EVALUATION OF THE ANTIMICROBIAL RESISTANCE SURVEILLANCE DATA PUBLISHED IN THE MEDICAL LITERATURE

3. EVALUATION OF THE ANTIMICROBIAL RESISTANCE SURVEILLANCE DATA PUBLISHED IN THE MEDICAL LITERATURE

The perception of antimicrobial resistance as a threat by a growing number of microbiologists, physicians, public health authorities, or scientific societies has led to the implementation of surveillance programs at the local, national, or international levels. However, the continuous emergence of new resistance phenotypes and the spread of multidrug-resistant organisms suggest that those surveillance programs as well as the efforts at controlling those phenomena are

Types of Surveillance Data 411 failing. Therefore, before addressing the issue of how to conduct surveillance

of antimicrobial resistance it seems important to evaluate the characteristics of the existing surveillance programs by answering the following questions. What antimicrobial resistance surveillance activities are conducted? Are the data available/published on antimicrobial resistance predictive/representative of the global situation? Can the available/published data on antimicrobial resistance

be used to intervene or to predict the evolution of this phenomenon?

3.1. Results of the review

To assess if the available surveillance data can serve such purpose, a review of all articles published in the medical literature from January 1, 2000 to October 31, 2000 and indexed in Medline under the key words “surveillance” and “antimicrobial resistance” was performed for a review article published in ASM news (Richet, 2001). The search retrieved 101 articles showing that sur- veillance data were collected in 32 individual countries in Africa, Asia, North and Latin America, Central and Western Europe, and the Pacific Region. Regarding the microorganisms under surveillance, a combination of multiple Gram-negative and Gram-positive bacteria was included in 28% of the surveil- lance programs, followed by Streptococcus pneumoniae (18%); Enterococcus spp. and Escherichia coli (9% each); Salmonella spp. and Haemophilus spp. (5.6% each); a combination of various Gram-negative bacilli, various Enterobacteriaceae, and Staphylococcus aureus (4.4% each); methicillin- resistant S. aureus, coagulase negative staphylococci, Pseudomonas aeruginosa, Vibrio cholerae, and Moraxella catarrhalis (3.3% each). The majority (81%) of the surveillance programs conducted surveillance of three or more different classes of antimicrobials. When only one class of antimicro- bials was surveyed, ␤-lactams were the most common class of antimicrobial surveyed (13.3%), followed by fluoroquinolones (6.7%), cephalosporins (4.4%), glycopeptides (3.3%), aminoglycosides (3.3%), macrolides (3.3%), sulfonamides (2%), penicillins (1%), trimethoprim/sulfamethoxazole (1%).

Bacteremia was the most common infection surveyed and was included in 20% of the surveillance programs followed by respiratory tract infections (14.4%), diarrhea and urinary tract infection (11%), and meningitis (6.7%). In addition, surveillance of colonization was included in six surveillance programs.

The mean number of isolates included in the surveillance programs was 1,772, the median 502 ranging from 66 to 34,530 isolates. Data were collected during a mean of 37 months with a median duration of 24 months ranging from 1 to 156 months.

The setting of the surveillance was not mentioned in more than a third (36.7%) of the reviewed articles. Almost half (47.8%) of the surveillance

412 Hervé M. Richet activities were performed in healthcare facilities and 18% in the community.

More specifically, hospital acquired infections were the object of surveillance in 24.4% of the programs, community acquired infections in 22% of the pro- grams, adults in 15.6% of the programs and animals in 8% of the programs. The characteristics of the individuals/patients under surveillance were men- tioned in only 22 of the articles, those characteristics included hospitalization in intensive care units (10%), HIV infection (4.4%), cancer (3.3%), newborns (2%), transplantation (1%), and immunosuppression (1%).

