Building Communication Networks: International Network for the Study and Prevention of Emerging Antimicrobial Resistance.The emergence of resistance to antimicrobial agent, is becoming a major public health problem worldwide, especially in hospital-acquired infections Hospital-Acquired Infections Definition A hospital-acquired infection is usually one that first appears three days after a patient is admitted to a hospital or other health care facility. . Infectious diseases infectious diseases: see communicable diseases. experts are particularly concerned because organisms resistant to available antimicrobial drugs have been isolated in hospitals worldwide. The extent of antimicrobial-drug resistance in developing countries, where inappropriate antimicrobial usage may be more common, is unknown (1-6). The emergence and spread of these multidrug-resistant pathogens demonstrate that the medical community (including laboratories) may have difficulty isolating and identifying these organisms and that infection control interventions are either not implemented, ineffective, or implemented so late that the organism(s) has become endemic; in these circumstances, infection control strategies are not effective, and transmission continues (7,8). The emergence of infections caused by methicillin-resistant Staphylococcus aureus methicillin-resistant Staphylococcus aureus Methicillin-aminoglycoside resistant Staphylococcus aureus, MRSA An organism with multiple antibiotic resistances–eg, aminoglycosides, chloramphenicol, clindamycin, erythromycin, rifampin, tetracycline, (MRSA MRSA Methicillin-resistant Staphylococcus aureus. See MARSA. ) vividly demonstrates this failure in infection control. MRSA emerged in Europe nearly 35 years ago concomitantly with the introduction of methicillin methicillin /meth·i·cil·lin/ (meth?i-sil´in) a semisynthetic penicillin highly resistant to inactivation by penicillinase; used as the sodium salt. meth·i·cil·lin n. ; subsequently, during the raid1980s, epidemic strains spread in hospitals throughout the world. In many hospitals, few, if any, infection control precautions were implemented until recently, by which time these strains had become endemic, with infection rates approaching one per 100 admissions (9-12). The large reservoir of MRSA-colonized or -infected patients at these hospitals complicates infection control interventions. Epidemiologic studies on antimicrobial resistance have alerted the medical and public health communities about the importance of emergence of antimicrobial resistance. However, most data on antimicrobial-resistant pathogens were collected as part of studies sponsored by the pharmaceutical industry, and most of the studies were methodologically flawed; thus, the data were not useful for generalizations about antimicrobial resistance in hospitals. In addition, in many countries, a close interrelationship in·ter·re·late tr. & intr.v. in·ter·re·lat·ed, in·ter·re·lat·ing, in·ter·re·lates To place in or come into mutual relationship. in does not exist between the laboratory identifying multidrug-resistant pathogens and the infection control personnel responsible for the prevention and control of transmission of such isolates. Furthermore, many laboratory-based surveillance systems are designed for making patient treatment decisions; the data are not organized in a way that can be used to design and implement control and prevention interventions. With the development of the Emerging Infections Plan at the Centers for Disease Control and Prevention Centers for Disease Control and Prevention (CDC), agency of the U.S. Public Health Service since 1973, with headquarters in Atlanta; it was established in 1946 as the Communicable Disease Center. (CDC See Control Data, century date change and Back Orifice. CDC - Control Data Corporation ) and the endorsement and adaptation of this plan by the World Health Organization (WHO), the emergence of antimicrobial resistance has become a public health priority (13,14). Public health authorities in the United States United States, officially United States of America, republic (2005 est. pop. 295,734,000), 3,539,227 sq mi (9,166,598 sq km), North America. The United States is the world's third largest country in population and the fourth largest country in area. and Europe realize that the emergence of antimicrobial-drug resistance is a global problem; no country is spared, and resistant organisms emerging in one country are likely to spread to other countries. With increasing travel and patient movement throughout the world, the situation exists for transmission of multidrug-resistant pathogens from one country or continent to another (15-19). Because of the urgent need for infection control interventions to prevent further emergence of antimicrobial drug-resistant strains and for a rapid distribution of information about emerging organisms, we initiated