What are the key principles of preventing gram negative bacteria – Enterobacteriacea?
Enterobacteriaceae (e.g., E. coli, Klebsiella sp, Enterobacter sp, Citrobacter sp., Proteus sp., etc) include a large number of gram negative bacilli that are normal colonizers of the human gastrointestinal tract. Other reservoirs include water, plants, soil, and gastrointestinal tract of other animals. Enterobacteriaceae are the most commonly isolated bacteria from clinical specimens (combining inpatient and outpatient specimens) and comprise 21% of all nosocomial isolates in the Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network (NHSN) surveillance system in 2006-2007. The two most common organisms, Escherichia coli and Klebsiella pneumoniae, account for 15% of all health care infections.
Specifically, this family accounts for 12.4% of catheter-line associated blood stream infections and 12% of all blood stream infections, 34% of all nosocomial urinary tract infections, 18% of surgical site infections, and 23% of ventilator-associated pneumonias.
There is increasing resistance of these enterobacteriaceae to antibiotics, with endemic rates of organisms resistant to quinolones; third and fourth generation cephalosporins due to endemicity of extended spectrum beta-lactamases (ESBLs) and plasmid mediated amp-C type enzymes; and more recently, the resistance to carbapenem antibiotics via the two most common mechanisms – Klebsiella Pneumoniae Carbapenemase (KPC), and New Delhi Metallobetalactamase-1 (NDM-1), which cause resistance to the broadest of all beta-lactam antibiotics. These carbapenem resistant organisms also contain multidrug resistant genetic elements that code for resistance to most other antibiotics.
Only few antimicrobial agents like colistin, tigecycline, and certain aminoglycosides have consistent in-vitro activity against these carbapenem resistant enterobacteriaceae (CRE), with rising reports of organisms resistant to all available antibiotics. CRE are associated with high morbidity and mortality, with few if any antibiotic treatment options currently and in the near future. CRE have demonstrated epidemic potential, spreading rapidly within individual healthcare settings, and across large geographical areas, and are now endemic across the East Coast United States, Israel, Greece, and India/Pakistan.
With few treatment options for patients infected with CRE, infection control to limit spread of these organisms is critical. However, the best methods to prevent spread are complex, and multi-faceted; and scientific data are still being generated. Nevertheless, the most important goal is early detection within a facility or region, and aggressive containment to limit spread of CRE while incidence is low.
The best infection control practices will include use of sensitive detection methods within the microbiology laboratory, rapid communication of the presence and importance of CRE organisms from microbiology to infection control, aggressive hand-washing, contact precautions and cohorting, antibiotic stewardship, monitoring of admissions of patients from high risk environments (nursing homes, long term care facilities, intensive care units, travel history), use of active surveillance to identify colonization, and communication between public health, and other health care facilities.
What are the conclusions of clinical trials and meta-analyses regarding control of gram negative bacteria – Enterobacteriacea?
The majority of studies are in the setting of a common source or person to person outbreak. As a result, the studies are usually retrospective in design; interventions to control enterobactericeae include multiple interventions simultaneously, making it difficult to assess the relative importance of one aspect of infection control over another.
However, key conclusions in an outbreak situation, in particular of CRE, include:
All acute care facilities to establish protocol, in conjuction with Clinical and Laboratory Standards Institute (CLSI) to detect and immediately alert infection control members if identification of enterobacteriaceae non-susceptible (intermediate or resistant) carbapenems
Hand washing of health care workers between patients cannot be overemphasized
Contact precautions, especially gloving
Single room if possible; if not, cohort patients.
