Clinical use of rifampicin during routine reporting of rifampicin susceptibilities: a lesson in selective reporting of antimicrobial susceptibility data.

Increased use of rifampicin for in-patients was noted after the laboratory began reporting rifampicin susceptibilities routinely for all Gram-positive bacterial isolates. The appropriateness of rifampicin use was evaluated by chart review for in-patients administered rifampicin during two time periods, before and during routine rifampicin susceptibility reporting, respectively. While rifampicin susceptibility was reported routinely, four patients were subjected to potentially harmful misuse of rifampicin. These findings reconfirm the necessity of interdepartmental consultation and extensive staff education whenever a modification of antimicrobial susceptibility profile reporting is contemplated. Furthermore, they underscore the role of the clinical microbiology laboratory in guiding antimicrobial therapy through limited reporting of susceptibility data.

Isolator component responsible for inhibition of Mycobacterium avium-M. intracellulare in BACTEC 12B medium.

We previously reported an inhibitory effect on Mycobacterium avium-M. intracellulare (MAI) when blood collected and processed with the Isolator system was placed in BACTEC 12B bottles for radiometric monitoring. We sought to identify the specific component(s) of the Isolator lysis-anticoagulant reagent (LAR) responsible for the inhibitory effect. We added the three components of the LAR, saponin, polyanetholesulfonate, and polypropylene glycol (PPG), to triplicate sets of BACTEC bottles separately and in various combinations. These bottles were then seeded with 10(2) CFU of MAI. The growth index (GI) was observed over a 42-day period and was compared with the GI for a growth control bottle set with no reagents and with the GI for a bottle set containing an equivalent volume of LAR. Growth in all growth control bottles and those bottles containing no PPG reached the maximum GI (GI = 999) within 8 to 10 days. Growth in bottles containing PPG never reached the maximum GI before day 14. In addition, the GIs of one bottle containing all three reagent components as well as all of the bottles containing actual Isolator LAR failed to reach the maximum within 42 days. Our data suggest that PPG is the main cause of the inhibitory effect, but that a secondary synergistic interaction between all three of the reagents may also be present.

Performance of fungal blood cultures by using the Isolator collection system: is it cost-effective?

Enhanced recovery of fungal isolates from blood by using the Isolator system has been reported previously. We examined bacterial and fungal blood cultures during a 14-month period to determine if this enhanced recovery required a separate fungal culture and to determine the differential utility between a fungal blood culture and a routine bacterial culture. During this period, 84 of 5,196 (1.6%) fungal blood cultures and 170 of 25,702 (0.6%) bacterial blood cultures were positive for yeast or filamentous fungi. Thirty-seven positive fungal cultures, simultaneously collected, had correspondingly positive bacterial cultures. An additional 15 positive fungal cultures yielded isolates that had either been previously recovered from a bacterial culture or were recovered from a bacterial culture collected within 48 h. Of the 32 unpaired fungal cultures remaining, 5 were Candida albicans whose unique isolation was believed to be the result of specimen sampling variance rather than any enhanced recovery characteristics of fungal culture methods. Examination of patient data relating to the 27 remaining isolates (24 patients episodes) showed that only five fungal blood cultures (0.096% of all collected) had any impact on patient therapy decisions, and one of these was judged to be the cause of unnecessary therapy. Our data suggest that separate fungal cultures of blood are not cost-effective for those laboratories using the Isolator for routine blood cultures and furthermore may not be cost-effective for laboratories using automated broth systems that are comparable to the Isolator in recovery of fungi.

An evaluation of the necessity of 24-hour incubation for oxacillin minimum inhibitory concentrations.

