Ron B. Schifman

Persistent Campylobacter jejuni Infections in Patients Infected with Human Immunodeficiency Virus (HIV)

We identified Campylobacter jejuni infections in four patients infected with the human immunodeficiency virus (HIV); three had persistent and severe C. jejuni infections. Multiple isolates obtained from each patient had the same biochemical and serotypic characteristics, indicating recurrent infection rather than reinfection with unrelated strains. Serum antibody responses to C. jejuni group antigens by enzyme-linked immunosorbent assay were markedly impaired in the three patients with persistent infection compared with forty-two immunocompetent C. jejuni-infected controls and with the HIV-infected patient who readily cleared the organism. One patient was bacteremic; his blood isolate was killed by normal serum but was resistant to his own serum, whereas a simultaneous stool isolate of a different serotype was sensitive. Failure of two patients to eradicate the organism and long-term administration of erythromycin therapy led to the in-vivo development of resistance to this antibiotic, which is most frequently used to treat C. jejuni infections.

Q-tracks: A College of American Pathologists program of continuous laboratory monitoring and longitudinal performance tracking

CONTEXT Continuous monitoring of key laboratory indicators of quality by hundreds of laboratories in a standardized measurement program affords an opportunity to document the influence of longitudinal tracking on performance improvement by participants focused on that outcome. OBJECTIVE To describe the results of the first 2 years of participation in a unique continuous performance assessment program for pathology and laboratory medicine. DESIGN Participants in any of 6 modules in the 1999 and 2000 College of American Pathologists (CAP) Q-Tracks program collected data according to defined methods and sampling intervals on standardized input forms. Data were submitted quarterly to CAP for statistical analysis. Interinstitutional comparison reports returned in 6 weeks provided each laboratory with its performance profile of key indicators and its percentile ranking compared with all participants in that quarter. This also included longitudinal comparisons of performance during previous cumulative quarters. Control charts graphically displayed data with flags identifying performance points that were out of statistical control. SETTING Hospital-based laboratories in the United States (98%), Canada, and Australia. PARTICIPANTS Voluntary subscriber laboratories in the CAP Q-Tracks performance measurement program: roughly 70% from hospitals of 300 occupied beds or fewer, 65% from private, nonprofit institutions, slightly more than half located in cities, one third from teaching hospitals, and 20% with pathology residency training programs. MAIN OUTCOME MEASURES Each module measured several major and additional minor quality indicators and unbenchmarked individualized data for internal use. RESULTS Participants in 4 of 6 Q-Tracks continuous monitors demonstrated statistically significant performance improvement trends in 1999 and 2000, which were most marked for laboratories that continued participation throughout both years. These monitors were wristband patient identification, laboratory specimen acceptability, blood product wastage, and intraoperative frozen section consultation. CONCLUSIONS Key continuous indicators chosen on the basis of a decades experience in the CAP Q-Probes quality improvement program are useful measurement and benchmarking tools for laboratories to improve performance. In general, measures in which there is a broad range of demonstrable performance initially are most optimal for subsequent improvement using continuous monitoring. These studies have shown that quality is not static, but rather is a moving benchmark of performance as seen in the redefinition of benchmarks over time by participants in the first 2 years of the CAP Q-Tracks program.

Prospective Comparison between Serum Monoclonal Prostate Specific Antigen and Acid Phosphatase Measurements in Metastatic Prostatic Cancer

Prostate specific antigen, prostatic acid phosphatase antigen and acid phosphatase activity were measured on 175 serum samples serially collected from 80 patients with metastatic stage D adenocarcinoma of the prostate. Prostate specific antigen and prostatic acid phosphatase antigen concentrations were measured with a monoclonal radioimmunometric assay, and acid phosphatase activity was measured enzymatically. The over-all frequency of abnormal levels of prostate specific antigen (76 per cent) was significantly greater than abnormal prostatic acid phosphatase antigen (60 per cent) and acid phosphatase activity (49 per cent) results (p less than 0.001). These differences were greater among the subset of patients in clinical remission. Levels greater than 10 times normal were observed in 68 per cent of prostate specific antigen, 43 per cent of prostatic acid phosphatase antigen and 31 per cent of acid phosphatase activity measurements (p less than 0.001). Three or more serial prostate specific antigen measurements in 17 patients demonstrated excellent correlation with independently assessed clinical disease activity. These results suggest that prostate specific antigen is a more sensitive and potentially more useful tumor marker than acid phosphatase measurements in patients with metastatic prostatic carcinoma.

Fungemia due to Coccidioides immitis. An analysis of 16 episodes in 15 patients and a review of the literature.