Consider dedicated staff to care of CRE patients
Ensure proper care of invasive monitoring equipment; remove all invasive devices as soon as feasible, and as aseptically as possible
Optimize environmental cleaning and room disinfection
Limit use of broad-spectrum antibiotics as part of an antibiotic stewardship program
Use of initial point prevalence survey (active surveillance cultures of rectum/perirectum) to look for carbapenem resistant or non-susceptible enterobactericeae (CRE) colonization in high risk units, or if cases of CRE are identified within a facility
Weekly point prevalence surveys until no new cases identified within facility
Monitor rates of multidrug resistant enterobactericeae imported from outside hospitals, nursing homes, or long term acute care hospitals in order to identify transfer patients who are at highest risk for colonization with these organisms
Communication and cooperation with other health care facilities and public health departments to notify admission and transfer of patients with carbapenem resistant enterobacteriaceae (CRE)
What are the consequences of ignoring infection control practices related to gram negative bacteria – Enterobacteriacea?
The consequences of ignoring infection control practices related to gram negative enterobacteriaceae are dire. Infections with multi-drug resistant enterobacteriaceae, in particular carbapenem resistant enterobacteriaceae (CRE), are associated with high case fatality rates, as high as 58.8% fatality rate for patients in the ICU and 70-80% fatality rate among patients with bacteremia .
In addition, the plasmid-mediated Klebsiella pneumoniae carbapenemase (KPC) gene has been documented to spread rapidly in an institution(s), from one strain to another, and from one species to another, and can spread across a large geographical region, partially due to the emergence and clonal expansion of a dominant strain of KPC-producing Klebsiella pneumoniae designated multi-locus sequence type 258 (ST 258). Among patients who survive infection or remain colonized but asymptomatic from KPC-producing enterobacteriaceae, these patients are likely vectors of dissemination of these organisms to other patients in health care facilities and community.
Therefore, as treatment options are extremely limited and mortality unacceptably high, prevention, early detection, and early aggressive control are crucial.
Summary of current controversies.
1. Topical application of chlorhexadine: Use of chlorhexadine (topical antiseptic) is now being frequently used in a variety of settings- for hand washing, preoperative skin preparation, oral wash for gingivitis, and for bathing of skin. Its use has been shown to decrease rates of blood stream infections by gram positive organisms, and decrease rates of ventilator associated pneumonia in patients who underwent cardiac surgery. Recent outbreak investigations have used chlorhexadine baths as a part of their multifaceted infection control practices. However, evidence as of yet does not support routine use of chlorhexadine baths or oral solution to decrease rates of infection due to enterobacteriaceae.
2. Selective decontamination of the digestive tract: by orally administering non-absorbable antimicrobial agents has as its aim to prevent or eliminate gut colonization with pathogenic gram negative bacteria, with the goal to decrease rates of infections and mortality. The largest randomized study in ventilated patients in the ICU did show statistically significant decreases in ventilator associated pneumonias and mortality, with transient declines in colonization with multidrug resistant enterobacteriaceae during the 6-month period. However, once the study had concluded, the same units demonstrated rapid rise in multidrug resistant gram negative bacteria. Other studies have showed that in areas of high prevalence of MRSA and VRE, selective decontamination increases rates of infection and colonization with gram positive organisms. Therefore, widespread use of selective decontamination cannot be justified at his time. However, it may have a role to help limit an outbreak due to multidrug resistant enterobacteriaceae, including CRE, though data remains limited.
What is the impact of gram negative bacteria – Enterobacteriacea infections and the need for control relative to infections at other sites or from other specific pathogens?
Enterobacteriaceae are the most frequently isolated group of bacteria when outpatient and inpatient clinical specimens are combined. The family also accounts for 21% of all pathogens isolated in 2006-2007 NHSN surveillance system, which has steadily declined from 42% in 1980-1982, primarily driven by decreased rates of E. coli.
Conversely, gram positive organisms, such as Staphylococci and enterococcal species, have become more predominant causes of nosocomial infection since the early 1980’s.
However, despite the lower prevalence of nosocomial infections due to enterobacteriaceae, because of alarming rates of widespread antibiotic resistance, especially to the broadest antibiotics (carbapenems), infection control of these carbapenem resistant enterobacteriaceae (CRE) is of extreme importance. Case reports have been known to document outbreaks of enterobacteriaceae that are resistant to all known antibiotics (including aminoglycosides, colisitin, and tigecycline), raising true concerns for a new pre-antibiotic era.
