Emergence of Colistin Resistance Among Carbapenem-Resistant MDR <i>Pseudomonas aeruginosa</i> Isolates from Northeast Iran: Determination of MIC Values

Background: Clinical antibiotic susceptibility testing (AST) interpretations based on minimum inhibitory concentrations (MIC) breakpoints are important for both clinical decision making and some reportable condition criteria. Standardization of MIC breakpoints across clinical laboratories is lacking; AST instruments are often validated for outdated Clinical and Laboratory Standards Institute (CLSI) MIC breakpoint guidelines. In this study, we analyzed the agreement between the reported clinical laboratory AST interpretations and the guideline CLSI interpretation. Methods: Clinical laboratory AST data collected from the Multisite Gram-Negative Surveillance Initiative (MuGSI) carbapenem-resistant Enterobacterales (CRE) surveillance program in Tennessee between 2019 and 2021 were utilized. MIC values from the clinical instrument were used to calculate CLSI standard interpretations following the 2019–2021 CLSI M100 guidelines. Agreement between the clinical laboratory and CLSI interpretations of the reported MIC values were measured using a weighted Cohen κ calculated in SAS version 9.4 software. Total matches were isolates with identical CLSI and clinical laboratory interpretations. Results: In total, 14 antibiotics were assessed. Of those, 9 antibiotics had at least moderate agreement (κ > 0.41) between interpretations. Agreement between the clinical laboratory and the CLSI interpretations were near perfect (κ > 0.81) for 3 antibiotics. Agreement between the clinical laboratory and the CLSI interpretations were poor for cefazolin (0.06) and ertapenem (0.14). Cefotaxime (−0.07) was the only antibiotic that suggested no agreement. Conclusions: Of the antibiotics included in the analysis, 36% had less than moderate agreement between clinical laboratory and CLSI AST interpretations. Given the increases in antimicrobial resistance globally and the emphasis placed on antibiotic stewardship, standardization across clinical AST panels should be prioritized. Inconsistencies have the potential to contribute to inappropriate antibiotic use in addition to under- or overidentification of reportable conditions, including CRE.Disclosures: None

The Clinical and Laboratory Standards Institute (CLSI) updated its antimicrobial susceptibility testing interpretation criteria for Enterobacteriaceae. This study assessed the effects of clinical breakpoint changes in the CLSI 2009 to 2012 guidelines on antibiotic susceptibility testing reports. In total, 2,076 non-duplicate clinical isolates of Enterobacteriaceae were analyzed. The disk diffusion method was used for susceptibility testing. The CLSI 2009-12 clinical breakpoints were applied to determine susceptibility of cefotaxime and ertapenem. Combined-disk testing was used for phenotypic confirmation of extended-spectrum beta-lactamase (ESBL) production. In total, Enterobacteriaceae resistance rates to cefotaxime increased from 13.1% using the CLSI 2009 guidelines to 23.6% with the CLSI 2010-12 guidelines, and the resistance rates to ertapenem were 0.4%, 1.0% and 0.8% with CLSI 2009, 2011 and 2012, respectively. Based on the 2010-12 CLSI criteria, all ESBL-producing Escherichia coli and Klebsiella pneumoniae were resistant to cefotaxime. Marked differences in susceptibility to ertapenem between the 2009 CLSI criteria and 2012-12 CLSI criteria were noted in ESBL-producing K. pneumoniae. Breakpoints changes in the updated CLSI guidelines resulted in higher resistance rates to cefotaxime and ertapenem. In addition, the effects were different in individual Enterobacteriaceae species. As a result, clinicians may opt to use alternative antimicrobial agents. Upon implementation of the newer CLSI guidelines, laboratories should be aware of the possible consequences and closely monitor the effects.

