ICU Isolates Research Articles

Antibiotic susceptibility profile of Pseudomonas species isolated from clinical specimens to access, watch and reserve drugs across various hospital settings at a tertiary care hospital of central India

Background and Objectives: Over the last decade, hospital-acquired infections, particularly in the critical care setting, have become more common, with Gram-negative bacterial infections having the highest prevalence. This study aims to determine the prevalence and antibiotic susceptibility pattern of Pseudomonas species to WHO’s, aware class of antibiotics, which are commonly prescribed across various ICU’s, medical and surgical wards of our tertiary care teaching hospital. Materials and Methods: This prospective study conducted from January 2021 to June 2022 at a tertiary care centre of cen- tral India identified Pseudomonas species from clinical samples using standard procedures and antimicrobial susceptibility testing performed as per Clinical Laboratory Standards Institute (CLSI) guidelines (M100; 32th Edition). Results: A total of 1490 non duplicate Pseudomonas species isolates were grown from 21,019 culture positive clinical sam- ples, of which 1247 were Pseudomonas aeruginosa. Out of these 1247 Pseudomonas aeruginosa 384 were MDR (30.7%). Pseudomonas aeruginosa were most commonly isolated from the pus samples (85%). ICU isolates were significantly more resistant to antibiotics than those from other units. P. aeruginosa strains from ICUs showed the highest rates of resistance to ceftazidime (93.9%). Reserve drug colistin showed good susceptibility (98.2%). All the 18 colistin resistant strains were found to be negative for plasmid mediated mcr-1,2,3 genes. Conclusion: The study shall help to generate and disseminate the data so that proper antibiotic policy can be made for judi- cious use of Access, Watch and Reserve antibiotics and antibiotic de-escalation plan can be put forth.

Staphylococcus capitis Bloodstream Isolates: Investigation of Clonal Relationship, Resistance Profile, Virulence and Biofilm Formation.

Staphylococcus capitis has been recognized as a relevant opportunistic pathogen, particularly its persistence in neonatal ICUs around the world. Therefore, the aim of this study was to describe the epidemiological profile of clinical isolates of S. capitis and to characterize the factors involved in the persistence and pathogenesis of these strains isolated from blood cultures collected in a hospital in the interior of the state of São Paulo, Brazil. A total of 141 S. capitis strains were submitted to detection of the mecA gene and SCCmec typing by multiplex PCR. Genes involved in biofilm production and genes encoding enterotoxins and hemolysins were detected by conventional PCR. Biofilm formation was evaluated by the polystyrene plate adherence test and phenotypic resistance was investigated by the disk diffusion method. Finally, pulsed-field gel electrophoresis (PFGE) was used to analyze the clonal relationship between isolates. The mecA gene was detected in 99 (70.2%) isolates, with this percentage reaching 100% in the neonatal ICU. SCCmec type III was the most prevalent type, detected in 31 (31.3%) isolates and co-occurrence of SCCmec was also observed. In vitro biofilm formation was detected in 46 (32.6%) isolates but was not correlated with the presence of the ica operon genes. Furthermore, biofilm production in ICU isolates was favored by hyperosmotic conditions, which are common in ICUs because of the frequent parenteral nutrition. Analysis of the clonal relationship between the isolates investigated in the present study confirms a homogeneous profile of S. capitis and the persistence of clones that are prevalent in the neonatal ICU and disseminated across the hospital. This study highlights the adaptation of isolates to specific hospital environments and their high clonality.

Pseudomonas aeruginosa antibiotic susceptibility profiles, genomic epidemiology and resistance mechanisms: a nation-wide five-year time lapse analysis.

Pseudomonas aeruginosa healthcare-associated infections are one of the top antimicrobial resistance threats world-wide. In order to analyze the current trends, we performed a Spanish nation-wide high-resolution analysis of the susceptibility profiles, the genomic epidemiology and the resistome of P.aeruginosa over a five-year time lapse. A total of 3.180 nonduplicated P.aeruginosa clinical isolates from two Spanish nation-wide surveys performed in October 2017 and 2022 were analyzed. MICs of 13 antipseudomonals were determined by ISO-EUCAST. Multidrug resistance (MDR)/extensively drug resistance (XDR)/difficult to treat resistance (DTR)/pandrug resistance (PDR) profiles were defined following established criteria. All XDR/DTR isolates were subjected to whole genome sequencing (WGS). A decrease in resistance to all tested antibiotics, including older and newer antimicrobials, was observed in 2022 vs 2017. Likewise, a major reduction of XDR (15.2% vs 5.9%) and DTR (4.2 vs 2.1%) profiles was evidenced, and even more patent among ICU isolates [XDR (26.0% vs 6.0%) and DTR (8.9% vs 2.6%)] (p<0.001). The prevalence of Extended-spectrum β-lactamase/carbapenemase production was slightly lower in 2022 (2.1%. vs 3.1%, p=0.064). However, there was a significant increase in the proportion of carbapenemase production among carbapenem-resistant strains (29.4% vs 18.1%, p=0.0246). While ST175 was still the most frequent clone among XDR, a slight reduction in its prevalence was noted (35.9% vs 45.5%, p=0.106) as opposed to ST235 which increased significantly (24.3% vs 12.3%, p=0.0062). While the generalized decrease in P.aeruginosa resistance, linked to a major reduction in the prevalence of XDR strains, is encouraging, the negative counterpart is the increase in the proportion of XDR strains producing carbapenemases, associated to the significant advance of the concerning world-wide disseminated hypervirulent high-risk clone ST235. Continued high-resolution surveillance, integrating phenotypic and genomic data, is necessary for understanding resistance trends and analyzing the impact of national plans on antimicrobial resistance. MSD and the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea-NextGenerationEU.