Overview of clinical trials, meta-analyses, case control studies, case series, and individual case reports related to infection control and gram negative bacteria – Enterobacteriacea.
See Table I for a summary of infection control stategies.
|Study||Setting||Description of infection control practices||Conclusions|
|Munoz-price 2010||Single center, long-term acute care hospital (LTLACH) in Midwest United States, KPC outbreak||1. Admission active surveillance of multiple patient body sites2. Multiple serial rectal point prevalence surveys until no new cases identified3. Daily 2%chlorhexadine gluconate baths of all patients within LTACH4. Contact isolation or cohorting of all colonized/infected patients5. Preemptive contact isolation of patients upon admission, until admission surveillance cultures negative6. Staff education7. Enhanced environmental cleaning and proper cleaning of invasive equipment||Outbreak of single center stopped, with no new cases of transmission within facility|
|Schwaber 2011||Country wide outbreak of KPC in Israel, 27 acute care hospitals||1. Mandatory reporting of every patient with laboratory specimen that grew Carbapenem resistant enterobacteriaceae (CRE)2. Mandatory isolation of hospitalized carriers of CRE3. Strict adherence to contact precautions4. Placement of patients in self-contained units staffed by dedicated nurses5. Creation of national Task Force of Antimicrobial Resistance and Infection Control, with authority to collect information and intervene as necessary||National intervention halted steep increase in incidence, reaching a low incidence in May 2008 of 21% of peak cases (March 2007)|
|Carbonne 2009||Multi-hospital outbreak (7 hospitals), France||1. Limiting transfer of cases and contact patients to other wards2. Cohorting separately cases and contact patients3. Reinforcing hand hygiene and contact precautions4. Systematic screening of contact patients||A year after outbreak, no additional cases identified|
|Ben-David 2010||Large tertiary care center, Israel, with institutional and nation-wide outbreak||1. Contact precautions of all KPC positive patients2. Prevalence of colonization or infection reported daily to hospital management and national coordinator3. KPC positive patients entered into national database4. Admission rectal surveillance cultures of patients in step-down units, and intensive care units5. Weekly rectal surveillance cultures of patients in same units as above6. In other departments, surveillance cultures from patients with epidemiologic links to patient with KPC||Incidence of infection declined 4.7 fold|
|Kochar 2009||ICU study, tertiary care hospital, Brooklyn, New York, endemic KPC in ICUs||1. Contact isolation for all patients with ceftazidime or carbapenem resistant gram-negative bacillus2. Cohorting of KPC positive patients and detected nurses for KPC positive patients3. Enhanced environmental cleaning with quarternary ammonium compound4. Member of infection control service participated on joint medical and/or nursing rounds 5 days per week5. Weekly rectal swabs and upon admission to unit5. Increased number of alcohol hand gels to increase compliance to hand washing||Significantly decreased number of patients with carbapenem resistant K. pneumoniae during intervention period compared to pre-intervention period (3.7+/-1.6 vs. 9.7+/- 2.2; p<.001)|
Controversies in detail.
See Table II and Table III for information about the use of topical chlorhexadine to prevent infection with enterobacteriaceae and selective decontamination of the digestive tract as infection control practice of enterobacteriaceae, respectively.