Clinical and Laboratory Standards Institute (CLSI) recommends a blood culture contamination (BCC) threshold of <3%, with ≤1% considered optimal. However, there is not a standardized definition of BCC, and the effect of multiple definitions on BCC rates or what definitions laboratories use remain unknown. We surveyed 52 hospitals and analyzed 362,078 blood cultures (BCx) collected 1 September 2019 to 31 August 2021 from 62 intensive care units (ICUs) and 231 wards from 48 of these hospitals. We calculated and compared BCC rates using the College of American Pathologists (CAP) or CLSI criteria (both utilize a limited number of skin commensals to define BCC) and the comprehensive National Healthcare Safety Network (NHSN) commensal list. We characterized factors associated with BCC and related outcomes (central-line associated bloodstream infection [CLABSI] and vancomycin use). BCC, BCx positivity, and single BCx rates were monitored by 100%, 39%, and 21% of hospitals, respectively. Hospitals used CAP (65%), CLSI (17%), and NHSN (17%) criteria to define BCC. Mean BCC rate by CAP (CAP-BCC) was 1.38% for ICUs and 0.96% for wards. BCC rates remained similar by CLSI criteria but increased when using NHSN list. Sharing BCC data outside of the laboratory, measuring additional BCx quality indicators, and limiting central catheter-drawn BCx were associated with lower BCC rates. BCC was associated with higher CLABSI rates in ICUs. This study demonstrated variability in laboratory practices and opportunities to optimize BCx stewardship.IMPORTANCEBlood culture contamination (BCC) is associated with patient harm and unnecessary use of healthcare resources. BCC thresholds have been established; however, multiple BCC definitions exist. There is limited data on how BCC rates differ depending on the BCC definition used, what definitions laboratories most commonly use, or their approach to other blood cultures (BCx) quality indicators such as single rates or BCx positivity. A cross-sectional multicenter survey and analysis of BCx data from intensive care unit and wards revealed that most laboratories did not track single BCx or BCx positivity rates and that there was variability in how BCC was defined. Additionally, BCC rates were influenced by the definition used. BCC was associated with increased central-line associated bloodstream infection rates.

Relationship between the distribution of cefepime minimum inhibitory concentrations and detection of extended-spectrum β-lactamase production among clinically important Enterobacteriaceae isolates obtained from patients in intensive care units in Taiwan: Results from the Surveillance of Multicenter Antimicrobial Resistance in Taiwan (SMART) in 2007

BackgroundCarbapenem-resistant Acinetobacter baumannii (CRAB) represents a devastating and growing global threat, calling for new antibiotic treatments. In Korea, the challenge of treating CRAB is compounded by high nosocomial acquisition rates and limited availability of novel antibiotics. Minocycline, a semisynthetic tetracycline derivative, has been proposed as a therapeutic option for CRAB infections. Nonsusceptibility to minocycline may occur through the efflux pump, TetB. The prevalence of tetB in A. baumannii has increased, along with higher minocycline minimum inhibitory concentrations (MICs). We aimed to evaluate minocycline susceptibility rates in clinical strains of CRAB, and the association between tetB carriage and minocycline susceptibility across different genotypes.Materials and MethodsRepresentative CRAB blood isolates were collected from Asan Medical Center, Seoul. Minocycline susceptibility was assessed using the Clinical and Laboratory Standards Institute (CLSI) breakpoint (≤4 mg/L) and the proposed pharmacokinetics (PK)/pharmacodynamics (PD) breakpoint (≤1 mg/L). Tigecycline was used as a comparator, and its susceptibility breakpoint for Enterobacterales defined by EUCAST was applied (≤0.5 mg/L). The presence of tetB was detected by PCR, and multilocus sequence typing (MLST) was performed using seven housekeeping genes.ResultsOf the 160 CRAB blood isolates, 83.8% were susceptible to minocycline by the CLSI criteria, and 50.6% were PK-PD susceptible by the PK-PD criteria. The minocycline minimum inhibitory concentration (MIC)50/MIC90 was 1/8 mg/L. tetB was present in 49% of isolates and was associated with a higher minocycline MIC (MIC50/90 2/8 mg/L vs. 1/2 mg/L). No clear correlation was observed between tetB positivity and tigecycline MIC. Nine MLSTs were identified, with significant differences in tetB carriage rates between the major sequence types. Notably, ST191, associated with non-tetB carriage and greater susceptibility to minocycline, declined over the study period (P=0.004), while ST451, associated with tetB carriage, increased.ConclusiontetB was present in 49% of CRAB isolates and was associated with higher MICs and non-susceptibility by both CLSI and PK-PD criteria. However, absence of tetB was not a reliable predictor of minocycline PK-PD susceptibility. Additionally, shifts over time towards genotypes with reduced minocycline susceptibility were observed. Further research is needed to correlate these findings with clinical outcomes and identify additional resistance mechanisms.

