Charles E. Stager

Effects of Requiring Prior Authorization for Selected Antimicrobials: Expenditures, Susceptibilities, and Clinical Outcomes

Antimicrobial control programs are widely used to decrease drug expenditures, but effects on antimicrobial resistance and outcomes for patients are unknown. When a requirement for prior authorization for selected parenteral antimicrobial agents was initiated at our urban, county teaching hospital, total parenteral antimicrobial expenditures decreased by 32%. Susceptibilities to all beta-lactam and quinolone antibiotics increased, with dramatic increased susceptibilities in isolates recovered in intensive care units, increased susceptibilities in isolates recovered in other inpatient sites, and little change in susceptibilities in isolates recovered in outpatient sites despite no change in infection control practices. For patients with bacteremia due to gram-negative organisms, overall survival did not change with restrictions. No differences occurred in the median time from initial positive blood culture to receipt of an appropriate antibiotic or in the median time from positive blood culture to discharge from the hospital. Thus, requiring preapproval for selected parenteral agents can decrease antimicrobial expenditures and improve susceptibilities to antibiotics without compromising patient outcomes or length of hospital stay.

Molecular Genetic Analysis of Nucleotide Polymorphisms Associated with Ethambutol Resistance in Human Isolates of Mycobacterium tuberculosis

ABSTRACT Ethambutol (EMB) is a central component of drug regimens used worldwide for the treatment of tuberculosis. To gain insight into the molecular genetic basis of EMB resistance, approximately 2 Mb of five chromosomal regions with 12 genes in 75 epidemiologically unassociated EMB-resistant and 33 EMB-susceptible Mycobacterium tuberculosis strains isolated from human patients were sequenced. Seventy-six percent of EMB-resistant organisms had an amino acid replacement or other molecular change not found in EMB-susceptible strains. Thirty-eight (51%) EMB-resistant isolates had a resistance-associated mutation in only 1 of the 12 genes sequenced. Nineteen EMB-resistant isolates had resistance-associated nucleotide changes that conferred amino acid replacements or upstream potential regulatory region mutations in two or more genes. Most isolates (68%) with resistance-associated mutations in a single gene had nucleotide changes in embB, a gene encoding an arabinosyltransferase involved in cell wall biosynthesis. The majority of these mutations resulted in amino acid replacements at position 306 or 406 of EmbB. Resistance-associated mutations were also identified in several genes recently shown to be upregulated in response to exposure of M. tuberculosis to EMB in vitro, including genes in theiniA operon. Approximately one-fourth of the organisms studied lacked mutations inferred to participate in EMB resistance, a result indicating that one or more genes that mediate resistance to this drug remain to be discovered. Taken together, the results indicate that there are multiple molecular pathways to the EMB resistance phenotype.

Automated systems for identification of microorganisms.

Automated instruments for the identification of microorganisms were introduced into clinical microbiology laboratories in the 1970s. During the past two decades, the capabilities and performance characteristics of automated identification systems have steadily progressed and improved. This article explores the development of the various automated identification systems available in the United States and reviews their performance for identification of microorganisms. Observations regarding deficiencies and suggested improvements for these systems are provided.

Rapid Detection of Microorganisms in Blood Cultures of Newborn Infants Utilizing an Automated Blood Culture System

