Hervé M. Richet is professor of microbiology at the Nantes School of Medicine and Head of the Bacteriology Laboratory and Hospital Epidemilogy Unit at the Centre Hospitalier Universitaire de Nantes, Nantes, France.  

Links to Other ASM Pages:


• Table of Contents
• ASM News Issues

Better Antimicrobial Resistance Surveillance Efforts Are Needed 

Surveys of global surveillance activities help explain why it is proving so difficult to slow the expansion of antimicrobial resistance 

Hervé M. Richet

Because antimicrobial resistance traits are so widely distributed among microorganisms, many clinically important pathogens are resistant to all or nearly all available antimicrobials, making this phenomenon a major public health threat worldwide. Hence, officials at the World Health Organization (WHO), the Centers for Disease Control and Prevention (CDC), and similar organizations consider this phenomenon a priority. However, gaining control over antimicrobial resistance is a major challenge. In developed countries, the increasing complexity of health care delivery systems and efforts to reduce the costs of health care add to that challenge. The challenge extends to less-developed countries, which often lack the basic microbiology and infection control resources that are essential for effective antimicrobial resistance control programs. 

In assessing this challenge several years ago, an ASM task force described an urgent need for better antimicrobial resistance surveillance measures, noting that they are essential for providing a sound, long-term view of the emergence and development of such traits. That recommendation raises several practical questions about what can be expected from surveillance programs and how available surveillance data can be used to keep resistant strains from disseminating and to prevent new resistance phenotypes from emerging. In this context, relevant data need to be collected systematically and shared in a timely fashion with those who “need to know,” as CDC officials have noted. 

Despite wide recognition of these public health concerns, new resistance phenotypes remain on the rise while multidrug-resistant pathogens continue to spread throughout the population, suggesting that current surveillance-based control efforts are failing. To determine whether the underlying surveillance efforts are at fault and need to be improved, several questions need to be addressed: What antimicrobial resistance surveillance activities are being conducted? Are relevant data on antimicrobial resistance available, and are they predictive and representative of the global situation? Are those data useful for predicting the public health impact of this phenomenon and for developing intervention strategies? My survey indicates that the current unevenness among worldwide surveillance efforts and in how different health care facilities diagnose and treat infectious diseases is among the most serious complicating factors that need to be faced if we are to gain better control over multidrug-resistant pathogens. 

Evaluating the Published Antimicrobial Resistance Surveillance Data 

Table 1

In an effort to assess surveillance data, I retrieved 101 articles published between 1 January and 31 October 2000 indexed in Medline under the key words “surveillance” and “antimicrobial resistance.” Of that group, 11 review articles were not included in my survey, which focused on primary surveillance reports. During that 10-month period, those reports included antimicrobial resistance surveillance data from 32 individual countries in Africa, Asia, North and Latin America, Central and Western Europe, and the Pacific Region (Table 1). 

The mean number of countries in each surveillance program was 1.6, the median number 1, ranging from 1 to 10 countries. Nine surveillance programs included laboratories located in several European countries, 11 included laboratories in the United States and Canada, 9 in several South American countries, 2 in several Asian countries, and 2 in countries in the Pacific Ocean region. The number of participating laboratories in each surveillance program also varied, with a range from 1 to 48 and a mean of 11.3. During this period, the SENTRY group was responsible for 14, or 15.6%, of the articles presenting antimicrobial resistance surveillance data.

Table 2

These reports group microorganisms in different ways, with 25 of them describing some combination of multiple gram-negative and gram-positive bacteria, whereas others reported on single pathogens, including 16 reports on Streptococcus pneumoniae; 8 on Enterococcus spp. and on Escherichia coli, 5 on Salmonella spp. and Haemophilus spp., and only one included Candida spp. (Table 2). 

Table 3
Table 4

The majority, or 73, of the programs conducted surveillance of three or more different classes of antimicrobials. When only one class of antimicrobials was surveyed, beta-lactamin (a combination of penicillins and cephalosporins) was the most common class of antimicrobials surveyed, followed by fluoroquinolones, cephalosporins, glycopeptides, aminoglycosides, macrolides, sulfamides, penicillins, trimethoprim/sulfamethoxazole, and antifungal agents (Table 3). Among these reports, bacteremia was cited in 20% of the cases, making it the most common infection surveyed, followed by respiratory tract infections, diarrhea and urinary tract infection, and meningitis (Table 4).