Background: Vancomycin-resistant Enterococcus (VRE) is an important cause of nosocomial infection with Enterococcus faecium causing most of the VRE infections. Widespread use of glycopeptides in health care facilities has led to the development of VRE and enterococcal infections with high-level resistance to aminoglycosides, beta-lactamase production and glycopeptide (including vancomycin) resistance are difficult to treat and often pose a therapeutic challenge to health care facilities. Aims and Objectives: This study aimed to determine the antibiotic susceptibility pattern of Enterococcus species from various clinical specimens and to find out the occurrence rate of vancomycin-resistant enterococci. Materials and Methods: This study was conducted at the Department of Microbiology of Tamralipto Government Medical College and Hospital, East Midnapore, West Bengal. A total of 688 clinical samples were the total sample size taken. Isolation and identification of Enterococcus spp. were done by standard microbiological procedures such as culture, Gram staining, and suitable biochemical tests were conducted. Antibiotic susceptibility testing was done by the Kirby–Bauers disc diffusion method on Mueller–Hinton agar and results were interpreted according to Clinical and Laboratory Standards Institute (CLSI) guidelines 2023. Teicoplanin sensitivity was performed for those isolates showing resistance to vancomycin. For strains showing resistance to vancomycin by the Kirby–Bauers disc diffusion method, vancomycin minimum inhibitory concentrations (MIC) were performed by E-test (Hi media) with MIC breakpoints between 4 and 32 as per CLSI criteria. This was compared with the control strain of American Type Culture Collection Enterococcus faecalis 29212 as per CLSI 2023 guidelines. Results: A total of 48 Enterococcus isolates were obtained from 688 clinical samples; 31 (8.05%) were detected from 385 urine samples, 9 (6.72%) were detected from 134 blood samples, 5 (5.15%) were detected from 97 pus/wound swab, and 3 (4.17%) were detected from 72 bronchoalveolar lavage fluid samples. Among the 48 Enterococcus isolates, 13 (27.08%) were vancomycin-resistant out of which nine were E. faecalis and four were E. faecium. Enterococcus species showed maximum resistance toward ciprofloxacin followed by ampicillin and maximum sensitivity toward teicoplanin and linezolid. Conclusion: Implementation of strict infection control measures, antimicrobial policies, and proper surveillance are required to identify, contain, and treat VRE infections to reduce mortality and morbidity.

Background/Objectives: While new methods for measuring antimicrobial susceptibility have been associated with improved patient outcomes, they should also be validated using standard protocols for error rates and other test metrics. The objective of this study was to validate a novel susceptibility assay for complicated and recurrent urinary tract infections (UTIs): pooled antibiotic susceptibility testing (P-AST). This assay was compared to broth microdilution (BMD) and disk diffusion (DD), following Clinical and Laboratory Standards Institute (CLSI) guidelines for assessment of error rates and agreement. Methods: This study analyzed consecutive fresh clinical urine specimens submitted for UTI diagnostic testing. Upon receipt, the urine samples were subjected in parallel to standard urine culture and multiplex polymerase chain reaction (M-PCR) for microbial identification and quantification. Specimens with the same monomicrobial non-fastidious bacteria detected by both M-PCR and standard urine culture (SUC) underwent standard antibiotic susceptibility testing (AST) and P-AST antibiotic susceptibility testing. Analysis was also undertaken to assess the presence of heteroresistance for specimens with P-AST-resistant and BMD/DD consensus-susceptible results. Results: The performance measures without correction for heteroresistance showed essential agreement (EA%) of ≥90%, very major errors (VMEs) of <1.5%, and major errors (MEs) of <3.0% for P-AST, all meeting the threshold guidelines established by CLSI for AST. The categorical agreement (CA%) also met acceptable criteria (>88%), as the majority of the errors were minor (mEs) with essential agreement. The very major and major error rates for P-AST decreased to <1.0% when heteroresistance was accounted for. Conclusions: The P-AST assay methodology is validated within acceptable parameters when compared to broth microdilution and disk diffusion using CLSI criteria.