Current standards of the National Committee for Clinical Laboratory Standards (NCCLS) for microtube dilution recommend 24-hour incubation of staphylococci when testing for oxacillin/methicillin resistance. This study was conducted to quantify the need for this requirement. Standard 16-hour readings were compared with subsequent 24-hour readings of 515 fresh clinical isolates (256 Staphylococcus aureus, 259 coagulase-negative staphylococci) that were susceptible to oxacillin (microtube dilution minimum inhibitory concentration [MIC] < or equal to 2 micrograms/mL) after 16 hours. Five hundred two of the susceptible isolates (97.5%) were still susceptible at 24 hours. The remaining 13 isolates were resistant (MIC > 2 micrograms/mL) at 24 hours. Duplicate retesting, alternative method testing (Kirby-Bauer, E-Test) and mec A gene analysis were performed on these 13 isolates. All 13 isolates possessed the mec A gene. Four isolates always tested resistant (including all 16-hour repeat microtube dilution readings), and one isolate always tested susceptible. The remaining eight isolates produced variable results suggestive of an MIC very close to the resistance/susceptible break point. Overall , conversion from susceptible to resistant was entirely dependent upon the 16-hour MIC. There were 53 isolates with 16-hour MICS of 2 micrograms/mL. All 13 converters came from this group. No isolate with an oxacillin MIC < 2 micrograms/mL at 16 hours was resistant at 24 hours. Based on these results, the authors instituted a selective reincubation of only those staphylococcal isolates with oxacillin readings of 2 micrograms/mL at 16 hours.

Tracking laboratory contamination by using a Bacillus cereus pseudoepidemic as an example.

From 1 March to 31 May 1990, Bacillus cereus was recovered from 24 of 5,534 (0.49%) blood cultures and 22 of 1,088 (2.02%) other body fluid cultures. The rarity of this organism as a pathogen and comparison with previous baseline rates led to the conclusion that it was a pseudoepidemic involving some form of culture contamination. Generalized precautions taken without specific knowledge of the contaminant source reduced the recovery rate of the organism. Recovery rates for the organism returned to normal baseline prevalence after environmental cultures and epidemiological analysis led to the sterilization of a contaminated water bath used for boiling thioglycollate media. The problems encountered in this investigation are examined, and a systematic approach to clinical laboratory epidemiology is outlined.

Captopril enhances in vitro human lymphocyte thymidine incorporation.

Angiotensin-converting enzyme activity is present in human sarcoid as well as murine schistosome granulomas. Inhibition of angiotensin-converting enzyme by captopril results in decreased granuloma size in animals. Since captopril is used clinically to treat hypertension, its effect on human lymphocyte thymidine incorporation was determined. It was found that 5 X 10(-5) M and 10(-4) M captopril enhances lymphocyte thymidine uptake induced by 25 micrograms/ml phytohaemagglutinin-P. This suggests that captopril can alter immunological reactivity in man and that angiotensin-converting enzyme may have an immunological function.

Neuropsychological performance one week after carotid endarterectomy reflects intra-operative ischemia.

Fourteen patients with severe bilateral carotid artery stenosis underwent carotid endarterectomy. Intra-operative ischemia was monitored by somatosensory evoked potentials (SSEP) bilaterally. Neuropsychological evaluations were completed within two days before operation and 4-9 days after operation. Complete loss of N1-P1 or P1-N2 components of the SSEP (seen in 4 patients) was associated with a worsening of neuropsychological abilities (p less than .01). Two of these patients subsequently had strokes (7 and 35 days after operation). No other patients in the series have had strokes. Patients whose N1-P1 or P1-N2 amplitudes decreased by 50% or more performed worse after operation than patients with less severe reductions in these amplitudes (p less than .02). Time since first ischemic symptoms, age, education, clamp time, pre-operative stroke, and interval from surgery to assessment were not statistically related to changes in neuropsychological abilities. Patients with ischemic events in the week prior to surgery tended to improve in neuropsychological abilities 4-9 days after operation (p less than .05). Recentness of ischemic episode, however, was not related to intra-operative SSEP change. Results suggest the potential utility of intra-operative SSEP monitoring and early post-operative neuropsychological assessments both for clinical and research purposes.

Long-latency somatosensory evoked potentials during carotid endarterectomy.