Development of a combination antibiogram for empirical treatments of Pseudomonas aeruginosa at a university-affiliated teaching hospital.

The significantly higher mortality rate in the critical illness patients with Pseudomonas aeruginosa (PA) infection is linked to inappropriate selecting of empirical treatment. Traditional local antibiogram provides clinicians the resistant rate of a single antimicrobial agent to the pathogen in the specific setting. The information is valuable to the clinicians in selecting suitable empirical antibiotic therapy. However, traditional local antibiogram can only provide information for single agent empirical antibiotic not combination regimens. The combination antibiogram should be developed to facilitate the selection of appropriate antibiotics to broader the coverage rate of resistant PA. The susceptibility to the β-lactam antibiotics (piperacillin/tazobactam (PTZ), ceftazidime, cefepime, imipenem, or meropenem) or to those administered in combination with an aminoglycoside (gentamicin or amikacin) or fluoroquinolone (ciprofloxacin or levofloxacin) was calculated. The chi-square test was used to compare the differences of combination coverage rates between non-ICU and ICU isolates. 880 PA isolates were isolated during study period. The susceptibility of single agents ranged from 83.1% to 89.7%. The combination regimens containing amikacin provide the highest cover rate (98.9%-99.1%) and those containing levofloxacin provide less coverage rate (92.3%-93.9%). The susceptibility to five β-lactam single agents in ICU isolates significantly lower than non-ICU isolates. The non-ICU isolates exhibited significantly higher susceptibility to the PTZ-gentamicin (p = 0.002) and ceftazidime-gentamicin (p = 0.025) than ICU isolates. Our results support the use of aminoglycosides instead of fluoroquinolones as additive agents in empirical combination treatments for patients with critical infections caused by PA.

Activity of imipenem/relebactam against Enterobacterales and Pseudomonas aeruginosa in Spain. SMART 2016-2020.

To determine susceptibility to the novel β-lactam/β-lactamase inhibitor combination imipenem/relebactam in clinical isolates recovered from intra-abdominal (IAI), urinary (UTI), respiratory (RTI) and bloodstream (BSI) infections in the SMART (Study for Monitoring Antimicrobial Resistance Trends) study in SPAIN during 2016 - 2020. Broth microdilution MICs for imipenem/relebactam and comparators were determined by a central laboratory against isolates of Enterobacterales and Pseudomonas aeruginosa. MICs were interpreted using EUCAST-2021 breakpoints. In total, 5,210 Enterobacterales and 1,418 P. aeruginosa clinical isolates were analyzed. Imipenem/relebactam inhibited 98.8% of Enterobacterales. Distinguishing by source of infection susceptibility was 99.1% in BSI, 99.2% in IAI, 97.9% in RTI, and 99.2% in UTI. Of intensive care unit isolates (ICU) 97.4% were susceptible and of non-ICU isolates 99.2% were susceptible. In Enterobacterales, activity against Class A, Class B and Class D carbapenemases was 96.2%, 15.4% and 73.2%, respectively. In P. aeruginosa, imipenem/relebactam was active in 92.2% of isolates. By source of infection it was 94.8% in BSI, 92.9% in IAI, 91.7% in RTI, and 93.1% in UTI. An 88.7% of ICU isolates and 93.6% of non-ICU isolates were susceptible to imipenem/relebactam. Imipenem/relebactam remained active against P. aeruginosa ceftazidime-resistant (76.3%), cefepime-resistant (73.6%), imipenem-resistant (71.5%) and piperacillin-resistant (78.7%) isolates. Of all multidrug-resistant or difficult-to-treat resistance P. aeruginosa isolates, 75.1% and 46.2%, respectively, were susceptible to imipenem/relebactam. Imipenem/relebactam showed high rates of susceptibility in Enterobacterales and P. aeruginosa isolates from different sources of infection as well as depending on patients' location (ICU or non-ICU scenarios).

347. Azole Activity against Filamentous Fungi Causing Invasive Infections in Patients from ICU and Non-ICU Units (2017-2021)