the International Network for the Study and Prevention of Emerging Antimicrobial Resistance (INSPEAR). The main objectives of INSPEAR are to serve as an early warning system for emerging resistant pathogens, to facilitate rapid distribution of information about emerging multidrug-resistant pathogens to hospitals and public health authorities worldwide, and to serve as a model for the development and implementation of infection control interventions to prevent the emergence or transmission of antimicrobial drug-resistant pathogens in health-care facilities. Another important function of INSPEAR is to assist microbiologists and infection control personnel in hospitals and countries that lack the expertise needed to conduct microbiologic or epidemiologic studies. Background INSPEAR was begun as a collaborative effort between the Hospital Infections Program (CDC) and microbiologists and hospital epidemiologists in the United States and Europe. It is now a consortium of clinical microbiologists, hospital epidemiologists, infectious diseases specialists; experts in the fields of antimicrobial resistance, hospital epidemiology, and computer sciences; public health agencies; and national reference laboratories. One hundred sixty health-care facilities in 40 countries have joined INSPEAR, with 50% of participants in Western Europe Western Europe The countries of western Europe, especially those that are allied with the United States and Canada in the North Atlantic Treaty Organization (established 1949 and usually known as NATO). and 29% in Eastern Europe Eastern Europe The countries of eastern Europe, especially those that were allied with the USSR in the Warsaw Pact, which was established in 1955 and dissolved in 1991. . Recent Activities Since its initiation in 1998, INSPEAR has conducted several activities essential to the implementation of the early warning system, such as the assessment of the way INSPEAR centers diagnose, conduct surveillance, and control infections caused by multidrug-resistant pathogens, as well as proficiency testing to ensure quality testing in laboratories participating in the program. An assessment of MRSA infections, performed in 90 centers, was designed to assess the methods used by bacteriology bacteriology Study of bacteria. Modern understanding of bacterial forms dates from Ferdinand Cohn's classifications. Other researchers, such as Louis Pasteur, established the connection between bacteria and fermentation and disease. laboratories to identify S. aureus The aureus (pl. aurei) was a gold coin of ancient Rome valued at 25 silver denarii. The aureus was regularly issued from the 1st century BC to the beginning of the 4th century AD, when it was replaced by the solidus. , to determine the susceptibility of S. aureus to antimicrobial drugs, and to assess the surveillance and infection control programs in INSPEAR centers. This study revealed many deficiencies: Isolation of vancomycin- and teicoplanin-resistant S. aureus was reported by three centers but was not confirmed, and public health authorities were not alerted. Of the laboratories surveyed, 11% used oxacillin oxacillin /ox·a·cil·lin/ (ok?sah-sil´in) a semisynthetic penicillinase-resistant penicillin used as the sodium salt in infections due to penicillin-resistant, gram-positive organisms. disks with antimicrobial content different from that recommended by the National Committee for Clinical Laboratory Standards or the Comite de L'Antibiogramme de la Societe Francaise de Microbiologie; 20% did not have an internal quality control program; 36% did not participate in external quality control programs; and 14% did not determine MRSA susceptibility to vancomycin vancomycin (văn'kōmī`sĭn), antibiotic resembling penicillin in the way it acts. It is derived from the bacterium Streptomyces orientalis, which was isolated from soil of India and Indonesia. . Of the health-care facilities surveyed, 77% reported surveillance activities; however, only 36.5% determined the incidence rate per admission, and only 23% determined the rate per patient-days; 40% of the facilities did not have an MRSA control program; and 54% did not monitor or control the use of antimicrobial drugs. These data clearly demonstrate the urgent need to strengthen the laboratory and epidemiologic capacities of INSPEAR centers. A proficiency testing study was performed to investigate the ability of INSPEAR centers to detect clinically important resistance phenotypes, to assist centers in establishing reliable methods to detect particular resistances, to validate data from hospital laboratories participating in INSPEAR, and to ensure consistent quality testing in INSPEAR clinical laboratories. Five strains were sent to the 116 participating laboratories: MRSA, hyper-beta-lactamase producing strain of S. aureus, glycopeptide-intermediate Staphylococcus epidermidis Staphylococcus epidermidis Microbiology A coagulase-negative staphylococcus that comprises up to 80% of clinical isolates Infections by S epidermidis , and van A and van B Enterococcus faecalis Enterococcus faecalis is a Gram-positive commensal bacterium inhabiting the gastrointestinal tracts of humans and other mammals.