Melissa B. Miller - Cases in Medical Microbiology and Infectious Diseases

5 Figures demonstrating microscopic organism morphology are presented in many of the cases, as are key radiographic, laboratory, clinical, or pathologic findings. They provide important clues in helping you determine the etiology of the patient’s infection. Because many medical schools have abandoned “wet” labs where medical students get to do “hands-on” microbiology, we felt it was important to have a richly illustrated text.

The temptation for many will be to read the case and its accompanying questions and then go directly to reading the answers. You will derive more benefit from this text by working through the questions and subsequently reading the case discussion.

Have fun and good luck!

The accurate diagnosis of infectious diseases often but not always requires the use of diagnostic tests to establish their cause. The utilization of diagnostic tests in the managed care environment is carefully monitored and is frequently driven by standardized approaches to care called “clinical pathways” or “clinical care algorithms.” These pathways include using a predefined set of diagnostic tests for patients who present with signs and symptoms characteristic of certain clinical conditions, such as community-acquired pneumonia. Currently, the Infectious Diseases Society of America has published more than 30 different “practice guidelines” dealing with various infectious diseases, including HIV, tuberculosis, group A streptococcal pharyngitis, diarrheal disease, and pneumonia, from which clinical pathways can be derived. Clinical pathways and practice guidelines fall under the concept of “evidence-based medicine.” Evidence-based medicine relies on review and interpretation of data in the medical literature as a basis for clinical decision making.

In some patients, such as an otherwise healthy child with a rash typical of varicella (chicken pox), the etiology of the infection can be established with a high degree of certainty by physical examination alone. The use of diagnostic testing in this setting would be viewed as wasteful of the health care dollar. On the other hand, a 4-year-old who presents with enlarged cervical lymph nodes and a sore throat should have a diagnostic test to determine whether he or she has pharyngitis due to group A streptococci. The reason why such testing is necessary is that certain viral syndromes are indistinguishable clinically from group A streptococcal pharyngitis. Because group A streptococcal pharyngitis should be treated with an antibiotic to prevent poststreptococcal sequelae, and viral infections do not respond to antibiotics, determining the cause of the infection in this particular case is central to appropriate patient management. Far too often, antibiotics are given without diagnostic testing in a child with a sore throat. As a result, many children with viral pharyngitis are given antibiotics. This inappropriate use of antibiotics increases antibiotic selective pressure. This can result in greater antimicrobial resistance among organisms in the resident microbiota of the throat, such as Streptococcus pneumoniae . In addition, patients may develop antibiotic-associated complications, such as mild to severe allergic reactions or gastrointestinal distress including diarrhea. One of the goals of the fourth edition of this text is to help you think in a cost-effective way about how best to use laboratory resources. As an introduction to this edition, we will present a general overview of the various laboratory approaches that are used in the diagnosis and management of infectious diseases.

The clinical microbiology laboratory must balance the requirements of timeliness with those of accuracy.

As an example, consider the identification of a Gram-negative bacillus from a clinical specimen. If the organism is identified with the use of a commercially available identification system, an identification and an assessment of the probability of that identification will be made on the basis of biochemical test results and a comparison of these results with a database. So, if the result states that the organism is Enterobacter cloacae with 92% probability, the laboratory may very well report this identification. Assuming that the 92% probability figure generated by the commercial system is on target (many commercial systems do a worse job with anaerobic bacteria), this means that there is a probability of 8%, or about 1 time in 12, that this identification will be incorrect.

Certainly, it would be possible for the laboratory to perform additional testing to be more certain of the identification. The problem is that by doing so there would be a delay, perhaps a clinically significant one, in the reporting of the results of the culture. In some cases such a delay is unavoidable (e.g., when the result of the identification in the commercial system is below an arbitrary acceptable probability and manual methods must be used) or clinically essential (e.g., when a specific identification is required and the isolate must be sent to a reference laboratory for identification; an example is Brucella spp., which require prolonged therapy and are potential agents of bioterrorism).

Similarly, the methods most commonly used in the clinical laboratory for susceptibility testing are imperfect. The worst errors, from the clinical point of view, are those in which the laboratory reports an organism as susceptible to a particular antibiotic to which, in fact, it is resistant. In some cases, additional tests are employed to minimize the risk of this occurring. For example, in addition to standard testing using either an automated or a manual method, recommended susceptibility testing of Enterococcus includes the use of Mueller-Hinton agar in which the antibiotic vancomycin is present at a known concentration. Even if the results of the standard susceptibility testing indicate susceptibility to vancomycin, if there is growth of the Enterococcus isolate on the vancomycin-containing Mueller-Hinton plate, the organism is reported as resistant to vancomycin.

Unfortunately, very few such checks exist to correct erroneous bacterial susceptibility assays. In general, there is a delay in the ability of automated susceptibility methods to reliably identify newly described mechanisms of antibiotic resistance. As a result, manual methods are often required. The performance of automated susceptibility testing methods varies, and certain combinations of organism and antibiotic have an unacceptably high error rate. In such cases, backup methods, such as disk diffusion or MIC testing, should be employed. Laboratories with a significant number of susceptibility tests to perform commonly use automated susceptibility methods because of the labor-intensive nature of manual testing and the speed with which automated systems are able to report results—often in a few hours as compared with overnight incubation, as is the case with manual methods.

Diagnostic tests vary in their sensitivityand specificity. As an example, consider a hypothetical STI (sexually transmitted infection) clinic in which the rapid plasma reagin (RPR) test, a screening test for syphilis, is being evaluated in 1,000 patients with genital ulcer disease who are suspected of having primary syphilis:

On the basis of these data, the sensitivity of this test (the true-positive rate, calculated as true-positive results divided by the number of patients with disease) in primary syphilis is 66%. The specificity (1 minus the false-positive rate) is 83%. Note that in this high-prevalence population (the prevalence here is the total number of cases in which primary syphilis is present—640 divided by the total number of individuals, 1,000—and is thus 0.64 or 64%), the predictive value of a positive test is fairly good, at 88%. The positive predictive value of an assay varies with the prevalence of the disease in the population.This is a key point. An example of this in our syphilis serology example in a low-prevalence population will serve to illustrate the point.