A Plea for Clinical Relevance in. Microbiology Division, Department of Pathology, Hartford Hospital, 80 Seymour Street, Hartford, Connecticut 06115

Transcription

1 A Plea for Clinical Relevance in Medical Microbiology RAYMOND C. BARTLETT, M.D. Microbiology Division, Department of Pathology, Hartford Hospital, 80 Seymour Street, Hartford, Connecticut ABSTRACT Bartlett, Raymond C: A plea for clinical relevance in medical microbiology. Am. J. Clin. Pathol. 61: , Laboratory costs have increased 229% over a recent five-year period. Public reaction to rising health care costs is resulting in legislative measures to constrain increases in hospital and clinical laboratory budgets. Under diese conditions, continued annual increases in the volume of clinical microbiology will require higher productivity, or deterioration in quality will occur. Lack of automation in this area will place more emphasis on control of utilization. Performance evaluation programs and academicians often have construed that microbiologic examination of specimens be as complete as technology will allow. Not only is this cosdy, but it often results in reporting of clinically irrelevant and misleading information. Recommendations for criteria which will reduce unnecessary microbiologic effort in the evaluation of specimens received from throat, lower respiratory tract, urine, wounds, vagina and cervix, and anaerobic infections are presented. (Key words: Microbiology; Evaluation program.) IT IS REPORTED that over a five-year period hospital costs have risen 126%, but that laboratory costs have soared 229%. 2 In Connecticut public reaction has led to formation of a Hospital Cost Commission, which would be required to approve any portion of a hospital's budget which exceeded by 6% that spent during the previous year. If clinical laboratories are to continue to provide the approximately 10% annual increases in services demanded of them in addition to 5-6% cost of living adjustments for salaries and costs of supplies and services, it is clear that such constraints will require a remarkable increase in productivity or there will be a Received September 26, 1973; accepted for publication December 5, grave risk of deterioration in quality. Automation will make this possible in clinical chemistry and hematology. Some other solution must be found in bacteriology, where instrumentation has not made significant inroads. Those responsible for providing these services in community hospitals and independent laboratories are not gaining practical support from performance evaluation programs and academicians who demand progressively higher standards of "quality." During an era when substantial numbers of microbiology laboratories were unable to identify a culture of Salmonella typhi, better "quality" was a simple tangible objective. Recently, however, a mixed culture containing Hemo-

2 868 BARTLETT A.J.C.P. Vol. 61 philus parahemolyticus was submitted as a throat culture by a nationwide proficiency testing program. Although full credit was awarded to those who reported "mixed throat flora," the speciation and reporting oí Hemophilus parahemolyticus was viewed as preferable because the agent "has been implicated in cases of pharyngitis." A review of literature on the subject failed to provide support for the etiologic role of this agent in acute pharyngitis. l ' 4,5,6,9 This sort of definitive bacteriology not only is expensive and unnecessary, but is clinically misleading. The reporting of multiple species which either are indigenous or of obscure pathogenicity is confusing to the physician, who has enough difficulty keeping up with perpetual revision of bacterial taxonomy and relative pathogenicity of commonly isolated bacteria. There is general agreement that all who are engaged in the delivery of health care must find ways to make more selective use of resources. The microbiologist who would expend laboratory effort to report microbiologic information of an obscure or low order of clinical significance is just as guilty of abuse of these resources as the physician who orders vast numbers of laboratory tests and prolongs hospitalization of a patient to rule out improbable diagnoses. Many state and federal proficiency testing programs are conducted by personnel with more microbiologic than clinical training. Some state programs look to federal programs for guidance. In turn, the federal programs often appear to lack adequate guidance by concerned and knowledgeable physicians. It is much easier to require complete speciation of single or mixed populations of microorganisms in clinical material than it is to define the point at which the cost benefit ratio exceeds economic acceptability. Any definition of "higher quality" should include development of laboratory criteria for evaluation of the potential of a specimen to produce medically useful information, and the reporting of only that information which may have a significant bearing on diagnosis and treatment. If three or four intestinal species are isolated and reported with results of susceptibility testing, this information is of a lesser quality than a report of "mixed intestinal flora." This is because the former report implies to the physician that no other species exist in the culture (almost certainly not true) and encourages use of either a combination of antimicrobials, or toxic broad-spectrum antimicrobials, conclusions that could have been reached by the quicker latter report, which would have been much less expensive for the laboratory to produce. Significant misconception and confusion exists over the reporting and interpretation of bactériologie data from a number of body sites. The following observations are made in the hope that clinicians and those responsible for evaluation of laboratory performance will support microbiologists who are discriminating in the use of laboratory resources to enable provision of high quality information at the lowest possible cost. Throat Belliveau found that Corynebacterium diphtheriae and Streptococcus pyogenes were the only agents that were uniformly accepted as pharyngeal pathogens by a group of authorities whom he queried. 3 When diphtheria, Vincent's infection, or Candida infection is suspected, the etiologic agent may be sought in smear or culture, but this must be requested specifically by the physician. There are insufficient data supporting the pharyngeal pathogenicity of Hemophilus influenzae, D. pneumoniae, Staphylococcus aureus, Enterobacteriaceae, and Pseudomonads to