[1] Like other species in the genus Enterococcus, E. . Seventy-six laboratories responded. Most laboratories did well with both S. aureus challenges; however, 60 (79%) had difficulty detecting reduced susceptibility to glycopeptides in staphylococci staph·y·lo·coc·cus n. pl. staph·y·lo·coc·ci A spherical gram-positive parasitic bacterium of the genus Staphylococcus, usually occurring in grapelike clusters and causing boils, septicemia, and other infections. . All laboratories testing van A E. faecalis identified it correctly as vancomycin resistant, but the results for van B E. faecalis varied. Thirty-nine (52%) of 75 laboratories reported susceptible results for vancomycin, but 19% misidentified van B E. faecalis as vancomycin resistant. An assessment is being conducted to determine if participants have modified their testing methods based on the results of the proficiency testing and CDC recommendations. Early Warning System Another reason antimicrobial resistance is uncontrolled is that clinical microbiology Clinical microbiology The adaptation of microbiological techniques to the study of the etiological agents of infectious disease. Clinical microbiologists determine the nature of infectious disease and test the ability of various antibiotics to inhibit or kill laboratories and the medical community often are not aware of emerging resistance and therefore are not prepared. Preparedness implies that potentially emerging events be known, that laboratorians have the capacity to detect emerging resistance and screen rapidly for colonization, that risk factors for emergence be assessed, and that health-care facilities have access to microbiologic and epidemiologic assistance and have the capacities for efficient isolation precautions (e.g., private rooms with handwashing facilities, availability of gloves). Therefore, to coordinate the timely international scientific and public health response to emerging antimicrobial resistance, we designed an early warning system to monitor, analyze, control, and prevent important events in the emergence of antimicrobial resistance at both the global and regional or local levels. Overall, this early warning system should trigger early epidemiologic and microbiologic interventions to assess risk factors for emerging antimicrobial resistance, leading to more effective control. Global Sentinel Events The need to be aware of global sentinel events is leading to an important function of the program: the periodic publication of what INSPEAR members determine by consensus to be important types of antimicrobial resistance heretofore undescribed or of great public health importance (Table 1). Criteria used to arrive at this list included the overall ease of use of the list by most clinical and reference laboratories and the actual and potential public health impact of resistance events based on factors such as pathogen virulence, frequency of infection caused by the pathogen, and absence of other licensed antimicrobial agents Antimicrobial agents Chemical compounds biosynthetically or synthetically produced which either destroy or usefully suppress the growth or metabolism of a variety of microscopic or submicroscopic forms of life. for treating infections caused by the pathogen. This list of events will be updated regularly and will be published and disseminated to national and international surveillance systems.
Table 1. Early warning system: global sentinel events
Microorganism Resistance
Streptococcus spp. Penicillinase, gentamicin,
glycopeptides, fluoroquinolones
S. pneumoniae Vancomycin, third-generation
cephalosporins, new
fluoroquinolones (gemifloxacine,
grepafloxacin, levofloxacin,
trovafloxacin)
Staphylococcus spp. Glycopeptides (high level)
Enterobacteriaceae Carbapenemase
Neisseria meningitidis Penicillinase, chloramphenicol,
cephalosporins, fluoroquinolones
Acinetobacter baumannii Carbapenemase
Salmonella typhi Third-generation cephalosporins,
fluoroquinolones
Haemophilus influenzae Cephalosporins
Brucella spp. Tetracycline, rifampin,
streptomycin
Clostridium difficile Glycopeptides
Clostridium perfringens Penicillinase
Local and Regional Sentinel Events Local and regional sentinel events consist of the first observation of a clinically important form of resistance in a particular locality or region. Such resistant phenotypes may already be well described from other localities or regions of the world (Table 2). The new regional emergence of resistance in an INSPEAR facility may warrant a coordinated response from local or international INSPEAR members to prevent the resistant strains from becoming endemic.
