduce the amount of bacteria on a patient’s skin – makes a lot of sense. There’s mounting evidence that chlorhexidine daily bathing works for Gram-positive pathogens, especially in the ICU.1 For example, one of the first thorough studies of chlorhexidine gluconate (CHG) daily bathing showed that the amount of VRE on the skin, in the environment and transmitted to others were all reduced by implementing CHG daily bathing.2 A number of more recent high-quality studies have provided evidence that CHG daily bathing in the ICU setting helps to prevent the transmission of Gram-positive bacteria (see Table below – although note that studies have not been universally positive for CHG).
Table: Studies evaluating the impact of chlorhexidine daily bathing (with or without other interventions) including data on Gram-negative bacteria.
|Noto 2015 3||ICU||Cluster RCT||Daily CHG||No significant reduction in HCAI (composite measure including CLABSI, CAUTI, VAP and CDI)|
|Derde 2014 4||ICU||Time series analysis||Daily CHG plus hand hygiene||Reduction in all MDROs and MRSA (but not VRE or ESBLs)|
|Seyman 2014 5||ICU||Before-after||Weekly CHG ‘douche’||Reduction in BSI but not CLABSI; slight reduction in Gram-negative BSI (n too small for statistical analysis)|
|Hayden 2014 6||LTAC||Before-after||Bundle (including daily CHG)||Acquisition of CRE fell from 4 to 2 per 100 patient weeks|
|Martínez-Reséndez 2014 7||ICU||Before-after||Daily CHG plus hand hygiene||Reductions in all infections, and in A. baumannii VAP rate|
|Apisarnthanarak 2014 8||ICU||Before-after||Bundle (including daily CHG)||Reductions in a. baumannii infection and colonization|
|Climo 2013 9||ICU||Cluster RCT||Daily CHG||Reductions in MRSA / VRE acquisition and all BSI; BSI mainly CoNS (no significant reduction in Gram-negative BSI or CLABSI)|
|Milstone 2013 10||Paed ICU||Cluster RCT||Daily CHG||BSI reduced; mainly CoNS (no significant reduction in Gram-negative BSI or CLABSI)|
|Munoz-Price 2010 11||LTAC||Before-after||Bundle (including daily CHG)||CRE carriage prevalence fell from 21% to 0%|
|Evans 2010 12||ICU||Before-after||Daily CHG||Rate of CLABSI reduced; A. baumannii colonisation reduced but not significantly|
|Popovich 2009 13||ICU||Before-after||Daily CHG||Rate of CLABSI reduced; A. baumannii infection rate reduced but not significantly|
|Bleasdale 2007 14||ICU||Cross-over||Daily CHG||Number of Gram-negative BSI in each arm too small for analysis|
|Gould 2007 15||ICU||Before-after||Daily CHG + mupirocin||Number of Gram-negatives too small for analysis|
|Camus 2005 16||ICU||RCT||Daily CHG + mupirocin||Number of Gram-negative acquisitions similar in intervention vs. control groups|
The question of whether CHG is effective for the prevention and control of Gram-negative bacteria is rather more complicated. The main issue is that Gram-negative bacteria are less susceptible to CHG than Gram-positive bacteria.17 In theory, this shouldn’t be a problem because the amount of CHG applied to skin (10,000 mg/L) is much higher than the minimum inhibitory concentration (MIC) of most Gram-negative bacteria.17 However, it’s worth noting that the concentration of CHG measured on the skin of patients being treated with CHG in one study was considerably lower than the amount applied (15-312 mg/L before the daily bath and 78-1250 mg/L after the daily bath).18 Nonetheless, in this same study, CHG was found to be effective in reducing the skin burden of CRE on patients in a long-term acute care hospital (see Figure, below).18 So, should CHG bathing be applied to combat MDR-GNR?
Figure: Impact of chlorhexidine gluconate (CHG) daily bathing on skin colonization with KPC-producing K. pneumoniae in 64 long-term acute care patients (difference is statistically significant, p=0.01).