3 June 1974 CLINICAL RELEVANCE IN MICROBIOLOGY 869 warrant routine detection and reporting from this site. Untold thousands of throat cultures containing mixed, indigenous, and colonizing flora are subject to costly and needless bacteriology, including susceptibility testing, in the nation's clinical laboratories each year. Although most laboratory workers recognize the lack of clinical evidence to support the usefulness of such information in the treatment of acute pharyngitis, some physicians continue to demand this information because it "might be of significance" in the treatment of acute pharyngitis. Pediatricians for many years used the results of throat cultures as an index to the possible bacterial etiology of otitis media and pneumonitis. There is increasing agreement that the high frequency of colonization of the pharynx with Hemophilus influenzae and Diplococcus pneumoniae renders any such assumption a crude gamble. Sputum So many obstacles are placed in the path of a useful microbiologic evaluation of sputum that some have wondered whether routine sputum Gram stain and culture may be more misleading than helpful. Routine examination of lower respiratory secretions collected by a variety of technics at the Hartford Hospital demonstrated that about one-third contained substantial amounts of oropharyngeal material. Except for the presence of vast numbers of Gram-positive diplococci in a highly mucopurulent specimen as an indication of pneumococcal pneumonia, there appears to be little correlation between the presence of other organisms and the etiology of pneumonia. A singular exception is the finding of pleomorphic Gram-negative rods and Gram-positive cocci in foulsmelling sputum, a finding practically diagnostic of anaerobic pulmonary abscess. Pulmonary bacterial infection results from the ingress of normal or colonizing bacterial flora from the pharynx. This may result from aspiration, or defective host defense mechanisms resulting from deficient tracheobronchial mucociliary function, with or without defects in humoral factors. It seems implausible that detection of the presence of pulmonary pathogens should be attempted from sputum when specimens are allowed to traverse the very area from which all of the causative agents originate. Quantitative sputum culture, washing of sputum, tracheal puncture and nasotracheal aspiration have been suggested as alternative methods of collection. Nasotracheal aspiration is the most practical and least dangerous of these. We have observed a reduction of 15 to 4% in the frequency of specimens consisting primarily of oropharyngeal material when collected by this means. All medical students, nurses, bacteriologists, and laboratory technicians have been taught that specimens truly representative of lower respiratory mucous secretion must be obtained and be selectively cultured in the laboratory. Despite this, substantial numbers of inadequate specimens continue to be submitted and processed, with the result that the treatment of potential respiratory tract infection is obfuscated by the reporting of mixed species of potential pathogens which reside in the patient's oropharynx. We instituted a system of routine Gram stain evaluation of the quality of all lower respiratory tract secretions submitted to our laboratory. Scores range from 0 to 3 based on the observed numbers of: squamous epithelial cells (10-25 per 10 X field = -1; >25 per 10 x field = -2; mucus (+1); and neutrophils (10-25 per 10 x field = +1; >25 per 10 X field = +2). Repeat specimens are requested immediately when a score of 0 is obtained, indicating that the material appears to be