Abstract Background Invasive fungal infection (IFI) is associated with high mortality rates in critically ill patients. Appropriate antifungal treatment is crucial for managing IFI. We evaluated the in vitro activity of isavuconazole (ISC), itraconazole (ITC), posaconazole (PSC), and voriconazole (VRC) against contemporary moulds from ICU and non-ICU patients. Methods 1,226 moulds causing IFI (386/840 from ICU/non-ICU patients, respectively) were consecutively collected (1/patient) in 43 worldwide hospitals from 2017-2021 and susceptibility tested by CLSI broth microdilution. CLSI interpretation criteria were applied. Pneumonia was the predominant infection type among ICU (81.6%) and non-ICU (71.8%) patients. Results Aspergillus spp. was the most common mould (87.6%/80.5%). A. fumigatus (AFM; 76.0%/65.4% of Aspergillus), A. section Flavi (ASF; 9.2%/10.9%), and A. section Nigri (ASN; 7.4%/13.6%) were the top 3 Aspergillus groups. ISC inhibited 94.2%/91.2%, 100.0%/98.6%, and 96.0%/96.7% of AFM, ASF, and ASN from ICU/non-ICU, respectively, at the epidemiological cut-off values. Similar activities were noted for ISC, PSC, ITC, and VRC against AFM from ICU (MIC50/90 range, 0.25-1/0.5-1 mg/L) and non-ICU (MIC50/90 range, 0.5-1/0.5-2 mg/L) isolates. No difference in the azole activities was noted against ASF from ICU (MIC50/90 range, 0.5/0.5-1 mg/L) and non-ICU (MIC50/90, 0.5/0.5-1 mg/L) or ASN from ICU (MIC50/90 range, 0.5-2/1-4 mg/L) and non-ICU (MIC50/90 range, 0.5-2/1-4 mg/L) isolates. VRC-non-susceptible (NS) AFM isolates were detected in 9.3% of ICU and 9.0% of non-ICU isolates. Among VRC-NS AFM from ICU/non-ICU, 58.3%/27.5% were wildtype (WT) to ISC, 50.0%/25.0% were ITC-WT, and 75.0%/50.0% remained VRC-WT, respectively. VRC was the most active azole against Scedosporium spp. (SCE) but was less active against Mucorales (MUC) than the other azoles. All azoles showed limited activity against Fusarium spp. (FUS). No difference on azole activities against SCE, MUC, and FUS were noted from ICU and non-ICU isolates. Conclusion ISC was active against Aspergillus isolates from ICU and non-ICU, including against VRC-NS AFM from ICU. Azoles displayed similar activity against moulds from ICU and non-ICU units. Disclosures Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Paul Rhomberg, BS, MT(ASCP), Cidara: Grant/Research Support|Pfizer: Grant/Research Support Paul Rhomberg, BS, MT(ASCP), Cidara: Grant/Research Support|Pfizer: Grant/Research Support Beth A. Schaefer, BA, MT(ASCP), Pfizer: Grant/Research Support Michael A. Pfaller, MD, Pfizer: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support.

2052. Temporal and Geographical Prevalence of Carbapenem-Resistant Pseudomonas aeruginosa and the In Vitro Activity of Ceftolozane/Tazobactam and Comparators in Taiwan – SMART 2012-2020

Abstract Background Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is listed as a critical pathogen by World Health Organization (WHO). Using clinical isolates collected in Taiwan as part of the global SMART surveillance program, we evaluated the trend of CRPA prevalence in recent nine years (2012-2020) as well as in vitro activity of ceftolozane/tazobactam (C/T) and comparators against CRPA collected from ICU vs non-ICU wards from 2016 to 2020. Methods Between 2012-2020, Pseudomonas aeruginosa (PA) isolates were collected from nine sites in Taiwan (2 in Northern, 3 in Central and 4 in Southern Taiwan). MICs were determined and interpreted based on CLSI broth microdilution guidelines and 2021 CLSI breakpoints. PCR screening and β-lactamase gene sequencing were performed for isolates non-susceptible to imipenem or imipenem/relebactam or C/T. Results During the study period, a total of 2639 PA isolates were collected. Among these, 448 isolates were resistant to either imipenem or meropenem (17.0%). Yearly prevalence rate of CRPA increased from 12.3% in 2012 to 22.8% in 2020: 12.3% in 2012 (14/114), 11.5% in 2013 (16/139), 11.5% in 2014 (13/113), 12.2% in 2015 (41/336), 15.5% in 2016 (57/367), 15.9% in 2017 (68/428), 20.4% in 2018 (73/357), 19.4% in 2019 (75/386) and 22.8% (91/399) in 2020. Hospitals in Northern Taiwan had higher CRPA prevalence rate (22.8%, 131/574) compared to those in Central (15.7%, 126/802) and Southern Taiwan (15.1%, 191/1263). Percentage susceptibility of CRPA isolates to C/T from 2016 to 2020 showed 89.47% (51/57) in 2016, 79.41% (54/68) in 2017, 93.2% (68/73) in 2018, 90.7% (68/75) in 2019 and 98.9% (90/91) in 2020. For ICU vs. Non-ICU CRPA isolates, the susceptibility to C/T were 88.3% vs.93.8%, 77.8% vs. 82.5%, 92.3 % vs. 92.9%, 87.1% vs.93.2% and 100% vs. 98.26%, in 2016,2017, 2018, 2019 and 2020, respectively. Conclusion During the period of 2012-2020, the yearly prevalence of CRPA in Taiwan hospitals increased from 12.3% to 22.8%. The high prevalence and increasing trend of CRPA warrant continuous monitoring of evolving antibiotic resistance in Taiwan. Disclosures Tai-Chin Hsieh, MBBS, MSD Taiwan: Advisor/Consultant|MSD Taiwan: Employee of MSD Taiwan|MSD Taiwan: Stocks/Bonds.