In 62% of the articles, the only results presented were the rates of resis- tance to the different antimicrobials tested. In the remaining articles, in addi- tion to the resistance rates, the results of additional studies were shown. They included molecular typing of the isolates in 15.6% of the articles, the analysis of risk factors for infections caused by a resistant organism (12%), the genetic analysis of resistance characters (8%), the assessment of mortality (5.6%), the assessment of the relationship between antimicrobial use and antimicrobial resistance (4.4%), evaluation of antimicrobial therapy (2%), and evaluation of control measures (1%).

3.2. Critical evaluation of the surveillance programs

To assess how the published data could be used to implement control and prevention strategies, we used as evaluation criteria the attributes of a surveil- lance program as defined by the CDC (1988b). Evaluation of surveillance sys- tems should promote the best use of public health resources by ensuring that only important problems are under surveillance and that surveillance systems operate efficiently. Among the attributes of a “good surveillance system” are simplicity, flexibility, representativeness, timeliness, and usefulness.

3.2.1. Simplicity

The simplicity of a surveillance system refers to both its structure and ease of operation. This includes the amount and type of information necessary to establish the diagnosis, the number and type of reporting sources, the methods of data transmission, and the number of organizations involved in receiving case reports.

Surveillance of antimicrobial resistance is most often a very simple process since the amount and type of information needed are laboratory data and nowadays, most laboratory data are computerized and supposedly easy to use for surveillance purpose. Most of the surveillance programs included in this review were very simple since they only included laboratory data and the results presented were restricted to the proportion of resistance to various

Types of Surveillance Data 413 antimicrobials. However, regarding surveillance of antimicrobial resistance,

simplicity may be a limitation since, for instance, the sites of the infections and/or the specimens included were not mentioned in 33.3% of the articles and the patients’ characteristics were not presented in 36.7% of the articles.

3.2.2. Flexibility

A flexible surveillance system can adapt to changing information, needs, or operating conditions and accommodate new diseases and health conditions. Flexibility is best judged retrospectively by observing how a system responded to a new demand. An example is the capacity of an S. aureus surveillance sys- tem to accommodate special surveillance for glycopeptide-intermediate or resistant S. aureus.

Flexibility is a very important attribute for antimicrobial resistance surveil- lance programs because they have to detect emerging resistance phenotypes or emerging pathogens. Unfortunately, no early warning system was described and the flexibility of the surveillance systems was never demonstrated.

3.2.3. Representativeness

A surveillance system that is representative, accurately describes the occurrence of a health event over time and its distribution in the population by place and person. Representativeness is assessed by comparing the characteris- tics of reported events to all such actual events. Judgment of the representa- tiveness is possible based on knowledge of characteristics of the population (age, socioeconomic status, geographic location), natural history of the condi- tion, mode of transmission, prevailing medical practices, multiple source of data, and quality of data. Regarding representativeness, there is both good and bad news. The good news is that the global nature of antimicrobial resistance is clearly addressed by the publication of antimicrobial resistance data collected in both developed and developing countries. Even if 18% of the data on antimicrobial resistance came from the United States, antimicrobial resistance data were also provided by lesser developed and even developing countries in Africa, Central and South America, Asia, and Central Europe. Since antimi- crobial resistance is a global problem, these data are valuable because the extent of antimicrobial resistance in developing countries, where inappropriate antimicrobial usage may be more common, was until recently unknown. The spectrum of microorganisms under surveillance was also broad, including pathogens and opportunistic pathogens, although the pathogens were unevenly distributed with some such as S. pneumoniae probably being overrepresented. The bad news is that there was usually little information on the characteristics of the population, the natural history of the conditions such as the modes of

414 Hervé M. Richet transmission, the medical and laboratory practices, and the quality of the data,

was rarely assessed. One problem with the representativeness of antimicrobial resistance surveillance activities is that many of those programs are sponsored by drug companies who will therefore influence the choice of the microorganisms and antimicrobials under surveillance. This may explain why S. pneumoniae was the leading microorganism surveyed and cephalosporins and fluoro- quinolones the leading antimicrobials.