Cefiderocol is a new antibiotic used to treat infections with antibiotic resistant Gram-negative bacilli. The impact of differences between Mueller-Hinton agar (MHA) brands on susceptibility testing is underexplored. Compounding the implementation of cefiderocol susceptibility testing is a lack of harmonization between different regulatory body breakpoint criteria. We performed Kirby-Bauer disk diffusion using BD, Hardy, and Remel MHA, in addition to broth microdilution for Acinetobacter baumannii (n = 25), Enterobacterales (n = 25), Stenotrophomonas maltophilia (n = 24), and Pseudomonas aeruginosa (n = 23). We analyzed disk diffusion diameters and minimum inhibitory concentrations using interpretive criteria from the Clinical and Laboratory Standards Institute (CLSI), US Food and Drug Administration (FDA), and the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Breakpoint criteria impacted interpretation of susceptibly testing results, for example with the broth microdilution we found 8% (2/25) of A. baumannii isolates change interpretation between CLSI and EUCAST and 32% (8/25) change between CLSI and FDA, 12% (3/25) of Enterobacterales change between CLSI and EUCAST, 13% (3/23) of P. aeruginosa interpretations change between CLSI and FDA, and 4% (1/25) S. maltophilia change between CLSI and FDA. There was a significant difference between the zone disk diffusion diameters for P. aeruginosa and S. maltophilia between Hardy and BD; which changed interpretation (using CLSI criteria) for 8.7% (2/23) for P. aeruginosa but 0% (0/24) for S. maltophilia. Breakpoint criteria impact cefiderocol susceptibility testing interpretation for broth microdilution and disk diffusion. Choice of MHA brand can also affect result interpretation.

A retrospective study was conducted at a Taiwanese medical center to characterize bloodstream infections caused by IMP-8 metallo-β-lactamase (MBL)-producing Enterobacteriaceae isolates and to assess the need for laboratory detection of IMP producers. We analyzed 37 patients infected with IMP-8 producers (two Escherichia coli, nine Klebsiella pneumoniae, 25 Enterobacter cloacae, and one Citrobacter freundii) and 107 patients infected with non-IMP-8 producers (eight E. coli, 26 K. pneumoniae, 70 E. cloacae, and three C. freundii) that were interpreted as carbapenem-nonsusceptible based on the updated Clinical and Laboratory Standards Institute (CLSI) 2010 guidelines. Only 18 (48.6 %) of the IMP-8 producers were regarded as potential carbapenemase producers based on the CLSI 2012 guidelines. The production of extended-spectrum β-lactamases (ESBLs) was more common in the MBL group (73.0 %) than in the non-MBL group (41.1 %). There were no significant differences in carbapenem susceptibilities, clinical characteristics, carbapenem use for empirical and definitive treatment, and mortality rates between the two groups. Eighteen IMP-8 producers could be deemed as resistant to all carbapenems [minimum inhibitory concentration (MIC) of any carbapenem ≥2 μg/mL]; patients with these isolates had a lower, but non-significant, 28-day mortality rate (27.8 %) than patients infected with non-MBL producers having similar carbapenem MICs (39.0 %) (p = 0.41). A multivariate analysis revealed severity of acute illness as the single independent variable associated with both 7-day and 28-day mortality rates (p < 0.01) for infections caused by Enterobacteriaceae with decreased carbapenem susceptibilities. Our findings suggest that the clinical detection of IMP-producing Enterobacteriaceae is not required even when the "old" CLSI criteria are used.