4 870 BARTLETT A.J.C.P. Vol. 61 primarily of oropharyngeal origin; specimens with scores of 1-3 are cultured. If more than one potential pathogen is isolated from a specimen obtaining a score of 1 (indicating significant admixture of oropharyngeal material, or minimal evidence of mucopurulent tracheobronchial secretion), these are reported in broad generic terms based on gross inspection of plates. No speciation or susceptibility testing is performed. A statement is appended, "Evidence of oropharyngeal contamination, please repeat." Similarly, from specimens with scores of 2 and 3, no more than two or three potential pathogens are speciated and tested for susceptibility. Unplanted specimens and plates are held for 72 hours in case physicians call to explain circumstances which would justify processing. Such calls are received infrequently. This system resulted in the elimination of speciation and susceptibility testing of 28% of all potential pathogens which were isolated from specimens from lower respiratory tract secretions in our laboratory. This represents a significant saving in unnecessary use of laboratory resources, as well as exclusion of potentially confusing, misleading, and clinically irrelevant information from the patient's record. Urine Most urine specimens contain more than 10 5 or less than 10 2 bacteria per ml. The higher counts are usually associated with urinary tract infection and the lower, with contamination. Few urines with counts in the range bacteria per ml. are observed. There are equal probabilities of infection and contamination at 10 3 bacteria per ml. Urine from patients receiving antimicrobial therapy often will reveal counts between IO 4 and 10 5 bacteria per ml. 8 Complete speciation and susceptibility testing is indicated when one or two isolates are found in numbers greater than 10 4 per ml, or when one isolate is found between 10 3 and Kass has remarked on the significance of mixed cultures. 2 We report specimens as "Probable contamination, please repeat" when three or more isolates in numbers greater than 10 5 per ml are found; or when two or more between 10 3 and 10 4 are found. When urine specimens are collected by suprapubic puncture, cystoscopy, or catheterization, quantitative technic should be extended down to a range of 100 bacteria per ml. Otherwise occasional significant but low bacterial counts will be missed. The risk of low-level contamination from one of these modes of collection is small. Broth culture of urine is unnecessary. It provides no quantification and leads to identification and reporting of insignificant numbers of bacteria. Unfortunately, this is widely practiced in many clinical laboratories. More than with any other type of specimen, insistence should be placed on prevention of delay in transmission of urine specimens. If transit time exceeds one hour, or no time of collection is given, we report "Please submit another specimen; received after prolonged delay." Wounds Recently, a proficiency testing specimen to be treated as a culture of a decubitus ulcer was distributed by a government agency. The culture contained Citrobacter freundii, Escherichia coli, and Serratia marcescens. Laboratories which carefully identified all of the species in this mixed culture were rewarded with a perfect score. The critique stated that "all of these are of clinical significance and should be reported to the physician." Although we speciate and test the antimicrobial susceptibility of as many as three isolates from wound cultures, four or more species of this type would cause us to report "Mixed intestinal flora." Proficiency testing with

5 June 1974 CLINICAL RELEVANCE IN MICROBIOLOGY 871 this type of specimen promotes the impression that definitive bactériologie classification of mixed cultures is important and desirable. The clinical usefulness which can be attached to the isolation, identification and antimicrobial susceptibility testing of isolates representing flora from open wounds, skin, and other sources of gross contamination does not justify the added bactériologie effort. The number of species which are isolated and reported from any specimen is indirectly proportional to the clinical value of the report and directly proportional to the utilization of laboratory resources. A report of mixed growth should be supplemented with a request for repeat collection after removal of superficial and colonizing bacteria. Alternative reporting of predominating species is misleading. This conveys the impression that therapy directed at one or several pathogens will eradicate the infection, when in fact multiple organisms are present and those which were isolated happened to be the most rapidly growing or surviving forms. An exception is the isolation of Streptococcus pyogenes or Staphylococcus aureus. Although these may represent harmless colonization, they may be associated with dangerous infections of underlying soft tissues. The Gram stain is widely neglected and extremely helpful in evaluating the significance of mixed cultures from wounds. Frequently we have observed cultures containing aerobic intestinal flora in which Gram stains demonstrate small pleomorphic Gram-negative rods and Gram-positive cocci which clearly represent a mixed anaerobic infection. Often the Gram stain will provide better evidence than culture for the presence of mixed intestinal flora resulting from leakage of intestinal content. The majority of specimens yielding mixed cultures will on Gram stain show no pyogenic reaction, and only clumps of bacteria with exfoliated epidermal cells. Physicians often rejoin efforts of discriminating microbiologists with: "You just report what is in it; I'll decide whether it is significant or not." The isolation and speciation of all aerobic and anaerobic microorganisms in many specimens submitted with no more information than "wound" would lead to an exhaustive bactériologie exercise which could result in the reporting of a dozen or more isolates. Clearly, definitive bacteriology to be interpreted by the clinician is not the solution. Vagina and Cervix Cultures of material from the vagina and cervix present a problem when they are submitted from patients in whom septic abortion or endometritis is suspected. Etiologic agents are derived from the vaginal flora. As with collection of sputum, which must traverse the pharynx, it seems irrational to collect material from the cervical os, which almost always is contaminated with vaginal flora, to determine whether any of these species is producing endometrial infection. Here again, the Gram stain will be helpful. Mixed cultures usually are associated with smears showing clumps of bacteria and exfoliated epithelial cells. In the absence of Neisseria gonorrhoeae, such specimens which culture more than one aerobic or anaerobic bacterial species should be reported as mixed. When leukocytes, bacteria, and minimum numbers of epithelial cells are seen, as many as three aerobic and/or anaerobic species should be reported. If more species are isolated, a report of mixed culture should be provided. Anaerobic Infections Clinicians and microbiologists are becoming increasingly concerned with anaerobic infection. Technics for the iso-