|Munoz-price 2010||Single center, long term acute care facility, outbreak of KPC||Use of infection control bundle, which included daily 2% chlorhexadine baths of skin||Implementation of bundle able to limit transmission of KPC at single center|
|Bleasdale, 2007||Single center, ICU, 2-arm, crossover clinical trial||Daily 2% chlorhexadine baths of skin with CHG (chlorhexadine gluconate) impregnated cloths of all patients in study unit; daily baths with soap and water for patients in control arm||Despite significant decrease in incidence of gram-positive bacterial isolates regardless of source in CHG arm, no difference was found in incidence of gram negative bacteria between 2 arms.|
|Koeman 2006||5 university hospitals in Netherlands; ICU, consecutive patients needing mechanical ventilation at least for 48hours; randomized double-blind placebo controlled trial||3 arms: CHX arm- 2% chlorhexadine in petroleum jelly; CHX/COL- 2% chlorhexadine + 2% colisitin in petroleum jelly; placebo- petroleum only. Trial medication placed into buccal cavity four times a day||CHX/COL arm had significant reduction in oropharyngeal colonization with both gram-negative and gram-positive organisms, whereas CHX mostly affected gram-positive organisms. No differences in duration of mechanical ventilation, ICU stay or ICU survival was demonstrated|
|Segers 2006||Single center study, Patients scheduled to undergo sternotomy for cardiothoracic surgery eligible for trial; Netherlands, prospective, randomized, double-blind placebo controlled trial||Oropharygneal rinse with 0.12% chlorhexadine gluconate solution and nasal ointment containing chlorhexadine; or oral rinse and nasal ointment with placebo; administered 4 times a day from time of hospitalization until nasogastric tube removed (usually day after surgery)||Despite significant decline in nosocomial infections, lower respiratory tract infections, bacteremias and deep surgical site infections, most of decrease in infections were due to decrease in gram positive organisms. Though p-value not calculated in paper, does not appear to have decrease in enterobacteriaceae causing nosocomial infections|
|Chlebicki 2007||meta-analysis, to assess efficacy of topical chlorhexidine for prevention of ventilator associated pneumonia (VAP)||7 randomized controlled trials evaluating topical chlorhexadine applied to oropharynx versus placebo or standard care for prevention VAP||Relative risk in preventing VAP was 0.74, 26% relative risk reduction in VAP with use of chlorhexadine, with greatest beneficial effect seen in trials limited to cardiac surgery patients. Overall, no statistical difference in mortality|
|Hammond 1992||South Africa, ICU setting, patients likely to require intubation longer than 48 hours||Randomized study. Patients received gel containing amphotericin B, tobramycin and colisitin 2% (SDD arm), or placebo, applied to oral mucosa q6 hours, and solution containing same antibiotics (SDD arm), or placebo, by mouth or nasogastric tube. Cefotaxime x3 days given to all patients, including placebo||Surveillance cultures showed effective decontamination of patients in SDD arm, but incidence of infection not significant changed. Pts in placebo arm have significantly more infections due to Enterobacteriaceae. Both arms showed increase in colonization of the gut with enterococci, and methicillin resistant staph aureus colonization increased in SDD group. No effect on mortality or morbidity|
|de Smet 2009||13 ICUs in Netherlands, prospective, double-blind crossover study using cluster randomization||3 arms: SDD- systemic antibiotics (IV cefotaxime) + topical oral and gastrointestinal (amphoB, tobra, colisitin); SOD- topical oral and gastrointestinal antibiotics only; standard care||After adjusting for covariates, odds ratio for death at day 28 in SOD and SDD groups, compared to standard care were 0.85 (95% CI 0.74-0.99) and 0.83 (95%CI 0.72-0.97), both statistically significant. Pts receiving SDD have lower incidence of ICU-acquired bacteremia with enterobacteriaceae than those receiving SOD. Pts receiving SDD had decreased rates of rectal and oropharyngeal colonization with enterobacteriaceae, and decreased rates of multidrug resistant enterobacteriacae during both the SDD and SOD periods|
|Oostdijk 2010||Follow-up study of the deSmet 2009 study (see above)||Monthly point prevalence surveys of rectal and respiratory samples in all 13 ICUs, comparing results from the intervention period to the pre and post-intervention periods||During the SDD and SOD intervention arms, gram negative bacilli(GNR) resistance to ceftazidime slowly rose in respiratory tract; after SDD intervention, rebound effect of rapid rise in GNR resistance to ceftazidime in the intestinal tract|
|Brun-Buisson 1989||Single center, ICU, tertiary care center in France; outbreak setting of intestinal colonization and infection with multiresistant enterobacteriacae (resistant to third generation cephalosporins and aminoglycosides)||10 week prospective incidence study (group 1), followed by 8 week randomized open trial of intestinal decontamination with polymyxin E, neomycin, and nalidixic acid q6 hours orally or nasgastric tube (group 3) or no prophylaxis (group 2)||Baseline rates (group 1) of intestinal colonization with multidrug resistant strains 19.6%. During intervention, intestinal colonization rate in group 2 (control) 10%; group 3 (decontamination group) 3%. No new cases detected in following 4 months|
|Zuckerman 2010||Single center, Israel, inpatients of hemato-oncology and bone marrow transplant (BMT)unit, during outbreak of carbapenem resistant Klebsiella pneumoniae (CRKP)||Adult patients admitted to the BMT unit, identified as CRKP carriers on surveillance rectal culture, all received oral gentamicin 80mg q.i.d||Among 15 colonized patients, gastrointestinal eradication achieved in 66% (10/15), discontinuation of bacteremia in 62.5 % (5/8) and nosocomial spread of CRKP carrier state ceased|
What national and international guidelines exist related to gram negative bacteria – Enterobacteriacea?