1672. Antimicrobial Activity of Cefepime-Taniborbactam and Comparators Against Clinical Isolates from ICU and Non-ICU Patients; 2018-2020 Global Surveillance

Abstract Background Taniborbactam is a novel cyclic boronate-based broad-spectrum β-lactamase inhibitor with selective direct inhibitory activity against both serine- and metallo-β-lactamases. Taniborbactam restores the activity of cefepime against many difficult to treat organisms, including cephalosporin- and carbapenem-resistant Enterobacterales (EB) and P. aeruginosa (PA). The activity of cefepime-taniborbactam (FTB) and comparator agents was evaluated against clinical isolates of EB and PA from a 2018-2020 global surveillance study. Methods 16,742 isolates of EB and PA were collected from patients in wards designated ICU and non-ICU in 2018-2020. MICs of FTB and comparators were determined by the CLSI reference method. Resistant (R) phenotypes were based on 2022 CLSI breakpoints. Multidrug resistant (MDR) was defined as resistance to at least one agent from ≥3 drug classes. Provisional susceptible (S) breakpoints of ≤8 µg/mL and ≤16 µg/mL were applied for FTB for comparative purposes only. Results FTB had potent activity against EB, with MIC90s of 0.25 µg/mL for isolates from non-ICU patients and 0.5 µg/mL for isolates from ICU patients (Table). At least 99.2% of all EB from both wards were inhibited by ≤8 µg/mL FTB. FTB maintained activity against R phenotypes of EB in both ward types, with 90.3% to 98.1% of isolates inhibited at ≤8 µg/mL. FTB had potent activity against PA, with MIC90 values of 8 µg/mL and inhibiting ≥94.0% of isolates at ≤8 µg/mL for both ICU and non-ICU isolates. FTB maintained activity against R phenotypes of PA in both ward types, with 71.0% to 83.7% of isolates inhibited at ≤8 µg/mL and 84.7% to 92.5% inhibited at ≤16 µg/mL. %S to comparator agents against the R subsets ranged from 1.6% to 92.6% for EB, and 36.0% to 68.4% for PA. Against the particularly challenging subset of MDR PA from ICU patients, FTB was the most active agent tested as it inhibited 73.5/84.7% of isolates at ≤8/≤16 µg/mL compared to 43.1%S to CZA and 36.0%S to C/T. Conclusion Cefepime-taniborbactam demonstrated potent in vitro activity against EB and PA from ICU and non-ICU wards, including resistant subsets of isolates. This supports the continued development of FTB as a potential new treatment option for infections due to resistant Gram-negative pathogens. Disclosures All Authors: No reported disclosures.

Carbapenem-resistant Pseudomonas aeruginosa: an assessment of frequency of isolation from ICU versus non-ICU, phenotypic and genotypic profiles in a multinational population of hospitalized patients

BackgroundHistorically, multi-drug resistant organisms have been associated with the ICU setting. The present study sought to define the frequency of isolation from ICU versus non-ICU, phenotypic and genotypic profiles of carbapenem-resistant Pseudomonas aeruginosa (CR-PA) from a global cohort.MethodsMulticenter surveillance study (17 centers from 12 countries) including 672 CR-PA isolates from 2019 to 2021. Phenotypic carbapenemase testing was assessed. Genotypic carbapenemase testing was conducted (CarbaR and CarbaR NxG) to detect β-lactamases. Broth microdilution MICs were established for ceftazidime, cefepime, ceftolozane/tazobactam, and ceftazidime/avibactam.Results59% of CR-PA were isolated from patients outside the ICU. The most common source in ICU and non-ICU patients was respiratory (55% and 30%, respectively). In the ICU, 35% of isolates were phenotypically carbapenemase-positive versus 29% for non-ICU. VIM was the most common carbapenemase (54% and 44%, respectively) followed by GES (27% and 28%, respectively). Susceptibility to ceftazidime or cefepime were relatively low in ICU (39% and 41% of isolates, respectively) and non-ICU (47% and 52% of isolates, respectively). Ceftolozane/tazobactam and ceftazidime/avibactam were more active with 56% and 66% of isolates susceptible in the ICU while 65% and 76% in non-ICU, respectively. When carbapenemase-negative, 86% and 88% of ICU isolates were susceptible to ceftolozane/tazobactam and ceftazidime/avibactam. Similarly, in the carbapenemase-negative, non-ICU isolates 88% and 92% of isolates were susceptible, respectively.ConclusionAlthough multidrug resistant pathogens are often regarded as a challenge in the ICU population, the majority of CR-PA were isolated from non-ICU patients. Implementing phenotypic/genotypic testing will assist in guiding treatment. Carbapenem-resistance in P. aeruginosa should be regarded as a surrogate for MDR and this phenotype is increasingly prevalent outside the ICU.

Molecular Characterization and Antibiogram of Acinetobacter baumannii Clinical Isolates Recovered from the Patients with Ventilator-Associated Pneumonia.

A 2-year prospective study carried out on ventilator-associated pneumonia (VAP) patients in the intensive care unit at a tertiary care hospital, Hail, Kingdom of Saudi Arabia (KSA), revealed a high prevalence of extremely drug-resistant (XDR) Acinetobacter baumannii. About a 9% increase in the incidence rate of A. baumannii occurred in the VAP patients between 2019 and 2020 (21.4% to 30.7%). In 2019, the isolates were positive for IMP-1 and VIM-2 (31.1% and 25.7%, respectively) as detected by PCR. In comparison, a higher proportion of isolates produced NDM-1 in 2020. Here, we observed a high proportion of resistant ICU isolates towards the most common antibiotics in use. Colistin sensitivity dropped to 91.4% in the year 2020 as compared to 2019 (100%). Thus, the finding of this study has a highly significant clinical implementation in the clinical management strategies for VAP patients. Furthermore, strict implementation of antibiotic stewardship policies, regular surveillance programs for antimicrobial resistance monitoring, and screening for genes encoding drug resistance phenotypes have become imperative.