Scalp recorded somatosensory evoked cortical responses (SSEP) may be measured under general anesthesia to assess the electrical responsiveness of the brain. Such potentials were measured in 25 patients undergoing carotid endarterectomy without shunt. Electrical unresponsiveness occurred bilaterally in one patient and unilaterally in one patient. The patient with unilateral electrical silence developed a perioperative stroke, the only stroke in this series. Analysis of the SSEPs recorded from these patients suggests that profound ischemia produces electrical silence: that intermediate degrees of ischemia produce prolonged interpeak latencies and decreasing amplitudes in the SSEP. This modality seems to offer promise as an intraoperative monitor during cerebrovascular surgery.

Cognitive improvement after extracranial reconstruction for the low flow--endangered brain.

Twelve patients with multiple occlusive neck vessel lesions were thought to possess low flow-endangered brains. These patients were studied before and after carotid reconstruction with a battery of neuropsychologic tests emphasizing memory and mental agility. A closely matched control group was selected from patients undergoing endarterectomy for hemodynamically insignificant lesions. The patients with low flow-endangered brains showed significantly greater improvements in memory and mental abilities than did the control group. Reconstruction of neck vessels may reverse such global neurologic deficits in carefully selected patients.

Extended treatment with antithymocyte globulin (ATGAM) in renal allograft recipients.

Twenty renal allograft recipients were treated with antithymocyte globulin (ATGAM; ATG) for up to 16 weeks in addition to azathioprine and prednisone, while 20 controls received no ATG. The ATG group showed a lower incidence of first rejection episodes during the first month after transplantation, and also a better functional graft survival rate up to 2 years after transplantation. The results in this early ATG trial were better than those in subsequent trials which used 14-day treatment regimens. Longer treatment deserves another look.

Antithymocyte globulin (ATGAM) in renal allograft recipients. Multicenter trials using a 14-dose regimen.

Antithymocyte globulin (ATG, ATGAM; The Upjohn Company) was tested for efficacy and safety in controlled studies in 358 renal allograft recipients. A total of 183 patients were treated according to protocols prescribing 14 daily doses of ATG in addition to standard immunosuppressive therapy with azathioprine and prednisone, while 175 controls received no ATG. Four ATG lots were tested; results with each lot were analyzed separately, and the data were also pooled to obtain an overall impression. ATG delayed the onset of the first rejection episode during the prescribed treatment period (2 weeks). Concurrently, less i.v. steroid was required, but the steroid dosage requirement then rebounded in the 2 weeks after the end of the prescribed treatment period. ATG did not significantly improve the proportion of patients alive with functioning grafts 6 months after transplant, except with one of the four lots.

Neurotransmitter precursor amino acids in the treatment of multi-infarct dementia and Alzheimer's disease.

Ten patients with severe dementia due to Alzheimer's disease (AD) or multi-infarct dementia (MID) or both, were treated with the precursor amino acids of the neurotransmitters serotonin and dopamine. The precursor amino acids (PAA) were given orally in a preparation that included tyrosine (4 gm daily) and 5-hydroxy-tryptophan (5-HTP) (800 mg daily), plus carbidopa (100 mg daily) as an aromatic amino-acid decarboxylase inhibitor. Diagnosis was established by an electroencephalogram, brain scan, computerized axial tomographic scan, and in one case by necropsy findings. Serial clinical evaluations and measurements of neuropsychologic function were performed. Levels of homovanillic acid (HVA) and 5-hydroxyindole-acetic acid (5-HIAA) were determined before and after administration of probenecid. Side effects of the PAA therapy were diarrhea, drowsiness, nausea, vomiting and agitation, all of which were controlled by reducing the dosage. One patient with MID and one with AD+MID showed clinical and psychologic improvement, but the others did not improve. Analysis of the cerebrospinal fluid for HVA and 5-HIAA before and after the probenecid test indicated some improvement in the metabolic turnover of these acid metabolites of serotonin and dopamine after administration of their precursor amino acids.