Opportunities to Enhance Diagnostic Testing and Antimicrobial Stewardship: A Qualitative Multinational Survey of Healthcare Professionals.

INTRODUCTION: Antimicrobial resistance (AMR) is a global public health challenge. Global efforts to decrease AMR through antimicrobial stewardship (AMS) initiatives include education and optimising the use of diagnostic technologies and antibiotics. Despite this, economic and societal challenges hinder AMS efforts. The objective of this study was to obtain insights from healthcare professionals (HCPs) on current challenges and identify opportunities for optimising diagnostic test utilisation and AMS efforts. METHODS: Three hundred HCPs from six countries (representing varied gross national incomes per capita, healthcare system structure, and AMR rates) were surveyed between November 2022 through January 2023. A targeted literature review and expert interviews were conducted to inform survey development. Descriptive statistics were used to summarise survey responses. RESULTS: These findings suggest that the greatest challenges to diagnostic test utilisation were economic in nature; many HCPs reported that AMS initiatives were lacking investment (32.3%) and resourcing (40.3%). High resistance rates were considered the greatest barriers to appropriate antimicrobial use (52.0%). Most HCPs found local and national guidelines to be very useful (≥ 51.0%), but areas for improvement were noted. The importance of AMS initiatives was confirmed; diagnostic practices were acknowledged to have a positive impact on decreasing AMR (70.3%) and improving patient outcomes (81.0%). CONCLUSION: AMS initiatives, including diagnostic technology utilisation, are pivotal to decreasing AMR rates. Interpretation of these survey results suggests that while HCPs consider diagnostic practices to be important in AMS efforts, several barriers to successful implementation still exist including patient/institutional costs, turnaround time of test results, resourcing, AMR burden, and education. While some barriers differ by country, these survey results highlight areas of opportunities in all countries for improved use of diagnostic technologies and broader AMS efforts, as perceived by HCPs. Greater investment, resourcing, education, and updated guidelines offer opportunities to further strengthen global AMS efforts.

Antimicrobials are medications used to treat infections caused by bacteria (e.g. antibiotics), viruses, parasites, and fungi. Over time, these microbes may become resistant to antimicrobials, limiting how well they work. This often happens as a result of overuse, using antimicrobials when there is not an infection, or using an inappropriate antimicrobial. Antimicrobial resistance is a growing global problem. Antimicrobial stewardship programs aim to improve appropriate use of antimicrobials. Diagnostic testing plays an important role in these programs by identifying the microbes responsible for infections so patients can be given the right treatment as quickly as possible. We aimed to obtain the perspective of healthcare professionals from six countries on the challenges of and ways to improve diagnostic testing and antimicrobial stewardship programs. We found that some of the greatest challenges were related to costs. Approximately one-third of participants said that antimicrobial stewardship initiatives were lacking investment (32.3%) and resourcing (40.3%). High rates of antimicrobial resistance were identified as the greatest barriers to appropriate antimicrobial use (52.0%). Participants said that diagnostic practices have a positive impact on decreasing antimicrobial resistance (70.3%) and improving patient outcomes (81.0%). Overall, we found that healthcare professionals consider diagnostic tests to be an important part of antimicrobial stewardship, but there are several barriers to their success, including patient/hospital costs, turnaround time of test results, resourcing, antimicrobial resistance, and education. To overcome these barriers, increased funding, education, and resourcing, regular guideline updates, and development of optimised testing algorithms may help to improve antimicrobial stewardship and ultimately decrease antimicrobial resistance.

Comparison of BACTEC PLUS blood culture media to BacT/Alert FA blood culture media for detection of bacterial pathogens in samples containing therapeutic levels of antibiotics.

Blood culture bottles with antimicrobial removal systems are recommended for patients who develop fever while on antibiotics. This study compared the ability of Becton Dickinson (Sparks, MD) BACTEC PLUS bottles and bioMerieux (Durham, NC) BacT/Alert FA bottles to effectively remove vancomycin, cefoxitin, ceftriaxone, cefepime, piperacillin-tazobactam, ampicillin, oxacillin, gentamicin, and a combination of gentamicin/penicillin, thus allowing bacterial pathogens to grow. Each bottle was spiked with 10 ml of human blood, antibiotic, and strains of organisms susceptible to the antibiotic evaluated. The organisms used were type strains and clinical isolates of Staphylococcus aureus (methicillin susceptible and resistant), Streptococcus pneumoniae, a viridans streptococcus, Enterococcus faecalis, Enterococcus faecium, Streptococcus agalactiae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Testing was completed in triplicate, using 10 to 100 CFU/ml of organisms with various concentrations of each antibiotic. Two rounds of testing were completed per antibiotic/organism combination. Bottles were mixed and loaded onto their respective instruments as per the manufacturer's instructions. Antimicrobial removal was evaluated on the basis of time to detection of organism growth, for up to 5 days of incubation. Overall, the BacT/Alert FA system recovered 25.1% of strains from test bottles and 96.9% of strains from growth control bottles (no antibiotic added), and the BACTEC PLUS system recovered 95.1% of strains from test bottles and 100% of strains from growth control bottles. Both systems performed well in the detection of Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa in the presence of gentamicin. In the presence of ceftriaxone, neither system was able to recover Streptococcus pneumoniae. The ability to remove vancomycin and cefoxitin was also determined by measuring antibiotic levels remaining in bottles after 1 h of incubation. The results demonstrated remaining levels of 72 to 90% of vancomycin and 71 to 72% of cefoxitin in the BacT/Alert system. For the BACTEC system, remaining levels were 0 to 30% of vancomycin and 0% of cefoxitin. Under these simulated conditions, the BACTEC PLUS system was superior to the BacT/Alert FA system in recovering gram-positive and gram-negative bacterial pathogens in the presence of beta-lactam antibiotics, gentamicin/penicillin, and vancomycin.