Molecular Detection of OXA-type Carbapenemases among Acinetobacter baumannii Isolated from Burn Patients and Hospital Environments

Background:Acinetobacter baumanniiis known as one of the major causes of nosocomial infections, especially in intensive care units and burn patients. The emergence of antimicrobial resistance in burn wound bacterial pathogens is a severe health crisis. Detection of carbapenem resistance and genetic elements inA. baumanniiassociated with burn patients and hospital environments play a key role in the control and alerting in clinical settings.Purpose:In this study, the prevalence of OXA-type carbapenemases was investigated inA. baumanniistrains isolated from burn patients and from a hospital environment in Tehran, 2021.Methods:A total of 85 non-duplicateA. baumanniiisolates (53 from various surfaces of the hospital environment and 32 from burn patients) were recovered in the Burns Hospital in Tehran. TheA. baumanniiisolates were screened for antibiotic susceptibility and the presence of the most common OXA-type carbapenemase genes.Results:A. baumanniiwas isolated from 38.5% of hospital patient burn wounds and 22.1% of surfaces, including burn units (15.6%) and intensive care units (52.4%). Antibiotic susceptibility results showed that (100%) of burn patient isolates were resistant to imipenem, while (100%) of ICU isolates and (96.8%) of burn isolates were resistant to imipenem. All clinical isolates were identified as MDR and XDR, whereas all (100%) and 98.1% of environmental isolates were identified as MDR and XDR, respectively. All studiedA. baumanniiisolates carriedblaOXA-51-likegene. Moreover, 50 (94.3%) and 49 (92.5%) of environmental isolates, 32 (100%) and 30 (93.7%) of burn patient isolate harboredblaOXA-23-likeandblaOXA-24/40–likegenes, respectively. None of the isolates carried theblaOXA-58orblaOXA-143genes and all isolates had at least 2 OXA-type carbapenemase genes.Conclusion:Our results suggest that surfaces in the hospital environment, particularly in ICUs, are contaminated with MDR or XDRA. baumanniistrains. They may be considered a potential reservoir for the colonization of hospital patients. In addition, OXA-type carbapenemases, including OXA-23-like and OXA-24/40-like, appear to be one of the major mechanisms of carbapenem resistance in the clinical and environmentalA. baumanniistrains.

In vitro activity of ceftolozane/tazobactam against Gram‐negative isolates collected from ICU patients with lower respiratory tract infections in seven Asian countries—SMART 2017–2019

ObjectivesAntimicrobial resistance is one of the top 10 global public-health threats. Especially high rates of resistance have been reported for isolates from ICU patients, requiring expanded treatment options in this setting. We evaluated the activity of ceftolozane/tazobactam and comparators against Gram-negative isolates collected from patients with lower respiratory tract infections (LRTIs) in ICUs in seven Asian countries. MethodsIn 2017–2019, up to 100 consecutive, aerobic Gram-negative LRTI isolates were collected per year at each of 37 hospitals. MICs were determined using the Clinical and Laboratory Standards Institute reference broth microdilution method. ResultsOverall, ceftolozane/tazobactam was active against 72% of 1408 Enterobacterales and 86% of 761 Pseudomonas aeruginosa isolates. Susceptibility to the non-carbapenem β-lactam comparators, including piperacillin/tazobactam, was 52–67% among Enterobacterales isolates, and the activity of all β-lactam comparators, including meropenem, was 57–70% among P. aeruginosa. Ceftolozane/tazobactam maintained activity against 61% of meropenem-nonsusceptible and 64% of piperacillin/tazobactam-nonsusceptible P. aeruginosa. At the country-level, ceftolozane/tazobactam activity ranged from >90% against Enterobacterales from Hong Kong and South Korea to <64% in Thailand and Vietnam, and from >90% against P. aeruginosa from South Korea, Malaysia, Philippines and Taiwan to <75% in Thailand and Vietnam. Correspondingly, the proportions of carbapenemase-positive isolates among Enterobacterales and P. aeruginosa isolates were highest in Thailand and Vietnam. ConclusionCeftolozane/tazobactam provides a potential treatment option for ICU patients in Asia, which is especially important considering the reduced activity of commonly used β-lactams against the studied ICU isolates. Knowledge of local resistance patterns should inform empirical therapy decision-making.

1294. Activity of Ceftolozane/Tazobactam and Comparators against Resistant Pseudomonas aeruginosa Isolates from Patients with Respiratory Tract or Bloodstream Infections in ICU and non-ICU settings – SMART United States 2018-2019