Background: Clinical laboratories perform antimicrobial susceptibility testing (AST) primarily by determining the minimum inhibitory concentration (MIC) for an organism–antimicrobial combination and comparing it with established breakpoints to generate interpretations. The Antimicrobial Resistance (AR) Option of CDC’s National Healthcare Safety Network (NHSN) permits hospitals to submit clinical isolate AST data, including test values and interpretations (Figure 1). The Clinical and Laboratory Standards Institute (CLSI) periodically revises breakpoints, but their adoption by clinical laboratories can be delayed, potentially affecting national AR surveillance data accuracy. Using MIC values, instead of clinical laboratory interpretations, can improve surveillance data accuracy and overcome misclassification due to delayed uptake of revised breakpoints. We evaluated the completeness and consistency of MIC data submitted to the AR Option for fluoroquinolone-resistant Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA). Methods: We included data on (1) E. coli isolates tested for ciprofloxacin or levofloxacin susceptibility and (2) S. aureus isolates tested for oxacillin or cefoxitin susceptibility in 2022 and reported by October 1, 2023. We evaluated completeness among isolates reporting a final AST interpretation as the proportion of isolates reporting both an MIC value and interpretation. We evaluated consistency using percent agreement comparing the laboratory’s MIC interpretation (classified as resistant or not resistant) with the interpretation derived by applying 2021 CLSI M100 breakpoints to the MIC values reported for the same isolate. Results: Across 974 hospitals, fluoroquinolone MICs and interpretations were reported for 172,012/393,359 E. coli isolates (43.7%), and oxacillin or cefoxitin MICs and interpretations were reported for 38,519/79,372 S. aureus isolates (48.5%). Of isolates with both MIC values and interpretations, 157,902 (91.8%) E. coli and 7,808(79.7%) S. aureus isolates had MICs that could be classified as resistant or non-resistant (i.e., intermediate or susceptible) per CLSI breakpoints (Figure 2). The remaining MICs were unclassifiable (reported as intervals spanning CLSI breakpoints, e.g., ≤1 μg/ml ciprofloxacin for E. coli). Among isolates with classifiable MICs, the agreement between the clinical laboratory and CLSI-based interpretation was 99.5% for E. coli and 99.7% for S. aureus. Conclusion: MIC values and interpretations were available for

The aim of this study was to investigate the effectiveness of ceftaroline against agents frequently isolated from respiratory tract and wound infections. The study included a total of 250 strains isolated from various clinical specimens, among which were Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysagalactiae, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catharralis. The bacteria were identified using the matrix-assisted laser desorption/ionization time-of-flight method and conventional methods. The bacteria's antibiotic susceptibility was tested using appropriate broth microdilution. Mueller-Hinton broth with 4% lysed horse blood, Haemophilus test medium broth, and Mueller-Hinton broth were used. Ceftaroline fosamil results at the minimum inhibitory concentration (MIC) were evaluated using Clinical and Laboratory Standards Institute (CLSI) criteria. For quality assurance, E. coli ATCC 35218, S. aureus ATCC 29213, S. aureus ATCC 43300, S. pneumoniae ATCC 49619, H. influenzae ATCC 49766, H. influenzae ATCC 10211, and H. influenzae ATCC 49247 standard strains were used. According to CLSI criteria, resistance was not detected in any strains. Due to the absence of CLSI criteria for M. catharralis, the susceptibility state for this bacterium was not evaluated. The various strains' MIC50-MIC90 values were as follows: for S. pyogenes, 0.015-0.06; for S. agalactiae, 0.03-0.125; for S. dysagalactiae, 0.03-0.06; for S. pneumoniae, 0.06-0.125; for H. influenzae, 0.015-0.125; and for M. catharralis, 0.5-1. The results indicate that ceftaroline is quite effective against bacteria that are frequently isolated from respiratory tract and wound infections.