Sixteen episodes of fungemia due to Coccidioides immitis were identified in 15 patients over a 7-year period at 2 hospital associated with the University of Arizona in Tucson. Fourteen of the 15 patients were male and 13 had an underlying condition, including malignancy in 6 and AIDS in 3. Ten of the patients were receiving corticosteroids at the time of fungemia. TP antibodies were present in 5 of 9 episodes and some titer of CF antibody was present in 7 of 11 instances. None of the 10 patients tested had a positive 1:100 coccidioidin skin test. In 11 of 15 episodes, a miliary chest roentgenographic pattern was apparent at the time of fungemia. Eleven of the 16 episodes ended in death within 1 month of the positive blood culture. Fungemic patients were compared to patients with culture-proven coccidioidomycosis without fungemia and differed from them significantly in 3 respects. First, fungemic patients were more likely to have a diffuse miliary pattern on chest radiograph. Second, all fungemic patients had, by definition, disseminated coccidioidomycosis and this was more likely among fungemic patients than among non-fungemic patients. Finally, fungemic patients were more likely to die within 1 month of the positive culture for C. immitis. Fungemia occurred in greater than 30% of patients with culture-proven coccidioidomycosis who had a blood culture performed. These results suggest that coccidioidal fungemia is a marker for a severe, acute form of disseminated coccidioidomycosis associated with a high mortality.

Comparison of MRSASelect Agar, CHROMagar Methicillin-Resistant Staphylococcus aureus (MRSA) Medium, and Xpert MRSA PCR for Detection of MRSA in Nares: Diagnostic Accuracy for Surveillance Samples with Various Bacterial Densities

ABSTRACT Rapid laboratory methods provide optimal support for active surveillance efforts to screen for methicillin-resistant Staphylococcus aureus (MRSA). Most laboratories struggle to determine the optimal use of resources, considering options to balance cost, speed, and diagnostic accuracy. To assess the performance of common methods, the first comparison of MRSASelect agar (MS) and CHROMagar MRSA (CA), with and without broth enrichment followed by a 24-h subculture to MS, was performed. Results were compared to those of the Xpert MRSA assay. For direct culture methods, the agreement between MS and CA was 98.8%. At 18 h, direct MS identified 93% of all positive samples from direct culture and 84% of those identified by the Xpert MRSA. For Trypticase soy broth-enriched MS culture, incubated overnight and then subcultured for an additional 24 h, the agreement with Xpert MRSA was 96%. The agreement between direct MS and Xpert MRSA was 100% when semiquantitative culture revealed a bacterial density of 2+ or greater; however, discrepancies between culture and Xpert MRSA arose for MRSA bacterial densities of 1+ or less, indicating low density as a common cause of false-negative culture results. Since 1+ or less was established as the most common MRSA carrier state, broth enrichment or PCR may be critical for the identification of all MRSA carriers who may be reservoirs for transmission. In this active-surveillance convenience sample, the use of broth enrichment followed by subculture to MS offered a low-cost but sensitive method for MRSA screening, with performance similar to that of Xpert MRSA PCR.

Intracellular adenosine triphosphate as a measure of human tumor cell viability and drug modulated growth.

SummaryAdenosine triphosphate is the primary energy unit for cells, and levels of this compound offer a potential marker for cell viability and growth. The availability of a bioluminescence assay allows for a rapid, sensitive, and reproducible measurement of ATP. A method is described for the quantification of intracellular ATP levels in human cancer cells. ATP levels were linearly related to the number of viable cells and increased with time in human cancer cell line cultures correlating with growth kinetics. The effect of 5-fluorouracil, doxorubicin, methotrexate, cytosine arabinoside, nitrogen mustard, melphalan, vinblastine, and cisplatin on the growth of human cancer cell lines was studied utilizing ATP levels. ATP levels and colony formation in agar of drug-exposed cells were compared. Overall there was a significant correlation between drug effects on colony formation and ATP levels. The ATP assay is rapid, simple, reproducible, and a relatively inexpensive method of quantifying drug effects on malignant cells. This makes it a potentially useful method for screening new anticancer drugs in human cancer cell lines.

Red blood cell zinc protoporphyrin testing for iron-deficiency anemia in pregnancy

The diagnostic value of ferritin, transferrin saturation, and red blood cell zinc protoporphyrin for detecting iron depletion and predicting third-trimester anemia was studied in 87 women attending a private obstetrics clinic. A decline in ferritin and transferrin saturation and an increase in red blood cell zinc protoporphyrin levels were observed in third-trimester measurements when compared with those of the first trimester. Third-trimester anemia (hemoglobin less than 11.5 gm/dl or 115 gm/L) was detected in 13 (15%) women. Red blood cell zinc protoporphyrin was the only test that consistently demonstrated significantly different mean values between anemic and normal subgroups. The diagnostic sensitivity and predictive value of red blood cell zinc protoporphyrin for evaluating iron depletion and risk of anemia in pregnancy compared favorably to those of ferritin and transferrin saturation measurements. The operational simplicity and low cost of red blood cell zinc protoporphyrin measurements are additional characteristics that favor this procedure for office testing.