Evaluation of the BD Phoenix automated microbiology system for identification and antimicrobial susceptibility testing of Enterobacteriaceae.

We evaluated the accuracy of the BD Phoenix system for the identification (ID) and antimicrobial susceptibility testing (AST) of 251 isolates of the family Enterobacteriaceae representing 31 species. Organisms were inoculated onto the Phoenix panel according to the manufacturer's instructions. The results from conventional biochemical tests were used for the reference method for ID. Agar dilution, performed according to the CLSI guidelines, was the reference AST method. Essential and categorical agreements were determined. The overall levels of agreement for the genus- and species-level identifications were 95.6% and 94.4%, respectively. Fourteen isolates were incorrectly identified by the Phoenix system; 10 of these were incorrectly identified to the species level. Three of these were Enterobacter (Pantoea) species and four of these were Shigella spp. misidentified as Escherichia coli. For AST results, the essential and categorical agreements were 98.7% and 97.9%, respectively. The very major error, major error, and minor error rates were 0.38%, 0.33%, and 1.8%, respectively. Six isolates (three E. coli isolates and three Klebsiella isolates) were extended-spectrum beta-lactamase producers. All six were flagged by the Phoenix system expert rules. The Phoenix system compares favorably to traditional methods for ID and AST of Enterobacteriaceae.

Evaluation of the BD Phoenix automated microbiology system for identification and antimicrobial susceptibility testing of staphylococci and enterococci.

We evaluated the Phoenix automated microbiology system (BD Diagnostic Systems, Sparks, MD) for the identification (ID) and antimicrobial susceptibility testing (AST) of challenge and clinical staphylococci and enterococci recovered from patients in a tertiary-care medical center. In total, 424 isolates were tested: 90 enterococci; 232 Staphylococcus aureus isolates, including 14 vancomycin-intermediate S. aureus isolates; and 102 staphylococci other than S. aureus (non-S. aureus). The Phoenix panels were inoculated according to the manufacturer's instructions. The reference methods for ID comparisons were conventional biochemicals and cell wall fatty acid analysis with the Sherlock microbial identification system (v 3.1; MIDI, Inc. Newark, DE). Agar dilution was the reference AST method. The overall rates of agreement for identification to the genus and the species levels were 99.7% and 99.3%, respectively. All S. aureus isolates and enterococci were correctly identified by the Phoenix panels. For the non-S. aureus staphylococci, there was 98.0% agreement for the ID of 16 different species. The AST results were stratified by organism group. For S. aureus, the categorical agreement (CA) and essential agreement (EA) were 98.2% and 98.8%, respectively. Three of three very major errors (VMEs; 1.7%) were with oxacillin. For non-S. aureus staphylococci, the CA, EA, VME, major errors, and minor error rates were 95.7%, 96.8%, 0.7%, 1.7%, and 2.9%, respectively. The two VMEs were with oxacillin. For the enterococci, there was 100% CA and 99.3% EA. All 36 vancomycin-resistant enterococci were detected by the Phoenix system. The Phoenix system compares favorably to traditional methods for the ID and AST of staphylococci and enterococci.

Multicenter evaluation of BBL CHROMagar MRSA medium for direct detection of methicillin-resistant Staphylococcus aureus from surveillance cultures of the anterior nares.