Table 2. Early warning system: local and regional sentinel events
Microorganism Resistance
Staphylococcus aureus Methicillin, intermediate
susceptibility to glycopeptides
Enterococcus spp. Vancomycin
Enterobacteriaceae Extended-spectrum beta-
lactamase-mediated resistance,
carbapenems, fluoroquinolones
Acinetobacter baumannii Carbapenem
Any bacteria All antimicrobials available at
the regional and local settings
Functioning of the Early Warning System The early warning system should function according to according to prep. 1. As stated or indicated by; on the authority of: according to historians. 2. In keeping with: according to instructions. 3. subsidiarity subsidiarity Noun the principle of taking political decisions at the lowest practical level Noun 1. subsidiarity - secondary importance subordinateness , defined as the principle that a central authority should have a subsidiary function, performing only tasks that cannot be performed effectively at a more immediate or local level. When an emerging event is suspected at an INSPEAR center, the national or regional coordinator should be alerted and microbiologic confirmation performed at the local, national, or regional level when possible, or with additional INSPEAR resources (Figure). Once an event is confirmed, the INSPEAR coordinator will be informed and the public health authorities, WHO, and the INSPEAR centers will be notified. At the same time, an epidemiologic investigation will search for additional cases and assess risk factors through cohort or case-control studies, and surveillance will be implemented. As with microbiologic support, epidemiologic investigation will be performed at the local, national, or regional level if possible; if necessary, INSPEAR resources will be provided. In addition, public health authorities, WHO, and INSPEAR centers will be notified so that measures may be immediately implemented if such an event occurs elsewhere. [Figure ILLUSTRATION OMITTED] Responses to Emerging Resistance INSPEAR response may include immediate, specific responses, such as microbiologic support (e.g., confirmation of resistance, studying the mechanism of resistance, molecular typing to determine clonality) or on-site epidemiologic and infection control support (e.g., assistance with outbreak investigation, intervention studies intervention studies, n.pl the epidemiologic investigations designed to test a hypothesized cause and effect relation by modifying the supposed causal factor(s) in the study population. , control measures) (Table 3). The level of response will be determined by local need, importance of the problem, and capacity of INSPEAR members to respond. In addition, the INSPEAR response to emerging resistance will include coordination of longer term studies to improve the methods for detection and control of resistance. Finally, the INSPEAR response will include the education and training of personnel at INSPEAR hospitals.
Table 3. INSPEAR resources
Microbiology Epidemiology
Bacterial identification Surveillance system
Antimicrobial
Resistance, testing, Study design and conduct
and characterization
of mechanisms
Typing Outbreak investigation
Quality control programs Infection prevention
interventions
Proficiency testing Statistical analysis
Training Statistical training
Conclusions INSPEAR is the first international program dedicated to the control of antimicrobial resistance that combines microbiologic and epidemiologic expertise provided by national reference laboratories and public health agencies. This program should facilitate control of novel antimicrobial-resistant pathogens at the time of their emergence and increase the likelihood of controlling and preventing those pathogens before they become endemic. However, as the results of our MRSA survey and proficiency testing indicate, the microbiologic and epidemiologic capacities of health-care facilities worldwide will need to be strengthened if our goal of detection and control of multidrug-resistant pathogens is to be achieved. References (1.) Go E, Urban C, Burns J, Kreiswirth B, Eisner W, Mariano N, et al. Clinical and molecular epidemiology molecular epidemiology Molecular medicine An evolving field that combines the tools of standard epidemiology–case studies, questionnaires and monitoring of exposure to external factors with the tools of molecular biology–eg, restriction endonucleases, of Acinetobacter spp Acinetobacter spp Bacteriology A widely distributed bacterium found in moist hospital