Solitary Blood Cultures as a Quality Assurance Indicator

For patients with suspected bacteremia, at least two separate blood cultures are recommended to achieve maximum sensitivity and to properly interpret re sults. Since a single blood collection may signify an improper procedure with serious consequences if the diagnosis of blood stream infection is missed, we in vestigated this problem with studies at three teaching hospitals (A, B, and C) and by a survey of 38 other hospitals. The incidence of solitary blood cultures ranged from 1 to 99% (median 26%) at the surveyed institutions. Among the cases investigated at hospitals B and C, between 10 and 30% of solitary blood cul tures were not clinically indicated, while most of the others were caused by the physician not knowing that one culture was insufficient or by failure to complete the diagnostic plan. Focused concurrent intervention at hospital B was associated with reductions in soli tary blood cultures from 40.0 to 24.6% (p = 0.045) and a decline in those not indicated from 38.1 to 12.5% (p = 0.192). Global educational efforts at hos pital A were associated with a decrease in solitary blood culture rates from 52 to 37% (p = 0.016). These results show that blood culture practice varies widely among institutions in spite of consensus recommen dations for proper specimen collections. We estimate that, nationwide, up to 18,000 etiologic diagnoses of bacteremia are missed annually because of this prob lem. Monitoring institutional solitary blood cultures is recommended as a test utilization indicator and as the basis for improving blood culture practice.

Point-of-Care Glucose Critical Values: A Q-Probes Study Involving 50 Health Care Facilities and 2349 Critical Results.

CONTEXT Accuracy of blood glucose measurements in the critical value range is important for properly treating patients with severe hypoglycemia and hyperglycemia. OBJECTIVE To evaluate the performance and reliability of point-of-care glucose (POCG) results in the critical value range among multiple facilities. DESIGN Q-Probes participants retrospectively collected data from up to 50 POCG results in their critical value range including patient location, type of testing operator, repeat glucose results, and caregiver notification. A repeat measurement at 10 minutes or less that was within 15 mg/dL of initial critical low or 20% of initial critical high value was considered a confirmed result. RESULTS Fifty facilities submitted data. Of 2349 critical POCG measurements, 1386 (59.0%) were retested. The median institutional retest rate was 56%. The retest rate was significantly higher when initial results were in the critical low range, P < .001. Although 30 of 50 facilities (60%) had written procedures for retesting, this was not associated with higher retest rates (P = .34). Among 35 facilities that routinely retested critical POCG results, 23 (65.7%) had criteria defined for interpreting results. The median institutional confirmation rate for retested specimens was 81.7%. The median institutional rate for caregiver notification of critical POCG results was 85.7%. Five hundred eighty-six of 1488 critical POCG notifications (39.4%) were done on patients in whom specimens were not retested. CONCLUSIONS This study shows that POCG results in the critical range may be unreliable because of testing errors that are not recognized from lack of confirmatory testing. In addition, notification of critical POCG results is not consistently performed.

Reliability of point-of-care capillary blood glucose measurements in the critical value range.

CONTEXT Point-of-care glucose (POCG) testing on capillary blood specimens is central to maintaining glycemic control in patients with diabetes. Although there are known performance issues with POCG methods, especially for maintaining tight glucose control, there is little information about the accuracy of results in the critical ranges that may involve life-threatening conditions. OBJECTIVES To evaluate the reliability of POCG measurements in critical, high (>600 mg/dL) and low (<40 mg/dL) ranges. DESIGN One-year retrospective analysis of POCG (ACCU-CHEK glucose meter, Roche Diagnostics Corporation, Indianapolis, Indiana) results for routine patient care were obtained. The frequency and accuracy of repeat testing after critical POCG results was analyzed. A convenience sample of noncritical capillary POCG measurements retested on venous blood specimens by another point-of-care device (RAPIDPoint 405 analyzer, Siemens Medical Solutions USA, Malvern, Pennsylvania) was also evaluated. RESULTS Critical values were observed in 2.4 per 1000 POCG tests (256 of 105,928; 0.24%), with the highest rate (76 of 2289; 3.32%) from the emergency department. Twice as many critical high values as critical low values were seen. Nearly 80% of critical POCG tests (204 of 256) were repeated within 10 minutes. Of these 204 repeat measurements, 112 (54.9%) met accuracy criteria (±15 mg/dL of low and ±20% of high initial values). Accuracy was significantly higher when retesting was performed on the same meter or by the same operator (P ≤ .05). Comparison of capillary and venous POCG testing of noncritical results showed no significant difference (P = .95), with 89.8% (125 of 139) meeting accuracy criteria. CONCLUSIONS POCG measurements in the critical range are frequently erroneous, which is likely caused by preanalytic factors associated with sampling capillary blood. POCG testing practices should include retesting to confirm critical results.