Active surveillance for methicillin-resistant Staphylococcus aureus (MRSA) is among the strategies recommended by the Society for Healthcare Epidemiology of America for control of nosocomial MRSA infections. Infection control and laboratory personnel desire rapid, sensitive, and inexpensive methods to enhance surveillance activities. A multicenter study was performed to evaluate a new selective and differential chromogenic medium, BBL CHROMagar MRSA (C-MRSA) medium (BD Diagnostics, Sparks, MD), which enables recovery and concomitant identification of MRSA strains directly from nasal swab specimens taken from the anterior nares. Specimens were inoculated to C-MRSA and Trypticase soy agar with 5% sheep blood agar (TSA II, BD Diagnostics). Mauve colonies on C-MRSA at 24 h and 48 h and suspicious colonies on TSA II were confirmed as Staphylococcus aureus by Gram stain morphology and a coagulase test. In addition, the results of C-MRSA were compared to results of susceptibility testing (five different methods) of S. aureus strains isolated on TSA II. A total of 2,015 specimens were inoculated to C-MRSA and TSA II. Three hundred fifty-four S. aureus isolates were recovered; 208 (59%) were oxacillin (methicillin) susceptible and 146 (41%) were oxacillin resistant (MRSA). On C-MRSA, 139/146 or 95.2% of MRSA isolates were recovered, whereas recovery on TSA II was 86.9% (127/146) (P = 0.0027). The overall specificity of C-MRSA was 99.7%. When C-MRSA was compared to each susceptibility testing method, the sensitivity and specificity, respectively, were as follows: oxacillin MIC by broth microdilution, 94.4% and 96.7%; oxacillin screen agar, 94.3% and 96.7%; PBP2' latex agglutination, 93.7% and 98.5%; cefoxitin disk diffusion, 95.0% and 98.1%; and mecA PCR, 95.1% and 98.1%. In this study, C-MRSA was superior to TSA II for recovery of MRSA from surveillance specimens obtained from the anterior nares and was comparable to conventional, rapid, and molecular susceptibility methods for the identification of MRSA isolates.

Two-year evaluation of Borrelia burgdorferi culture and supplemental tests for definitive diagnosis of Lyme disease.

Lyme disease is usually diagnosed and treated based on clinical manifestations. However, laboratory testing is useful for patients with confusing presentations and for validation of disease in clinical studies. Although cultivation of Borrelia burgdorferi is definitive, prior investigations have shown that no single test is optimal for Lyme disease diagnosis. We applied high-volume blood culture, skin biopsy culture, PCR, and serodiagnosis to a cohort of patients with suspected Lyme disease acquired in Maryland and southern Pennsylvania. The study was performed to confirm the relative utility of culture and to identify laboratory testing algorithms that will supplement clinical diagnosis. Overall, 30 of 86 patients (35%) were culture positive, whereas an additional 15 of 84 (18%) were seropositive only (51% total sero- and culture positive), and PCR on skin biopsy identified 4 additional patients who were neither culture nor seropositive. Among 49 laboratory test-positive patients, the highest sensitivity (100%) for diagnosis was obtained when culture, skin PCR, and serologic tests were used, although serologic testing with skin PCR was almost as sensitive (92%). Plasma PCR was infrequently positive and provided no additional diagnostic value. Although culture is definitive and has a relatively high sensitivity, the results required a mean of 3.5 weeks to recovery. The combination of acute-phase serology and skin PCR was 75% sensitive, offering a practical and relatively rapid alternative for confirming clinical impression. The full battery of tests could be useful for patients with confusing clinical signs or for providing strong laboratory support for clinical studies of Lyme disease.

Comparison of the BBL CHROMagar Staph aureus agar medium to conventional media for detection of Staphylococcus aureus in respiratory samples.

Screening for Staphylococcus aureus has become routine in certain patient populations. This study is the first clinical evaluation of the BBL CHROMagar Staph aureus agar (CSA) medium (BD Diagnostics, Sparks, Md.) for detection of S. aureus in nasal surveillance cultures and in respiratory samples from cystic fibrosis (CF) patients. S. aureus colonies appear mauve on CSA. Other organisms are inhibited or produce a distinctly different colony color. S. aureus was identified from all media by slide coagulase, exogenous DNase, and mannitol fermentation assays. Susceptibility testing was performed using the agar dilution method. A total of 679 samples were evaluated. All samples were inoculated onto CSA. Nasal surveillance cultures were inoculated onto sheep blood agar (SBA) (BD Diagnostics), and samples from CF patients were inoculated onto mannitol salt agar (MSA) (BD Diagnostics). Of the 679 samples cultured, 200 organisms produced a mauve color on CSA (suspicious for S. aureus) and 180 were positive for S. aureus on SBA or MSA. Of 200 CSA-positive samples 191 were identified as S. aureus. Nine mauve colonies were slide coagulase negative and were subsequently identified as Staphylococcus lugdunensis (one), Staphylococcus epidermidis (three), Staphylococcus haemolyticus (one), and Corynebacterium species (four). CSA improved the ability to detect S. aureus by recovering 12 S. aureus isolates missed by conventional media. Of the 192 S. aureus isolates recovered, 122 were methicillin susceptible and 70 were methicillin resistant. Overall, the sensitivity and specificity of CSA in this study were 99.5 and 98%, respectively. There was no difference in the performance of the slide coagulase test or in susceptibility testing performed on S. aureus recovered from CSA compared to SBA or MSA. Our data support the use of CSA in place of standard culture media for detection of S. aureus in heavily contaminated respiratory samples.