environments, which may establish itself in the respiratory flora and on the skin of Pts with prolonged hospitalization, often via contaminated medical instruments–eg, . Infections sensitive only to polymixin and sulbactam. Lancet 1994;344:1329-32. (2.) Richard P, Le Floch R, Chamoux C, Pannier M, Espaze E, Richet H. Pseudomonas aeruginosa Pseudomonas aeruginosa A normal soil inhabitant and human saprophyte that may contaminate various solutions in a hospital, causing opportunistic infection in weakened Pts Clinical Infective endocarditis in IVDAs, RTIs, UTIs, bacteremia, meningitis, 'malignant' outbreak in a burn unit: role of antimicrobials in the emergence of multiply resistant strains. J Infect Dis 1994;170:377-83. (3.) French GL, Shannon KP, Simmons N. Hospital outbreak of Klebsiella pneumoniae Klebsiella pneu·mo·ni·ae n. Friedlander's bacillus. resistant to broad-spectrum cephalosporins Cephalosporins Definition Cephalosporins are medicines that kill bacteria or prevent their growth. Purpose Cephalosporins are used to treat infections in different parts of the body—the ears, nose, throat, lungs, sinuses, and and beta-lactam-beta-lactamase inhibitor combinations by hyperproduction of SHV SHV Shareholder Value SHV Standard High Volume SHV Sheave SHV Steenkolen Handels Vereeniging SHV Shreveport, LA, USA - Regional Airport (Airport Code) SHV Sport Horse Versatility SHV Supersonic/Hypersonic Vehicle SHV Super Hybrid Vehicle 5 beta-lactamase. J Clin Microbiol 1996;34:358-63. (4.) Neuwirth C, Siebor E, Pechinot A, Kazmierczak A. Outbreak of TEM-24-producing Enterobacter aerogenes Enterobacter aerogenes is a Gram-negative, oxidase negative, catalase positive, rod-shaped bacterium. E. aerogenes is a nosocomial pathogen that causes opportunistic skin and tissue infections. in an intensive care unit and dissemination of the extended-spectrum beta-lactamase extended-spectrum beta-lactamase Third generation cephalosporinase Microbiology A beta-lactamase produced by gram-negative enteric bacteria, in particular K pneumoniae and E coli, which are resistant to third-generation cephalosporins. to other members of the family enterobacteriaceae Noun 1. family Enterobacteriaceae - a large family of Gram-negative rod-shaped bacteria of the order Eubacteriales Enterobacteriaceae bacteria family - a family of bacteria . J Clin Microbiol 1996;34:76-9. (5.) Morosini MI, Canton R, Martinez-Beltran J, Negri MC, Perez-Diaz JC, Baquero F,et al. New extended-spectrum TEM-type beta-lactamase from Salmonella enterica Salmonella enterica is a rod shaped, flagellated, Gram-negative bacterium, and a member of the genus Salmonella.[1] Serovars S. enterica has an extraordinarily large number of serovars isolated in a nosocomial nosocomial /noso·co·mi·al/ (nos?o-ko´me-il) pertaining to or originating in a hospital. nos·o·co·mi·al adj. 1. Of or relating to a hospital. 2. outbreak. Antimicrob Agents Chemother 1995;39:458-61. (6.) Pagani L, Luzzaro F, Ronza P, Rossi A, Micheletti P, Porta F, et al. Outbreak of extended spectrum beta-lactamase producing Serratia marcescens Serratia marcescens Microbiology The type-species of the gram-negative Serratia, widely present in the environment, and occasional cause of hospital-acquired infections Asssociations Contaminated fluids, equipment, cleaning solutions, hands, ↓ in an intensive care unit. FEMS FEMS Federation of European Microbiological Societies FEMS Federation of European Materials Societies FEMS Fabrication Engineering Management System FEMS Facility Equipment Maintenance System (PMEL/TMDE) Immunol Med Microbiol 1994;10:39-46. (7.) Johnson DR, Love-Dixon MA, Brown WJ, Levine DP, Downes FP, Hall WN. Delayed detection of an increase in resistant Acinetobacter baumannii Acinetobacter baumannii is a species of pathogenic bacteria which forms opportunistic infections.