3.2.4. Timeliness

Timeliness reflects the speed or delay between steps in a surveillance sys- tem and may be evaluated in terms of availability of information for disease control, either for immediate control efforts or for long-term program plan- ning. The timeliness of these antimicrobial resistance surveillance programs can be evaluated by looking at the interval between the end of data collection and their publication. The median interval between the end of the data collec- tion and publication was 2 years ranging from 1 year to 5 years. The timeliness of these surveillance programs is probably not optimal since antimicrobial resistance is rapidly evolving and a 2 year delay is probably much too long. The published data probably do not reflect anymore the current state of antimi- crobial resistance.

3.2.5. Usefulness

A surveillance system is useful if it contributes to the prevention and con- trol of adverse health events. A surveillance system can also be useful if it helps determine that an adverse event previously thought to be unimportant is actually important. The evaluation of the usefulness can be done by answering the following questions:

Does the system detect 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 published data (different laboratories, different methods, different microorganisms, different antimicrobials, different settings when they are known, different populations) and the multiplicity of sur- veillance programs make the detection of trends rather difficult. What we can observe through the reviewed publications looks like a puzzle or a series of snap- shots rather than a continuous process or a coherent ensemble.

Does the system provide estimates of the magnitude of morbidity and mortality related to the health problem under surveillance?

Regarding surveillance of antimicrobial resistance, the answer is mostly no since very few studies sought to assess the mortality and there was nothing

Types of Surveillance Data 415 about morbidity or cost.It is obvious that the assessment of mortality, morbid-

ity, or cost associated with antimicrobial resistance is a very difficult task requiring the collection of extensive clinical data including severity of disease scores and the use of sophisticated epidemiologic methods like matched case- control studies. Once again, most laboratories, even when they are computer- ized, receive and store very few clinical data and it is, for instance, usually impossible to assess, with the information present on the laboratory request form, if the infection is hospital or community acquired.

Does the system stimulate epidemiologic research likely to lead to control and prevention?

Control and prevention of antimicrobial resistance requires knowledge of risk factors leading to the emergence of new resistance genes or phenotypes, and knowledge of the modes of transmission of the resistance genes and organ- isms. The most common epidemiologic research performed was molecular typing of isolates in 16% of the articles, genetic analysis of the resistance genes in 8% of the articles, and assessment of the relationship between antimi- crobial use and antimicrobial resistance in 4% of the articles.

Does the system identify risk factors associated with disease occurrence? Risk factors for infections caused by resistant organisms were assessed in only 12% of the studies and the relationship between antimicrobial use and antimicrobial resistance was evaluated in only 4% of the publications. It is obvi- ously difficult to implement efficient control strategies for a disease if the risk factors for this disease are not clearly identified. This is especially difficult for antimicrobial resistance because many factors related to the organism, the host, the therapies, procedures, or precautions may influence the risk of emer- gence and dissemination of antimicrobial resistance genes and/or antimicro- bial resistant organisms.

Does the system permit assessment of the effects of control measures? Only one article presented the results of an evaluation of control measures.

Does the system lead to improved clinical practice by the healthcare providers who are the constituents of the surveillance system?

Because the majority of antimicrobial therapies are prescribed before the susceptibility of the infecting strain is known, the production of epidemiologic data about antimicrobial resistance is essential. Therefore, the most useful benefit of the reviewed articles could be, if timeliness is not an issue, to improve the prescription of antimicrobials by making the prescription evi- dence based.

In conclusion, this review of the literature shows relatively little good news regarding our capacity to control the spread of antimicrobial resistance and this may be explained by the fact that the public health approach is

416 Hervé M. Richet rarely integrated into antimicrobial resistance surveillance activities, as shown

by the fact that the majority of surveillance programs are laboratory based. Very few clinical data are collected and the data obtained by most sur- veillance programs cannot be used to implement control and/or prevention measures.