We have previously reported on the susceptibility and epidemiology of Clostridioides difficile isolates from six geographically dispersed medical centers in the United States. This current survey was conducted with isolates collected in 2020-2021 from six geographically dispersed medical centers in the United States, with specific attention to susceptibility to ridinilazole as well as nine comparators. C. difficile isolates or stools from patients with C. difficile antibiotic-associated diarrhea were collected and referred to a central laboratory. After species confirmation of 300 isolates at the central laboratory, antibiotic susceptibilities were determined by the agar dilution method [M11-A9, Clinical and Laboratory Standards Institute (CLSI)] against the 10 agents. Ribotyping was performed by PCR capillary gel electrophoresis on all isolates. Ridinilazole had a minimum inhibitory concentration (MIC) 90 of 0.25 mcg/mL, and no isolate had an MIC greater than 0.5 mcg/mL. In comparison, fidaxomicin had an MIC 90 of 0.5 mcg/mL. The vancomycin MIC 90 was 2 mcg/mL with a 0.7% resistance rate [both CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria]. The metronidazole MIC 90 was 1 mcg/mL, with none resistant by CLSI criteria, and a 0.3% resistance rate by EUCAST criteria. Among the 50 different ribotypes isolated in the survey, the most common ribotype was 014-020 (14.0%) followed by 106 (10.3%), 027 (10%), 002 (8%), and 078-126 (4.3%). Ridinilazole maintained activity against all ribotypes and all strains resistant to any other agent tested. Ridinilazole showed excellent in vitro activity against C. difficile isolates collected between 2020 and 2021 in the United States, independent of ribotype.

Objective: To determine the variations in minimal inhibitory concentrations (MIC) of Azithromycin amongst Salmonella typhi isolates. Study Design: Cross-sectional study. Place and Duration of Study: Department of Microbiology, Combined Military Hospital, Lahore Pakistan, from Jan to Dec 2020. Methodology: Three hundred and eighty-four samples yielding the growth of Salmonella typhi were processed. Antibiotic susceptibility testing was done using the Kirby-Bauer Disk Diffusion technique, and the MIC of Azithromycin was determined using the E-strip method. Clinical and Laboratory Standards Institute (CLSI) recommended that MIC breakpoints be used for susceptibility testing of Azithromycin. Results: Of 384 tested isolates, 103(26.8%) were multidrug-resistant (MDR). Resistance to Ciprofloxacin was as high as 367(95.6%) isolates, whereas extensively drug-resistant (XDR) isolates were calculated to be 204(53.1%). No resistance against Azithromycin was observed. All the isolates were in the susceptible MIC range of 0.5 and 8 μg/ml. The lowest MIC observed was 0.5 μg/ml by 12(5%) of the isolates. The highest MIC value of 8 μg/ml was observed in 6(1.5%) isolates, all of which were XDR. 231(60.2%) isolates had one μg/ml MIC, followed by MIC 4 μg/ml of 72(18.8%) isolates. The mean MIC value of all the isolates was calculated to be 1.82±1.3μg/ml. Conclusion: The rise in XDR Salmonella typhi could lead to Azithromycin resistance. Antimicrobial stewardship is of prime importance, and Azithromycin MICs should be reported to keep the trends in check.

BACKGROUND: Methicillin resistance and biofilm-producing Staphylococci are emerging as multidrug-resistant strains narrowing the efficacy of antimicrobial therapy. Although vancomycin is used as the drug of choice to treat such isolates, different studies worldwide have documented the emergence of strains that are intermediately susceptible or resistant to this antibiotic. OBJECTIVE: The study aimed to determine the minimum inhibitory concentration of vancomycin to methicillin-resistant and biofilm-producing staphylococci isolated from different clinical specimens. METHODS: 375 staphylococci isolated from different clinical specimens over one year were included in the study. Biofilm formation was determined by the Tissue culture plate method (TCP), and ica genes were identified by Polymerase Chain Reaction (PCR). Antibiotic susceptibility and methicillin resistance were done following Clinical and Laboratory Standards Institute (CLSI) guidelines. The minimum inhibitory concentration (MIC) of vancomycin in all isolates was determined by the agar dilution method. RESULTS: Among 375 Staphylococci studied, 43% and 57% represented S. aureus and Coagulase-Negative Staphylococci (CNS), respectively. The rate of Methicillin-Resistant S. aureus (MRSA) and Methicillin-Resistant Coagulase Negative Staphylococci (MRCNS) were 81.4% and 66.8% respectively and determined by the disc diffusion method. The most potential antibiotics were tetracycline and chloramphenicol showing sensitivity to more than 90% isolates. The Minimum Inhibitory Concentration (MIC) value of oxacillin for staphylococci ranged from 0.125-32 μg/ml. Oxacillin agar diffusion method showed 51.6% and 79.9% isolates as MRSA and MRCNS, respectively, revealing a very high percentage of S. aureus and CNS isolates as methicillin-resistant. All isolates had susceptible vancomycin MICs that ranged from 0.125-2 μg/ml. Two S. aureus isolated from Central Venous Catheter (CVC) and catheter specimens were detected with intermediate susceptibility to vancomycin. Similarly, three CNS isolated from blood, CVC, and wound/pus (w/p) were intermediately susceptible to vancomycin. Strong biofilm formation was observed in 22.1% of clinical isolates, and the ica gene was detected among 22.9% of isolates. Only one S. aureus detected as a biofilm producer by the TCP method was found to have intermediate susceptibility to vancomycin. CONCLUSIONS: The increment in vancomycin MIC among methicillin-resistant and biofilm-producing staphylococci is alarming. Strict control measures to prevent methicillin-resistant isolates spread and routine surveillance for vancomycin-resistant isolates must be incorporated in hospitals to prevent antimicrobial treatment failure.