The mean number of isolates included in any one of these surveillance reports was 1,772, but the range extends from 66 to 34,530. Almost half the surveillance activities were performed in health care facilities, and 18% in the community. Although little is usually reported about the patients under surveillance, reasons for mention include hospitalization in intensive care units, HIV infection, infections associated with cancer treatment, transplantation, and immunosuppression (Table 4). 

Table 5
Table 6

Most of the reports restrict their findings to rates of resistance of specific antimicrobials being tested. However, 14 reports included molecular typing of isolates, 11 included an analysis of risk factors for infections caused by a resistant organism, 7 of a genetic analysis of resistance characters, 4 information about the relationship between antimicrobial use and antimicrobial resistance, and 1 evaluated control measures (Table 5).

Evaluating the Surveillance Programs 

Such information provides a useful first step toward evaluating surveillance programs as to whether they meet critical CDC criteria that include simplicity, flexibility, representativeness, timeliness, and usefulness. For instance, CDC recommends that a surveillance system maintain simplicity in terms of its structure and ease of operation. For instance, a laboratory should rely on resistance data from routine tests and test results should be incorporated into computerized databases. Most of the surveillance reports included in this review met this criterion by incorporating straightforward laboratory data describing only resistance to antimicrobials. However, in some circumstances, simplicity may be a limitation when reports fail to describe sites of infections, the type of pathogens, or adequate information about the patients.

Although having a flexible surveillance system is valuable, especially when it comes to detecting emerging resistance phenotypes or pathogens, this survey was not designed to determine whether any of the reports come from programs that include such early warning systems or other mechanisms to ensure their flexibility.

To meet the CDC criterion of being representative, a surveillance system should accurately describe antimicrobial resistance-related incidents and trends, including factors such as time, place, and distribution of events within a population. In judging representativeness, one needs pertinent information describing the population, such as the age, socioeconomic status, and geographic location of its members; the natural history of the disease in question, such as its mode of transmission; prevailing medical practices; and the quality and source of data.

One piece of good news is that the global nature of antimicrobial resistance is widely recognized, leading investigators to collect antimicrobial resistance data in both developed and developing countries. Although nearly one-fifth of the reports within this survey are based on antimicrobial resistance data collected in the United States, many more of them compile data from countries in Africa, Central and South America, Asia, and Central Europe. Given the global nature of antimicrobial resistance, it is of considerable value to collect data representing as wide and diversified a geographic and population base as possible. Moreover, it is especially valuable to have antimicrobial resistance data from developing countries, where inappropriate antimicrobial usage may be more common. Similarly, the spectrum of microbial pathogens for which such data are being collected is also broadly based, including ordinary and opportunistic pathogens, although specific pathogens such as Streptococcus pneumoniae are perhaps overrepresented among these surveyed reports.

The bad news is that few of the reports provide information describing the patient population, the natural history of the infectious disease under surveillance, the local medical and laboratory practices, and the quality of the data. Moreover, many of the reports were sponsored by drug companies, often dictating the choice of pathogens and antimicrobial drugs under surveillance, perhaps explaining how S. pneumoniae so often appears among these reports and why cephalosporins and fluoroquinolones are the leading antimicrobials for which resistance data are being collected. 

Other Factors Affect Evaluation of Resistance Data Reporting 

Another important criterion for antimicrobial resistance surveillance systems is that they collect and release information on a timely basis—if they are to serve immediate control efforts or for long-term program planning needs. One simple means for evaluating timeliness is to look at the interval between the end of data collection and publication of reports. The median interval in this survey comes to 2 years, with report publication ranging from 1 to 5 years following data collection. Because antimicrobial resistance is developing at such a rapid pace, this interval indicates that the timeliness of these surveillance programs is not optimal. If timeliness is not an issue, surveillance reports can help guide clinicians when they prescribe antimicrobial agents, leading them to administer such drugs at least on a more probabilistic basis.