Guidance for control of infections with carbapenem-resistant or carbapenemase-producing Enterobacteriaceae in acute care facilities. MMWR Morb Mortal Wkly Rep 2009
The healthcare Infection Control Practices Advisory Committee. Management of multidrug resistsant orgainsms in healthcare settings. 2006
Carbapenem-non-susceptible Enterobacteriaceae in Europe: conclusion from a meeting of national experts
What other consensus group statements exist, and what do key leaders advise?
Gupta, N, LImbago, BM, Patel, JB, Kallen, AJ. “Carbapenem-resistant enterobacteriaceae: Epidemiology and Prevention”. Clin Infect Dis. vol. 53. 2011. pp. 60-67.
Bilavsky, E, Schwaber, MJ, Carmeli, Y. “How to stem the tide of carbapenase-producing Enterobacteriaceae?: proactive versus reactive strategies”. Curr Opin Infect Dis. vol. 23. 2010. pp. 327-331.
Carmeli, Y, Akova, M, Cornaglia, G. “Controlling the spread of carbapenemase-producing Gram-negatives: therapeutic approach and infection control”. Clin Micro and Infect. vol. 16. 2010. pp. 102-111.
Kelley, MT, Brenner, DJ, Farmer, JJ, Lennette, EH, Balaws, A, Hausler, WJ. “Enterobacteriaceae”. Manual of clinical microbiology. 1085. pp. 263-277.
Hidron, AI, Edwards, JR, Patel, J. “Antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006-2007”. Infect Control Hosp Epidemiol. vol. 29. 2008. pp. 996-1011.
Black, SR, Bonten, M, Weinstein, RA. “Enterobacteriaceae”. Hospital Epidemiology and Infection Control. 2012. pp. 489-519.
Jacoby, GA, Munoz-Price, LS. “The new beta-lactamases”. N Engl J Med. vol. 352. 2005. pp. 380-391.
Nordmann, P, Cuzon, G, Naas, T. “The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria”. Lancet Infect Dis. vol. 9. 2009. pp. 228-36.
Leverstein-Van Hall, MA, Voets, GM, Versteeg, D. “Global spread of New Delhi metallobetalactamase-1”. Lancet Infect Dis. vol. 10. 2010. pp. 830-831.
Queenan, AM, Bush, K. “Carbapenemases: the versatile beta-lactamases”. Clin Microbiol Rev. vol. 20. 2007 Jul. pp. 440-58.
Rice, LB, Carias, LL, Hutton, RA, Rudin, SD, Endimiani, A, Bonomo, RA. “The KQ element, a complex genetic region conferring transferable resistance to carbapenems, aminoglycosides, and fluoroquinolones in Klebsiella pneumoniae”. Antimicrob Agents Chemother. vol. 52. 2008 Sep. pp. 3427-9.
Elemam, A, Rahimian, J, Mandell, W. “Infection with panresistant Klebsiella pneumoniae. A report of 2 cases and a brief review of the literature”. Clin Infect Dis. vol. 49. 2009. pp. 271-274.