BackgroundCefiderocol (CFDC) has been developed for the treatment of serious infections caused by drug-resistant aerobic Gram-negative pathogens, including carbapenem-resistant (CR) Pseudomonas aeruginosa (CRPA). The current CFDC susceptibility breakpoints for P. aeruginosa differ between US Food and Drug Administration (FDA) and Clinical and Laboratory Standards Institute (CLSI) (Table). Data characterizing the impact of CFDC minimum inhibitory concentrations (MICs) on the clinical responses of patients treated with CFDC for CRPA are sparse.MethodsWe reviewed patients treated with compassionate-use CFDC (2 g, q8h or renally adjusted dosages) for infections caused by CRPA with no alternative treatment options. CFDC minimum inhibitory concentrations (MICs) were evaluated according to CLSI guidelines in iron-depleted cation-adjusted Müller–Hinton broth for available CRPA isolates. We then assessed physician-reported clinical responses to CFDC therapy and stratified results by CFDC MIC. ResultsThere were 71 patients overall with CRPA treated with CFDC. Treatment duration ranged from 1 to 132 days. For the subset of 33 patients for whom CFDC MIC values were available, the most common infection sites were the respiratory tract (n=15), blood (n=12), and urinary tract (n=4). Patients could have had an infection at ≥1 sites and in other locations. CFDC MIC range was ≤0.03– >64 µg/mL. The modal MIC value was 2 µg/mL (n=13; Table). CRPA isolates were susceptible to CFDC in 13/33 patients (39.4%) based on the FDA breakpoint (MIC ≤1 µg/mL) and in 31/33 patients (93.9%) based on the CLSI breakpoint (MIC ≤4 µg/mL). Clinical response was reported for 15/18 patients (83.3%) who had infections with CFDC MICs of 2–4 µg/mL, organisms that are considered susceptible by CLSI but not by FDA breakpoints (Table). Clinical response was reported in 6/13 patients (46.1%) with infections with CFDC MIC ≤1 µg/mL and in 1 of 2 patients (50.0%) with CFDC MIC ≥8 µg/mL (Table). 21 (63.6%) patients survived to Day 28 and there were no trends in mortality by CFDC MIC.ConclusionClinical response rate was high for CRPA infections with CFDC MICs of 2–4 µg/mL, supporting the higher CLSI susceptibility breakpoint.DisclosuresMichael J. Satlin, MD, MS, Achaogen (Consultant)Allergan (Research Grant or Support)BioFire Diagnostics (Research Grant or Support)Merck (Research Grant or Support)Shionogi (Consultant) David Fam, PharmD, Shionogi (Employee) Roger Echols, MD, Shionogi (Consultant) Christopher Longshaw, PhD, Shionogi (Employee) Miki Takemura, MS, SHIONOGI & CO., LTD. (Employee) Yoshinori Yamano, PhD, Shionogi (Employee)