Another fundamental criterion for judging the value of the current surveillance system is whether it usefully contributes to the prevention and control of adverse health events. One measure of that usefulness is whether the system detects trends signaling changes in the occurrence of diseases. The duration of surveillance, which was relatively short (median 24 months), as well as the fragmentary nature of the data being published, and the multiplicity of such programs make it difficult to detect trends. Indeed, the reviewed publications look like puzzle fragments or a series of snapshots rather than a continuous process or a coherent ensemble.

Another important measure of the system is whether it provides reasonably accurate estimates of pertinent morbidity and mortality trends. Regarding antimicrobial resistance, most surveillance reports provide almost no information about mortality rates and very little in terms of follow-up morbidity or costs. Certainly, documenting such trends is a very difficult task, one that requires investigators to collect extensive clinical data and to use sophisticated epidemiologic methods such as conducting matched case-control studies. Once again, most diagnostic laboratories, even when they are computerized, receive and store very little in terms of clinical data, typically making it impossible to assess whether an infection is hospital or community acquired. 

If a surveillance system helps to stimulate epidemiologic research, it also seems likely to lead to improved control and prevention strategies. To control the development of antimicrobial resistance, investigators generally need to understand risk factors that lead to resistance, modes of transmission of resistance traits, and other features that contribute to the emergence of resistant pathogenic microorganisms. In this survey of surveillance reports, the most common epidemiologic research involved molecular typing of isolates in 16% of the reports, followed by genetic analysis of resistance in 8%, and assessment of relationship between antimicrobial use and antimicrobial resistance in 4%.

Although it is useful for surveillance systems to identify risk factors associated with particular infectious diseases, the surveyed reports did so in only 12% of the cases, and only rarely established a relationship between antimicrobial use and antimicrobial resistance. Here again, it is obviously difficult to implement efficient control strategies of a disease if risk factors for that disease are not clearly identified. This difficulty is especially pronounced for antimicrobial resistance because so many factors can affect its emergence and dissemination. 

Health Care Facilities Worldwide Conduct Surveillance and Control Multidrug-Resistant Organisms 

It is unrealistic to expect the existing surveillance programs to accomplish much in terms of controlling or preventing antimicrobial resistance. However, the failure of these surveillance programs would not be too harmful if local surveillance efforts lead to control measures.

To evaluate the actual impact of such local efforts, we surveyed some of the methods being used by hospitals worldwide to control one of the leading multidrug-resistant pathogens, methicillin-resistant S. aureus (MRSA). This survey looked at methods used by laboratories to determine the susceptibility of S. aureus to antimicrobials, including methicillin; at MRSA surveillance and control programs in these hospitals; and at the incidence of MRSA infections at the International Networks for the Study and Prevention of Emerging Antimicrobial Resistance (INSPEAR) in hospitals and other health care facilities. The survey obtained responses from 90 INSPEAR facilities in 30 countries, including 7 in Africa, 27 in Central Europe, 43 in Western Europe, 6 in South America, 5 in the United States, and 1 each in the Middle East and Asia.

This survey indicates deficiencies throughout the microbiology, epidemiology, and infection control areas among many of these facilities. In microbiology, some of the surveyed laboratories have problems detecting or properly identifying resistance traits. For instance, poor techniques or inadequate methods led 4.5% of the laboratories to report the isolation of vancomycin-resistant S. aureus without confirming this resistance or alerting public health authorities. 

Moreover, when different laboratories use different breakpoints for MRSA, serious potential mistakes can arise. According to this survey, 8 laboratories used oxacillin disks with an antimicrobial content different from the one recommended when determining breakpoints. The French Comité de l'Antibiogramme de la Sociéte Française de Microbiology (CASFM) recommends using 5-mg oxacillin disk, whereas the National Committee for Clinical Laboratory Standards (NCCLS) recommends using a 1-mg oxacillin disk for determining such breakpoints. However, one center supposedly following the CASFM recommendations used a 1-mg disk, while 7 centers that supposedly followed the NCCLS recommendations in fact used  5-mg disks. One way to avoid such mistakes would be for national committees involved in susceptibility testing to reach a consensus on methods and breakpoints. 