[1] There have been many reports of drug-resistant A. baumannii infections among American soldiers wounded in Iraq. at a Detroit hospital. Infect Control Hosp Epidemiol 1992;13:394-8. (8.) Meyer KS, Urban C, Eagan JA, Berger BJ, Rahal JJ. Nosocomial outbreak of Klebsiella klebsiella Any of the rod-shaped bacteria that make up the genus Klebsiella. They are gram-negative (see gram stain), thrive better without oxygen than with it, and do not move. K. spp. Infection resistant to late-generation cephalosporins. Ann Intern Med 1993;119:353-8. (9.) Barber M. Methicilin-resistant staphylococci. J Clin Pathol 1961;14:385-93. (10.) Chabbert YA, Baudens JG. Souches de staphylocoques resistants naturellement a la meticilline et a la 5 methyl-3-phenyl-4-iso-oxazyl penicilline (P12). Annales de l'Institut Pasteur (Paris) 1962;103:222-30. (11.) Richet H, Wiesel M, Le Gallou F, Andre-Richer B, Espaze E. Methicillin-resistant Staphylococcus aureus control in hospitals: the French Experience. Infect Control Hosp Epidemiol 1996;17:509-11. (12.) Pittet D, Safran E, Harbarth S, Borst F, Copin P, Rohner P, et al. Automatic alerts for methicillin-resistant Staphylococcus aureus surveillance and control: Role of a hospital information system. Infect Control Hosp Epidemiol 1996;17:496-502. (13.) Baquero F, Task Force of the General Direction for Health Planning of the Spanish Ministry of Health. Antibiotic resistance antibiotic resistance, n the ability of certain strains of microorganisms to develop resistance to antibiotics. antibiotic resistance in Spain: What can be done? Clin Infect Dis 1996;23:819-23. (14.) Centers for Disease Control and Prevention. Addressing emerging infectious disease An emerging infectious disease (EID) is an infectious disease whose incidence has increased in the past 20 years and threatens to increase in the near future. EIDs include diseases caused by a newly identified microorganism or newly identified strain of a known microorganism (e.g. threats: a prevention strategy for the United States. Atlanta, GA: U.S. Department of Health and Human Services Noun 1. Department of Health and Human Services - the United States federal department that administers all federal programs dealing with health and welfare; created in 1979 Health and Human Services, HHS , Public Health Service, 1994. (15.) Vandenbroucke-Grauls CMJE. Methicillin-resistant Staphylococcus aureus control in hospitals: The Dutch experience. Infect Control Hosp Epidemiol 1996;17:512-3. (16.) Faber M, Rosdhal VT. Changing pattern of phage group II Staphylococcus aureus Staphylococcus au·re·us n. A bacterium that causes furunculosis, pyemia, osteomyelitis, suppuration of wounds, and food poisoning. Staphylococcus aureus Staphylococcus pyogenes infection: from community to hospital. Scand J Infect Dis 1993;25:647-53. (17.) Frenay HM, Van Leeuwen WJ, De Neeling AJ, Schot CS, Rost JA, Van Klingeren B. MRSA: Infection spreads between hospitals. BMJ BMJ n abbr (= British Medical Journal) → vom BMA herausgegebene Zeitschrift 1994;308:58-9. (18.) Harbarth S, Romand J, Frei R, Auckenthaler R, Pittet D. Transmission inter- et intrahospitaliere de staphylocoques dores resistants a la meticilline. Schweiz Med Wochenschr 1997;127:471-8. (19.) Cookson B, Johnson AP, Azadian B, Graham Hutchinson JP, Kaufmann M, Woodford N, et al. International inter- and intrahospital patient spread of a multiple antibiotic-resistant strain of Klebsiella pneumoniae. J Infect Dis 1995;171:511-3. Herve M. Richet,(*) Jasmine Mohammed,(*) L. Clifford McDonald,([dagger]) William R. Jarvis,(*) and INSPEAR(1) (*) Centers for Disease Control and Prevention, Atlanta, Georgia, USA; ([dagger]) National Health Research Institute, Taipei, Taiwan (1) D. Pittet, D.F. Brown, A.G. Dean, S. Gordon, I.M. Gould, M. Gubina, P. Heczko, M. Pana, J. Schindler, M.J. Struelens, F. Tenover, J. Vuopio-Varkila, A. Widmer, W. Witte. Dr. Richet is head of hospital epidemiology and clinical bacteriology at the Centre Hospitalier Universitaire de Nantes (France) and professor of microbiology and hospital epidemiology at the Nantes School of Medicine. In 1987, he entered the Epidemic Intelligence Service The Epidemic Intelligence Service is a program of the United States' Centers for Disease Control and Prevention. Established in 1951 due to biological warfare concerns arising from the Korean War, it has become a hands-on two-year postgraduate training program in epidemiology, with at CDC in Atlanta and served as an EIS (1) (Executive Information System) An information system that consolidates and summarizes ongoing transactions within the organization. It provides top management with all the information it requires at all times from internal and external sources. officer with the Hospital Infections Program and later as medical epidemiologist and returned to CDC from 1997 to 2000, where he served as a senior fellow, also with HIP. Address for correspondence: Herve M. Richet, Institut de Biologie des Hopitaux de Nantes, CHU de Nantes, 44093 Nantes cedex 01, France; fax: (33) 2 40 08 38 29; e-mail: herve.richet@chu-nantes.fr |
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