A number of studies have implemented CHG as part of a bundle of interventions to control various MDR-GNR. For example, a team from Thailand found that an intervention aimed at improving environmental hygiene combined with CHG brought an outbreak of A. baumannii under control.8 The National Institute of Health Clinical Center19 has included CHG bathing as a component of a successful CRE control bundle, and the same goes for long-term acute care hospitals.6,11 Meanwhile, a Dutch study found that implementing CHG bathing combined with improving hand hygiene failed to reduce the acquisition rate of ESBL Enterobacteriaceae.4 A Mexican study implemented CHG bathing combined with improved hand hygiene and reported a significant reduction in VAP due to A. baumannii.7 However, in all of these studies, it is not possible to tell whether it was the CHG or another element of the bundle that made the difference (or not, in the case of the Dutch study).
No study has been designed specifically to evaluate the impact of CHG daily bathing alone on the rate of Gram-negative bacteria infection or colonization, although rate of Gram-negative bacterial infection or colonization has been reported in several studies of CHG. A small number of high-quality studies that have evaluated CHG as a single intervention including randomization have failed to demonstrate a reduction on Gram-negative BSIs and CLABSIs (see the Climo9, Mlistone10 and Camus16 data from the Table above). Also, a non-randomised before-after study in a trauma ICU reported a non-significant reduction in Acinetobacter species colonization.12 Several other studies mention the rate of Gram-negative infection or colonization in passing, but the numbers are too small for meaningful statistical analysis (see Seyman,5 Popovich13, Bleasdale,14 and Gould15). Although these studies do not provide convincing evidence that CHG works for Gram-negative bacteria, it’s important to remember that they were not powered to evaluate the impact of CHG on Gram-negative bacteria.
One final point to consider is the potential for the development of CHG resistance. Units using CHG universally have reported an increase in the presence of bacteria with reduced CHG susceptibility.20-22 However, the actual degree of reduced susceptibility is moderate, meaning that the clinical importance of this reduced susceptibility is debatable. It is true to say, though, that the potential for meaningful reduced susceptibility is greater in Gram-negative bacteria than in Gram-positive bacteria due to their higher baseline MIC and manifold mechanisms of resistance to biocides and antibiotics.17
So, does CHG bathing work for Gram-negative bacteria? Based on current data, we simply don’t know.
- Derde LP, Dautzenberg MJ, Bonten MJ. Chlorhexidine body washing to control antimicrobial-resistant bacteria in intensive care units: a systematic review. Intensive Care Med 2012; 38: 931-939.
- Vernon MO, Hayden MK, Trick WE et al. Chlorhexidine gluconate to cleanse patients in a medical intensive care unit: the effectiveness of source control to reduce the bioburden of vancomycin-resistant enterococci. Arch Intern Med 2006; 166: 306-312.
- Noto MJ, Domenico HJ, Byrne DW et al. Chlorhexidine Bathing and Health Care-Associated Infections: A Randomized Clinical Trial. JAMA 2015 in press.
- Derde LP, Cooper BS, Goossens H et al. Interventions to reduce colonisation and transmission of antimicrobial-resistant bacteria in intensive care units: an interrupted time series study and cluster randomised trial. Lancet Infect Dis 2014; 14: 31-39.
- Seyman D, Oztoprak N, Berk H, Kizilates F, Emek M. Weekly chlorhexidine douche: does it reduce healthcare-associated bloodstream infections? Scand J Infect Dis 2014; 46: 697-703.
- Hayden MK, Lin MY, Lolans K et al. Prevention of Colonization and Infection by Klebsiella pneumoniae Carbapenemase-Producing Enterobacteriaceae in Long Term Acute Care Hospitals. Clin Infect Dis 2014 in press.