Background. Neonatal sepsis is a low incidence, high-risk disease with many sepsis work-ups performed to detect a single case. Seventy-two hours of antibiotic therapy have been traditionally recommended pending negative culture results. Improved culture media and new technology integrated into blood culture systems could shorten incubation time required to detect positive culture results. This would then change the length of antibiotic therapy in the management of the newborn infant with suspected sepsis. In addition, previous data supporting the 72-hour recommendation were retrospectively acquired, utilized nonautomated systems, and reported in an era with a different population of microorganisms cultured in special care nurseries. Objective. Evaluate the time of incubation to detect positive blood cultures from newborn infants with suspected sepsis using a computer-assisted, automated blood culture system, ESP (Trek Diagnostic Systems, Inc, Westlake, OH). Design. Prospective, observational study. Patients and Setting. All positive blood culture results that were obtained from term and preterm newborn infants born from November 1993 through June 1997 at a publicly funded hospital with over 6000 live births per year. Methods. As positive blood culture results were identified, data were prospectively obtained from the patients medical record. The computer algorithm in the automated blood culture system determined the time to positivity. Time to positivity was determined for blood cultures obtained before the initiation antimicrobial therapy and compared with those cultures obtained after beginning therapy. Time to positivity was also evaluated for clinically important Gram-positive and Gram-negative bacteria and yeast. Results. Four hundred fifty-five positive blood culture results were obtained from 222 patients. Gram-positive organisms accounted for 80% (366/455) of the positive culture results, Gram-negative organisms accounted for 11% (48/455), and yeast for 9% (41/455). Virtually all cultures growing clinically significant Gram-positive and Gram-negative organisms were positive by 24 to 36 hours of incubation. Cultures growing Staphylococcus epidermidis were virtually all positive after 36 to 48 hours of incubation. Of cultures growing yeast, 88% (36/41) were positive by 48 hours of incubation. There was no difference in time to positivity in pretherapy or posttherpay obtained positive blood cultures. Prenatally administered antibiotics did not affect time to positivity in positive cultures drawn on the first day of life. In a selected group of microorganisms that are the frequent cause of bacteremia in term infants, 97% and 99% of cultures were positive by 24 to 36 hours of incubation when only pretherapy cultures are evaluated. Conclusions. The ESP blood culture system identified 77%, 89% and 94% of all microorganisms at 24, 36, and 48 hours of incubation in aerobic cultures obtained from both term and preterm infants. Introduction of antimicrobial therapy did not affect time to positivity. Reducing duration of antibiotic therapy to 24 to 36 hours should be considered in term, asymptomatic newborn infants undergoing evaluation for suspected sepsis for maternal indications. Confirmation of similar rapidity of detection using other blood culture systems should be undertaken.

Identification of Methicillin-Resistant or Methicillin-Susceptible Staphylococcus aureus in Blood Cultures and Wound Swabs by GeneXpert

Until a decade ago, clinicians could use epidemiological clues to select empirical therapy for methicillin-susceptible Staphylococcus aureus (MSSA) or methicillin-resistant S. aureus (MRSA) ([5][1]). The emergence of MRSA as a community pathogen and the documentation of the inferiority of non-beta-

Sequential Outbreaks of Infections by Distinct Acinetobacter baumannii Strains in a Public Teaching Hospital in Houston, Texas

ABSTRACT Invasive disease due to Acinetobacter baumannii is an increasing problem in health care settings worldwide. Whether certain clones of A. baumannii are more likely to cause invasive disease in hospitalized patients is unknown. We studied all patients at a public teaching hospital in Houston, Texas, from whom the Acinetobacter calcoaceticus-Acinetobacter baumannii complex was isolated over a 14-month period in 2005 to 2006. One hundred seven unique patient isolates were identified, with 87 of the strains classified as being A. baumannii, the majority of which were multidrug resistant. The A. baumannii isolates were comprised of 18 unique pulsed-field types, with strains of clone A and clone B accounting for 66 of the 87 isolates. Epidemiologic analysis showed the predominance of the two A. baumannii clones at distinct time periods, with the remainder of the A. baumannii and non-A. baumannii strains being evenly distributed. Patients from whom clone A strains were isolated were more likely to be bacteremic than were patients with other A. baumannii isolates. Conversely, clone B strains were more likely to be isolated from patients with tertiary peritonitis. Patients from whom clone A was isolated had a significantly higher rate of mortality. Multilocus sequence typing demonstrated that clones A and B are related to each other and to A. baumannii strains previously isolated in Western Europe, sharing five of seven alleles. Taken together, we conclude that the outbreak of the A. calcoaceticus-A. baumannii complex in our institution was due to two distinct A. baumannii clones that were associated with significantly different patient outcomes.