In terms of epidemiology, the survey indicates that many of the surveillance programs did not begin to look for MRSA until relatively late during this epidemic. Moreover, most of the time, health care facilities merely calculated the proportion of all S. aureus isolates resistant to methicillin rather than the incidence rate per number of admissions. This approach is better for calculating the incidence rate per number of days of hospitalization, which is particularly useful for making inter- or intra-health care facilities comparisons, and gives a more reliable picture of the extent of the epidemic.

To contain a local MRSA outbreak, a health care facility needs to implement appropriate patient isolation procedures--an effort that requires both knowledge of those measures and adequate resources to implement them. According to our survey, only 55 of the 90 health care facilities employed MRSA control programs, with 31 confining affected patients to private rooms, 56 of them routinely using gloves in encounters with such patients, 40 of them requiring staff to wearing gowns, 48 insisting on health care workers washing hands when visiting patients, and 39 posting isolation signs on patients' doors. This relatively poor compliance with recommended isolation procedures probably reflects inadequate knowledge and resources at the local level.

My informal survey of the recent literature and the more formal INSPEAR survey provide a rather pessimistic assessment of the current performance of surveillance system in terms of its controlling the spread of antimicrobial resistance. Any expectation of control implies that local diagnostic laboratories are capable of detecting antimicrobial resistance and providing information that could be used for implementing control measures. Unfortunately, although the INSPEAR survey shows that many laboratories can detect and identify vancomycin resistance in S. aureus, this information seldom is verified. Moreover, it also fails to be used in early warning systems, which may not even exist in many countries.

The survey also indicates that in developing countries the task of detecting antibiotic resistance sometimes is made more difficult because materials used in testing are not standardized, different “standards” may be in use or misapplied, and there may be difficulties in gaining access to updated information—for instance, laboratories are required to pay for updated NCCLS guidelines. Often, quality control and proficiency testing programs are unavailable locally, and their absence further contributes to irregularities in surveillance efforts. 

Poor Surveillance Can Impede Efforts To Curb Antibiotic Resistance  

These survey findings help to explain why it is proving so difficult to slow the expansion of antimicrobial resistance. Perhaps the underlying reason because a public health approach is so rarely integrated into antimicrobial resistance surveillance activities. For that to happen, more clinical microbiologists should be trained in epidemiology. In addition, the choice of microorganisms and antimicrobials to survey should be based on their relative public health importance, using criteria such as expected numbers of cases, severity of the infectious disease as measured by its mortality rate and case-fatality ratio, medical costs of such infections, and preventability. Moreover, when surveillance programs are being developed, they should be designed to be useful, meaning that they should contribute to the prevention and control of antimicrobial resistance. To do that, microbiologists will have to collect not only laboratory data but the clinical data that is so often missing from surveillance reports.

Providing adequate and appropriate funding for surveillance programs remains a major challenge. In many cases, pharmaceutical companies are financing these surveillance activities—a situation that certainly risks introducing biases into the choice of organisms or antimicrobials to include in specific surveillance efforts and may also keep them from being representative of major trends. In addition, too great a reliance on this sector for funding surveillance programs could lead to some of them being discontinued despite an ongoing public health need for surveillance data. 

To be sure, public health measures to control antimicrobial resistance are costly, and funding them is difficult. Nonetheless, we need local, national, and international surveillance programs, early warning systems, proper training for laboratorians, appropriate quality control programs and proficiency testing, strengthened microbiologic and epidemiologic capacities of health care facilities worldwide, and the capacities to implement infection control activities. This list is far from exhaustive! 

SUGGESTED READING 

Cassell, G. H. 1995. ASM task force urges broad program on antimicrobial resistance. ASM News 61:116-120.

Centers for Disease Control and Prevention. 1988. CDC surveillance update. Centers for Disease Control and Prevention, Atlanta, Ga.

Centers for Disease Control and Prevention. 1988. Guideline for evaluating surveillance systems. CDC, MMWR 1988:37. 

Richet, H., Mohammed J., McDonald L. C., Jarvis W. R. 2001. Building communication networks: The International Network for the Study and Prevention of Emerging Antimicrobial Resistance. Emerging Infectious Diseases 2001;7:319-322.