Patel, G, Huprikar, S, Factor, SH, Jenkins, SG, Calfee, DP. “Outcomes of Carbapenem-Resistant Klebsiella pneumoniae Infection and the Impact of Antimicrobial and Adjunctive Therapies”. Infect Control Hosp Epidemiol. vol. 29. 2008 Dec. pp. 1099-106.
Borer, A, Saidel-Odes, L, Reisenberg, K. “Attributable Mortality Rate for Carbapenem‐Resistant Klebsiella pneumoniae Bacteremia”. Infect Control Hosp Epidemiol. vol. 30. 2009. pp. 972-976.
Schwaber, MJ, Carmeli, J. “Carbapenem-resistant enterobacteriaceae”. JAMA. vol. 300. 2008. pp. 2911-2913.
“Guidance for Control of Infections with Carbapenem-Resistant or Carbapenemase producing-Enterobacteriaceae in Acute Care Facilities”. MMWR Morb Mortal Wkly Rep. 2009. pp. 256-60.
Gupta, N, LImbago, BM, Patel, JB, Kallen, AJ. “Carbapenem-resistant enterobacteriaceae: Epidemiology and Prevention”. Clin Infect Dis. vol. 53. 2011. pp. 60-67.
Souli, M, Kontopidou, FV, Papadomichelakis, E. “Clinical experience of serious infections caused by Enterobacteriaceae producing VIM-1 metallo-beta-lactamase in a Greek University Hospital”. Clin Infect Dis. vol. 46. 2008. pp. 847
Samuelsen, O, Naseer, U, Tofteland, S. “Emergence of clonally related Klebsiella pneumoniae isolates of sequence type 258 producing plasmid-mediated KPC carbapenemase in Norway and Sweden”. J Antimicrob Chemother. vol. 63. 2009 Apr. pp. 654-8.
Navon-Venezia, S, Leavitt, A, Schwaber, MJ. “First report on a hyperepidemic clone of KPC-3-producing Klebsiella pneumoniae in Israel genetically related to a strain causing outbreaks in the United States”. Antimicrob Agents Chemother. vol. 53. 2009 Feb. pp. 818-20.
Kitchel, B, Rasheed, JK, Patel, JB. “Molecular epidemiology of KPC-producing Klebsiella pneumoniae isolates in the United States: clonal expansion of multilocus sequence type 258”. Antimicrob Agents Chemother. vol. 53. 2009 Aug. pp. 3365-70.
Won, SY, Munoz-Price, LS, Lolans, K. “Emergence and rapid regional spread of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae”. Clin Infect Dis. vol. 53. 2011. pp. 532
Institute. CLS. Performance Standards for Antimicrobial Susceptibility Testing; Nineteenth Informational Supplement.Vol. M100-S19. 2009.
Institute. CLS. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard. 2008.
Bleasdale, S, Trick, WE, Gonzalez, IM. “Effectiveness of Chlorhexidine Bathing to Reduce Catheter-Associated Bloodstream Infections in Medical Intensive Care Unit Patients”. Arch Intern Med. vol. 167. 2007. pp. 2073-2079.
Segers, P, Speekenbrink, RGH, Ubbink, DT. “Prevention of Nosocomial infection in cardiac surgery by decontamination of the nasopharynx and oropharynx with chlorhexidine gluconate: A randomized trial”. JAMA. vol. 296. 2006. pp. 2460-2466.
Chlebicki, MP, Safdar, N. “Topical chlorhexadine for prevention of ventilator-associated pneumonia: a meta-analysis”. Critical Care Medicine. vol. 35. 2007. pp. 595-602.
Munoz-Price, LS, Hayden, MK, Lolans, K. “Successful control of an outbreak of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae at a long-term acute care hospital”. Infect Control Hosp Epidemiol. vol. 31. 2010. pp. 341-7.
de Smet, AM, Klutymans, J, Cooper, BS. “Decontamination of the digestive tract and oropharynx in ICU patients”. N Engl J Med. vol. 360. 2009. pp. 20-31.