Abstract Background ICUs are considered hotspots of antimicrobial resistance. Treatment of ICU patients with infections caused by P. aeruginosa (Pa) is especially challenging. When patients fail to improve on therapy with first-line antipseudomonal agents such as piperacillin/tazobactam (P/T) or cefepime (FEP), clinicians often escalate to a carbapenem. Ceftolozane/tazobactam (C/T) is an antipseudomonal cephalosporin (combined with a β-lactamase inhibitor) that was specifically developed to have enhanced antibacterial activity against Pa. We evaluated the activity of C/T and comparators against Pa isolates collected from patients with respiratory tract (RTI) or bloodstream infections (BSI) in ICU and non-ICU settings. Co-resistance (e.g., activity of C/T or meropenem (MEM) when Pa is nonsusceptible (NS) to P/T or FEP) was also evaluated to help inform common clinical scenarios. Methods In 2018-2019, 24 US clinical labs each collected up to 100 RTI and 50 BSI consecutive gram-negative pathogens per year as part of the global SMART surveillance program. Only the 1195 Pa isolates collected from patients in ICU or non-ICU hospital wards were included in this report; 1078 and 117 isolates were from patients with RTI and BSI, respectively. MICs were determined using CLSI broth microdilution and breakpoints. Results Susceptibility for P/T, FEP, and MEM was generally lower among isolates from patients in ICU than non-ICU wards by 5-14 percentage points, while the difference was ≤3 percentage points for C/T (Table). C/T maintained activity against 96% of ICU isolates, 17-23 percentage points higher than P/T, MEM, or FEP. MEM inhibited 40% of P/T-NS and 34% of FEP-NS ICU isolates, while C/T maintained activity against 81-88% of P/T-NS, FEP-NS, and MEM-NS isolates from ICU patients (Table, Figure). Results Table Conclusion High co-resistance in Pa was seen with P/T, FEP, and MEM especially among ICU isolates. These data suggest that routine escalation to a carbapenem may not be optimal in some critically ill patients not responding to empiric therapy. Among the tested β-lactam antibiotics, C/T showed the highest activity against Pa isolates overall and among resistant phenotypes. Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) C. Andrew DeRyke, PharmD, Merck &amp; Co., Inc. (Employee, Shareholder) Kelly Harris, PharmD, BCPS, Merck &amp; Co. Inc (Employee) Katherine Young, MS, Merck (Employee) Mary Motyl, PhD, Merck &amp; Co., Inc. (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)

1223. In Vitro Activity of Ceftazidime-Avibactam and Comparator Agents Against Enterobacterales from ICU and Non-ICU Wards Collected in Latin America and Globally as part of the ATLAS Surveillance Program 2017-2019

BackgroundCeftazidime-avibactam (CAZ-AVI) is a β-lactam/non-β-lactam β-lactamase inhibitor combination with activity against Enterobacterales producing class A, C and some class D β-lactamases. Resistance caused by these β-lactamases is especially high in ICUs. This study evaluated the in vitro activity of CAZ-AVI and comparators against Enterobacterales isolates from patients in ICU and non-ICU wards.MethodsNon-duplicate clinical isolates were collected in 2017-2019 from patients in Asia/Pacific, Europe, Latin America, and Middle East/Africa. Susceptibility testing was performed using CLSI broth microdilution and interpreted using CLSI 2021 and FDA (tigecycline) breakpoints. PCR and sequencing were used to determine the β-lactamase genes present in all isolates with meropenem (MEM) MIC >1 µg/ml, and Escherichia coli, Klebsiella spp. and Proteus mirabilis with aztreonam or ceftazidime MIC >1 µg/ml.ResultsThe activity of CAZ-AVI and comparators is shown in the table. Susceptibility rates among global Enterobacterales were generally lower for isolates from patients in ICU than non-ICU wards, but this difference was small for CAZ-AVI, which inhibited >96% of isolates from both ward types. Among MEM-nonsusceptible (NS) isolates, CAZ-AVI was active against 62.3% and 65.6% of ICU and non-ICU isolates, respectively, and 36.3% and 33.2%, respectively, carried metallo-β-lactamases (MBLs). CAZ-AVI inhibited >97% of MEM-NS MBL-negative isolates collected globally. Antimicrobial activity against all Enterobacterales from both ICU and non-ICU wards in Latin America (LA) was generally similar to the global average. Among MEM-NS isolates, antimicrobial activity of CAZ-AVI was >10 percentage points higher in LA than the global average among isolates from both ward types, at least partly because of a lower proportion of MBL-positive isolates in this subset (24.4% and 22.0% in ICU and non-ICUs, respectively). CAZ-AVI inhibited >98% of MEM-NS MBL-negative isolates from LA.Results Table ConclusionCAZ-AVI provides a valuable treatment option for infections caused by Enterobacterales that do not carry MBLs, including those from patients in ICU wards, where antimicrobial resistance is typically higher.Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Gregory Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)

Analysis of Blood Culture Data Influences Future Epidemiology of Bloodstream Infections: A 5-year Retrospective Study at a Tertiary Care Hospital in India

ABSTRACTBackgroundBlood cultures are the most significant samples received in a microbiology laboratory. Good quality control of pre-analytic, analytic, and post-analytic stages can have a significant impact on patient outcomes. Here, we present the improvements brought about by reviewing blood culture data with clinicians at a tertiary care institute in India.MethodsFour-year blood culture data (phase I—February 2014–February 2018) were shared with clinicians in the clinical grand round. Several take-home messages were discussed in a quiz format, and a number of holistic quality control measures were implemented at different levels. Based on observable changes in blood culture reports, another dataset was analyzed and compared in phase II (April 2018–April 2019).ResultsIn phase II, the blood culture contamination rate improved from 6 to 2% along with four times reduction in ICU isolates and three times increased isolation of salmonellae and pneumococci. The development of resistance in Klebsiella pneumoniae to carbapenems and piperacillin–tazobactam was reduced. Colistin resistance in ICU isolates hovered around 15%. Vaccine-preventable pneumococcal serotypes were predominant in the under-five age-group. Typhoidal salmonellae were more commonly isolated from adults with 50% showing sensitivity to pefloxacin and 97% to ampicillin, chloramphenicol, and cotrimoxazole. Candida parapsilosis was the leading non-albicans Candida (NAC). Fluconazole resistance was observed in 50% of NAC.ConclusionReviewing blood culture data with clinicians mutually helped us to improve the overall quality of blood culture reports. It had a major impact on epidemiological trends and thus, found to be superior to just sharing an antibiogram with the clinicians.How to cite this articleSharma A, Samaddar A, Maurya A, Hada V, Narula H, Shrimali T, et al. Analysis of Blood Culture Data Influences Future Epidemiology of Bloodstream Infections: A 5-year Retrospective Study at a Tertiary Care Hospital in India. Indian J Crit Care Med 2021;25(11):1258–1262.