6 872 BARTLETT A.J.C.P. Vol. 61 lation and identification of fastidious anaerobes have advanced at a more rapid rate than the development of clinical criteria for rational use of the information which is produced. Although anaerobic infection is an important problem which requires careful clinical and laboratory investigation, most specimens which are collected contain substantial amounts of indigenous oropharyngeal, cutaneous, or intestinal flora, much of which is anaerobic. Routine application of sensitive anaerobic technic to such specimens yields a potpourri of aerobic and anaerobic bacteria which have so increased demands on laboratory resources that many have estimated the cost to be at least double that for routine aerobic culture. Unless direct anaerobic bacteriology is applied selectively to specimens which have been collected by technics which specifically exclude contaminating indigenous anaerobic bacteria, laboratories will incur a new wave of increasing cost from this source. Controversy exists over the significance of isolation of anaerobes from urine. Until this is resolved, routine anaerobic culture of urine is not indicated. In selected situations where aerobic cultures fail to reveal pathogens in patients with clear signs of urinary tract infection, urine collected by suprapubic puncture can be usefully subjected to direct anaerobic culture. Discussion Most of these considerations are acknowledged by perceptive clinicians and microbiologists. Unfortunately, the pressure of other responsibilities contributes to a reluctance to follow through in assuring proper collection and submission of specimens, as well as processing and reporting which is relevant to clinical problems. The result is production of a substantial amount of useless information at considerable cost. Although educational efforts to reinforce recognition of these principles should be continued, it is doubtful that the problem will be resolved without development of stricter controls by clinical laboratories. As the current wave of austerity tightens constraints on hospital budgets, laboratory directors will be hard pressed to increase productivity without sacrificing quality. If medical staffs are clearly apprised of the need and means for establishing such controls, we believe that clinical laboratories can restrict processing and reporting to high quality material and simultaneously report information of greater clinical value. Our health care system cannot afford to allow microbiologists and laboratory workers to be pushed, or be allowed to drift, into the performance of clinically unnecessary and irrelevant work. References 1. Bailey WR, Scott EG: Haemophilus parainfluenzas and Haemophilus parahaemolyticus, Diagnostic Microbiology, St. Louis, C.V. Mosby, Barnett RN: Conference on the medical usefulness of microbiology. Am J Clin Pathol 54: , Belliveau RR: Normal vs pathogenic flora in acute pharyngitis. N Engl J Med 288, 797, Bodily HL, Updyke EL, Mason JO: H. parahaemolyticus, Diagnostic Procedures for Bacterial, Mycotic and Parasitic Infections. New York Am Pub Health Assoc 1970, p Breed RS, Murray EGD, Smith NR: Haemophilus parahaemolyticus, Bergey's Manual of Determinative Bacteriology, 7th Edition, Baltimore Williams and Wilkins, 1957, p Frankel S, Reitman S, Sonnenwirth AC: Gradwohl's Clinical Laboratory Methods and Diagnosis. Seventh edition. St. Louis, C.V. Mosby, vol 2, 1970, p Griner PF, Liptzin BL: Use of the laboratory in a teaching hospital, Implications for patient care, education and hospital costs. Ann Intern Med 75: , Kass EH: Asymptomatic infections of the urinary tract, Trans Assoc Am Physicians 69:56, Pittman M: A classification of the hemolytic bacteria of the genus Haemophilus: Haemophilus haemolyticus Bergey et al. and Haemophilus para haemolyticus nov. spec. J Bacterid 65: , 1953