- Martinez-Resendez MF, Garza-Gonzalez E, Mendoza-Olazaran S et al. Impact of daily chlorhexidine baths and hand hygiene compliance on nosocomial infection rates in critically ill patients. Am J Infect Control 2014; 42: 713-717.
- Apisarnthanarak A, Pinitchai U, Warachan B, Warren DK, Khawcharoenporn T, Hayden MK. Effectiveness of infection prevention measures featuring advanced source control and environmental cleaning to limit transmission of extremely-drug resistant Acinetobacter baumannii in a Thai intensive care unit: An analysis before and after extensive flooding. Am J Infect Control 2014; 42: 116-121.
- Climo MW, Yokoe DS, Warren DK et al. Effect of daily chlorhexidine bathing on hospital-acquired infection. N Engl J Med 2013; 368: 533-542.
- Milstone AM, Elward A, Song X et al. Daily chlorhexidine bathing to reduce bacteraemia in critically ill children: a multicentre, cluster-randomised, crossover trial. Lancet 2013; 381: 1099-1106.
- Munoz-Price LS, Hayden MK, Lolans K et al. Successful control of an outbreak of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae at a long-term acute care hospital. Infect Control Hosp Epidemiol 2010; 31: 341-347.
- Evans HL, Dellit TH, Chan J, Nathens AB, Maier RV, Cuschieri J. Effect of chlorhexidine whole-body bathing on hospital-acquired infections among trauma patients. Arch Surg 2010; 145: 240-246.
- Popovich KJ, Hota B, Hayes R, Weinstein RA, Hayden MK. Effectiveness of routine patient cleansing with chlorhexidine gluconate for infection prevention in the medical intensive care unit. Infect Control Hosp Epidemiol 2009; 30: 959-963.
- Bleasdale SC, Trick WE, Gonzalez IM, Lyles RD, Hayden MK, Weinstein RA. Effectiveness of chlorhexidine bathing to reduce catheter-associated bloodstream infections in medical intensive care unit patients. Arch Intern Med 2007; 167: 2073-2079.
- Gould IM, MacKenzie FM, MacLennan G, Pacitti D, Watson EJ, Noble DW. Topical antimicrobials in combination with admission screening and barrier precautions to control endemic methicillin-resistant Staphylococcus aureus in an Intensive Care Unit. Int J Antimicrob Agents 2007; 29: 536-543.
- Camus C, Bellissant E, Sebille V et al. Prevention of acquired infections in intubated patients with the combination of two decontamination regimens. Crit Care Med 2005; 33: 307-314.
- Stickler DJ. Susceptibility of antibiotic-resistant Gram-negative bacteria to biocides: a perspective from the study of catheter biofilms. J Appl Microbiol 2002; 92 Suppl: 163S-170S.
- Lin MY, Lolans K, Blom DW et al. The effectiveness of routine daily chlorhexidine gluconate bathing in reducing Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae skin burden among long-term acute care hospital patients. Infect Control Hosp Epidemiol 2014; 35: 440-442.
- Palmore TN, Henderson DK. Managing Transmission of Carbapenem-Resistant Enterobacteriaceae in Healthcare Settings: A View From the Trenches. Clin Infect Dis 2013; 57: 1593-1599.
- Horner C, Mawer D, Wilcox M. Reduced susceptibility to chlorhexidine in staphylococci: is it increasing and does it matter? J Antimicrob Chemother 2012; 67: 2547-2559.
- Otter JA, Patel A, Cliff PR, Halligan EP, Tosas O, Edgeworth JD. Selection for qacA carriage in CC22 but not CC30 MRSA bloodstream infection isolates during a successful institutional infection control programme. J Antimicrob Chemother 2013; 68: 992-999.
- Suwantarat N, Carroll KC, Tekle T et al. High prevalence of reduced chlorhexidine susceptibility in organisms causing central line-associated bloodstream infections. Infect Control Hosp Epidemiol 2014; 35: 1183-1186.
Image: John Loo.