Antimicrobial Susceptibility Sensitivity Pattern in Positive Urine Culture for Urinary Tract Pathogens from Tertiary Care Hospital

Hospital specific monitoring studies aims to determine the prevalence of the type of microorganisms that causes urinary infections and to assess the antimicrobial sensitivity pattern. A hospital based short term prospective cross-sectional study was conducted at Sagar Hospital, Bengaluru from August to October 2020. Antimicrobial susceptibility in MIC test was performed for the isolated pathogens by using automated VITEK compact method and stratification was done according to ICU and NON-ICU patients with over 260 urine culture tests of the suspected in-patient for urinary tract infection. All antimicrobial susceptibility data was analyzed using WHONET software 5.6. Sixty-six urine culture tests showed culture positive, 41 from non-ICU and 23 from ICU. Gram-negative bacilli E.Coli (61% in ICU, 52% IN non-ICU) was the most prevalent bacterium, followed by Klebsiella pneumoniae ss. pneumoniae (9% in ICU, 20% IN non-ICU), and Candida albicans 9% prevalence was seen only in ICU isolates. The study shows that the rate of resistance towards ampicillin (100%) was high among gram negative isolates and penicillin (100%) among gram positive isolates. The susceptibility was favorable towards polymixinB, colistin in gram negative organisms and nitrofurantoin, vancomycin in gram positive organisms. The present study revealed that E.Coli is the predominant bacterial pathogen. It also demonstrates there is an increasing resistance to ampicillin (88.2%) and ESBL (90%) among UTI pathogens. While, polymixin B (100%) and colistin was found most effective among gram negative and nitrofurantoin was most effective among gram positive organisms.&#x0D; Keywords: Antibiotic, antimicrobial resistance, urinary tract infection

Ceftolozane/Tazobactam and Imipenem/Relebactam Cross-Susceptibility Among Clinical Isolates of Pseudomonas aeruginosa From Patients With Respiratory Tract Infections in ICU and Non-ICU Wards-SMART United States 2017-2019.

BackgroundCarbapenem-nonsusceptible and multidrug-resistant (MDR) P. aeruginosa, which are more common in patients with lower respiratory tract infections (LRTIs) and in patients in intensive care units (ICUs), pose difficult treatment challenges and may require new therapeutic options. Two β-lactam/β-lactamase inhibitor combinations, ceftolozane/tazobactam (C/T) and imipenem/relebactam (IMI/REL), are approved for treatment of hospital-acquired/ventilator-associated bacterial pneumonia.Methods The Clinical and Laboratory Standards Institute–defined broth microdilution methodology was used to determine minimum inhibitory concentrations (MICs) against P. aeruginosa isolates collected from patients with LRTIs in ICUs (n = 720) and non-ICU wards (n = 914) at 26 US hospitals in 2017–2019 as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program.ResultsSusceptibility to commonly used β-lactams including carbapenems was 5–9 percentage points lower and MDR rates 7 percentage points higher among isolates from patients in ICUs than those in non-ICU wards (P < .05). C/T and IMI/REL maintained activity against 94.0% and 90.8% of ICU isolates, respectively, while susceptibility to all comparators except amikacin (96.0%) was 63%–76%. C/T and IMI/REL inhibited 83.1% and 68.1% of meropenem-nonsusceptible (n = 207) and 71.4% and 65.7% of MDR ICU isolates (n = 140), respectively. Among all ICU isolates, only 2.5% were nonsusceptible to both C/T and IMI/REL, while 6.7% were susceptible to C/T but not to IMI/REL and 3.5% were susceptible to IMI/REL but not to C/T.ConclusionsThese data suggest that susceptibility to both C/T and IMI/REL should be considered for testing at hospitals, as both agents could provide important new options for treating patients with LRTIs, especially in ICUs where collected isolates show substantially reduced susceptibility to commonly used β-lactams.

Activity of ceftolozane/tazobactam against Gram-negative isolates from patients with lower respiratory tract infections \u2013 SMART United States 2018\u20132019

BackgroundCeftolozane/tazobactam (C/T) is approved in 70 countries, including the United States, for the treatment of patients with hospital-acquired and ventilator-associated bacterial pneumonia caused by susceptible Gram-negative pathogens. C/T is of particular importance as an agent for the treatment of multidrug-resistant (MDR) Pseudomonas aeruginosa infections. The current study summarizes 2018–2019 data from the United States on lower respiratory tract isolates of Gram-negative bacilli from the SMART global surveillance program. The CLSI reference broth microdilution method was used to determine in vitro susceptibility of C/T and comparators against isolates of P. aeruginosa and Enterobacterales.ResultsC/T inhibited 96.0% of P. aeruginosa (n = 1237) at its susceptible MIC breakpoint (≤4 μg/ml), including > 85% of meropenem-nonsusceptible and piperacillin/tazobactam (P/T)-nonsusceptible isolates and 76.2% of MDR isolates. Comparator agents demonstrated lower activity than C/T against P. aeruginosa: meropenem (74.8% susceptible), cefepime (79.2%), ceftazidime (78.5%), P/T (74.4%), and levofloxacin (63.1%). C/T was equally active against ICU (96.0% susceptible) and non-ICU (96.7%) isolates of P. aeruginosa. C/T inhibited 91.8% of Enterobacterales (n = 1938) at its susceptible MIC breakpoint (≤2 μg/ml); 89.5% of isolates were susceptible to cefepime and 88.0% susceptible to P/T. 67.1 and 86.5% of extended-spectrum β-lactamase (ESBL) screen-positive isolates of Klebsiella pneumoniae (n = 85) and Escherichia coli (n = 74) and 49.6% of MDR Enterobacterales were susceptible to C/T. C/T was equally active against ICU (91.3% susceptible) and non-ICU (92.6%) Enterobacterales isolates.ConclusionData from the current study support the use of C/T as an important treatment option for lower respiratory tract infections including those caused by MDR P. aeruginosa.