Oostdijk, EAN, de Smet, AM, Block, HEM. “Ecological effects of selective decontamination on resistant gram-negative bacterial colonization”. Am J Resp Crit Care Med. vol. 181. 2010. pp. 452-457.
Hammond, JMJ, Potgeiter, PD, Saunders, GL. “Double-blind study of selective decontamination of the digestive tract in intensive care”. The Lancet. vol. 340. 1992. pp. 5-9.
Brun-Buisson, C, Legrand, P, Rauss, A. “Intestinal decontamination for control of nosocomial multi-resistant gram-negative bacilli: Study of an outbreak in an intensive care unit”. Annals of Internal Medicine. vol. 110. 1989. pp. 873-881.
Zuckerman, T, Benyamini, N, Sprecher, H. “SCT in patients with carbapenem resistant Klebsiella Pneumoniae: a single center experience with oral gentamicin for the eradication of carrier state”. Bone Marrow Transplantation. vol. 46. 2011. pp. 1226-1230.
Schwaber, MJ, Lev, B, Israeli, A. “Containment of a country-wide outbreak of carbapenem-resistant Klebsiella pneumoniae in Israeli hospitals via a nationally implemented intervention”. Clin Infect Dis. vol. 52. 2011. pp. 848-55.
Carbonne, A, Thiolet, JM, Fournier, S. “Control of a multi-hospital outbreak of KPC producing Klebsiella pneumoniae type 2 in France, September to October 2009”. Euro Surveill. vol. 15. 2010. pp. 19734
Ben-David, D, Maor, Y, Keller, N. “Potential Role of Active Surveillance in the control of a hospital- wide outbreak of carbapenem resistant Klebsiella pneumoniae infection”. Infect Control Hosp Epidemiol. vol. 31. 2010. pp. 620-626.
Kochar, S, Sheard, T, Tolentino, E. “Success of an infection control program to reduce the spread of carbapenem resistant Klebsiella pneumoniae”. Infect Control Hosp Epidemiol. vol. 30. 2009. pp. 447-452.
Koeman, M, van der Ven, AJAM, Hak, E. “Oral decontamination with chlorhexadine reduces the incidence of ventilator-associated pneumonia”. Am J Resp Crit Care Med. vol. 173. 2006. pp. 1348-1355.
Siegel, JD, Rhinehart, E, Jackson, M. “The healthcare Infection Control Practices Advisory, Committee”. Management of multidrug resistsant orgainsms in healthcare settings. 2006.
Grundmann, H, Livermore, DM, Giske, CG. “Carbapenem-non-susceptible Enterobacteriaceae in Europe: conclusion from a meeting of national experts”. Euro Surveill. vol. 15. 2010. pp. 19711
Bilavsky, E, Schwaber, MJ, Carmeli, Y. “How to stem the tide of carbapenemase-producing Enterobacteriaceae?: proactive versus reactive strategies”. Curr Opin Infect Dis. vol. 23. 2010. pp. 327-331.
Carmeli, Y, Akova, M, Cornaglia, G. “Controlling the spread of carbapenase producing gram-negative: therapeutic approach and infection control”. Clin Microbiol Infect. vol. 16. 2010. pp. 102-111.
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- What are the key principles of preventing gram negative bacteria - Enterobacteriacea?
- What are the conclusions of clinical trials and meta-analyses regarding control of gram negative bacteria - Enterobacteriacea?
- What are the consequences of ignoring infection control practices related to gram negative bacteria - Enterobacteriacea?
- Summary of current controversies.
- What is the impact of gram negative bacteria - Enterobacteriacea infections and the need for control relative to infections at other sites or from other specific pathogens?
- Overview of clinical trials, meta-analyses, case control studies, case series, and individual case reports related to infection control and gram negative bacteria - Enterobacteriacea.
- Controversies in detail.
- What national and international guidelines exist related to gram negative bacteria - Enterobacteriacea?
- What other consensus group statements exist, and what do key leaders advise?