Intensity of Infection in AIDS-Related Intestinal Microsporidiosis

To quantify intensity of infection in AIDS-related microsporidiosis, 20 patients with known microsporidiosis submitted stools for quantitative spore counts after staining with a calcofluor white stain. Nine patients collected stools for 24 h, for assessment of daily spore excretion, stool-to-stool variation in spore excretion, and patient-to-patient variation in intensity of infection. The number of organisms seen in small bowel biopsy specimens from 7 patients was compared with quantitative fecal spore excretion. Fecal spore concentration in 20 patients ranged from 4.5x105 to 4.4x108 spores/mL of stool. There was a strong correlation between fecal spore excretion and duodenal biopsy spore counts (r=.82; P<.024). Microsporidium infections in AIDS patients can be quantified by counting spores in stool and by small bowel biopsy. Variations in intensity of infection from patient to patient are great and are similar to those in AIDS-related Cryptosporidium infection.

In Vitro Activity and Durability of a Combination of an Antibiofilm and an Antibiotic against Vascular Catheter Colonization

ABSTRACT Catheter-associated infections can cause severe complications and even death. Effective antimicrobial modification of catheters that can prevent device colonization has the potential of preventing clinical infection. We studied in vitro the antimicrobial activities of central venous catheters impregnated with N-acetylcysteine (NAC), an antibiofilm agent, and a broad-spectrum antibiotic against a range of important clinical pathogens. NAC-levofloxacin-impregnated (NACLEV) catheters were also evaluated for their antiadherence activity. NACLEV catheters produced the most active and durable antimicrobial effect against both Gram-positive and Gram-negative isolates and significantly reduced colonization (P < 0.0001) by all tested pathogens compared to control catheters. These in vitro results suggest that this antimicrobial combination can potentially be used to combat catheter colonization and catheter-associated infection.

Detection of Pneumocystis carinii in tracheal aspirates of intubated patients using calcofluor-white (Fungi-fluor®) and immunofluorescence antibody (Genetic Systems) stains

OBJECTIVE To compare the detection rate of Pneumocystis carinii in endotracheal aspirates with that rate in bronchoalveolar lavage fluid, using calcofluor-white (Fungi-Fluor) and immunofluorescence antibody (Genetic Systems) staining methods. DESIGN Prospective, consecutive cases. SETTING Medical intensive care unit at Ben Taub General Hospital. PATIENTS Thirty-one intubated patients admitted with respiratory failure and suspected P. carinii pneumonia. INTERVENTIONS An endotracheal aspirate specimen was obtained after maximally advancing a closed-system suction catheter, instilling aliquot portions of saline, and suctioning the lavage fluid. This procedure was followed within 30 mins by fiberoptic bronchoscopy and bronchoalveolar lavage. MEASUREMENTS AND MAIN RESULTS Endotracheal aspirate and bronchoalveolar lavage specimens from each patient were mixed with Saccomanos fixative, blended, and centrifuged. Using a modified method for P. carinii cysts, the sediment was stained with the test calcofluor-white stain Solution A and the test antibody stain. The test antibody stain on the bronchoalveolar lavage specimens was positive for P. carinii for 13 patients and was used as the standard for comparison. In the endotracheal aspirate specimens, the test antibody stain detected 12 (92%) P. carinii-positive patients while the test calcofluor-white stain detected ten (77%) P. carinii-positive patients. CONCLUSIONS We described a simple method for obtaining, processing, and staining endotracheal aspirate specimens for P. carinii. Obtaining an endotracheal aspirate specimen did not require specially trained personnel or a specialized and more expensive catheter, and was not associated with any complications.

Direct antimicrobial drug susceptibility testing of Mycobacterium tuberculosis by the radiometric method

Direct-drug-susceptibility tests were performed on clinical specimens positive for acid-fast bacilli by either Ziehl-Neelsen or fluorochrome staining. The results of conventional agar dilution (Vestal, 1975) and a modified radiometric (BACTEC) method were compared. A total of 580 smear-positive specimens were tested by the BACTEC method at three separate sites. Three hundred and seventy-seven of these were culture positive for M. tuberculosis, and 343 (91%) yielded acceptable direct-susceptibility-test results. We used the conventional method to determine that 343 of 519 smear-positive specimens were culture positive for M. tuberculosis, and 212 (62%) produced acceptable results within 3 wks. Conventional results were reported in 3-4 wks, while the time required to obtain results with the BACTEC method ranged from 5 to 21 days (average 11.5 days). Results indicate that the radiometric method provides reportable results more frequently with time savings as compared to the conventional method.