Longitudinal Study of the Drug Resistance in Klebsiella pneumoniae of a Tertiary Hospital, China: Phenotypic Epidemiology Analysis (2013-2018).

PurposeMulti-drug resistant Klebsiella pneumoniae (MDR KP) is spreading worldwide and has posed a huge medical burden to public health. However, studies on drug resistance surveillance of KP, especially MDR KP, with a large longitudinal sample size in a tertiary hospital are rare. This study aims to investigate phenotypic epidemiology characteristics of 4128 KP isolates in a Chinese tertiary hospital covering a period of 5 years.MethodsAll the KP clinical isolates were retrospectively collected from a tertiary hospital in Hunan province of China from Jan 5, 2013 to Jul 24, 2018. All the isolates were identified by MALDI-TOF MS analysis. Twenty-four antimicrobial agents were tested by antimicrobial susceptibility testing. Fisher exact test and logistic regression were used to analyze the association between clinical factors and antimicrobial non-susceptibility for seven second-choice antimicrobials.ResultsA total of 4128 KP isolates were collected in our study. The non-susceptible rates (NSRs) to ertapenem, imipenem and tigecycline increased considerably from 2013 to 2018 (13.6% to 28.6%, 10.1% to 28.9%, 10.8% to 46.5%, respectively). Amikacin presents the lowest NSR among 3 aminoglycosides (3.8–22.8%). The multi-drug NSRs among KP isolates to second-choice antimicrobials (88.6–100%) were higher than to all drugs (68.0%). The NSRs varied significantly among departments and sample sources. Higher ETP/IPM/AK NSRs (39.8/39.7/30.6%) were observed in Intensive Care Unit, and ETP/IPM non-susceptible isolates tended to distribute in cerebrospinal fluid. From 2015 to 2017, the NSRs of ETP, IPM, and AK showed an opposite trend of seasonal fluctuations to SXT.ConclusionHigher multi-drug resistance (MDR) rates were observed in KP isolates to second-choice antimicrobials than to others, among which MDR rates to carbapenems or AK are the highest. A unique pattern of MIC and time distributions of MDR were observed. Clinical factors including gender were correlated with MDR rates of KP. Isolates in ICU and CSF showed higher NSRs in carbapenems which should be paid more attention to, and temporal distribution of NSRs was observed.

1570. In Vitro Activity of Ceftazidime-Avibactam and Comparator Agents Against Enterobacterales from ICU and Non-ICU Wards Collected in Latin America and Globally as part of the ATLAS Surveillance Program 2017-2018

BackgroundCeftazidime-avibactam (CAZ-AVI) is a β-lactam/non-β-lactam β-lactamase inhibitor combination with activity against Enterobacterales producing class A, C and some class D β-lactamases. Resistance caused by these β-lactamases is especially high in ICUs. This study evaluated the in vitro activity of CAZ-AVI and comparators against Enterobacterales isolates from patients in ICU and non-ICU wards.MethodsNon-duplicate clinical isolates were collected in 2017-2018 from patients in Asia/Pacific, Europe, Latin America, and Middle East/Africa. Susceptibility testing was performed using CLSI broth microdilution and interpreted using CLSI 2020 and FDA (tigecycline) breakpoints. PCR and sequencing were used to determine the β-lactamase genes present in all isolates with meropenem (MEM) MIC >1 µg/ml, and Escherichia coli, Klebsiella spp. and Proteus mirabilis with aztreonam or ceftazidime MIC >1 µg/ml.ResultsThe activity of CAZ-AVI and comparators is shown in the table. Susceptibility rates among global Enterobacterales were generally lower for isolates from patients in ICU than non-ICU wards, but this difference was small for CAZ-AVI, which inhibited ≥97% of isolates from both ward types. Among MEM-nonsusceptible (NS) isolates, CAZ-AVI was active against 66.5% and 68.1% of ICU and non-ICU isolates, respectively (of which 31.8% and 30.8%, respectively, carried metallo-β-lactamases [MBLs]). CAZ-AVI inhibited >97% of MEM-NS MBL-negative isolates collected globally. Antimicrobial activity against all Enterobacterales from both ICU and non-ICU wards in Latin America (LA) was generally similar to the global average. Among MEM-NS isolates, antimicrobial activity of CAZ-AVI and TGC was higher in LA than the global average among isolates from both ward types, at least partly because of a lower proportion of MBL-positive isolates in this subset (15.8% and 17.9% in ICU and non-ICUs, respectively). CAZ-AVI inhibited 100% of MEM-NS MBL-negative isolates from LA.Table ConclusionCAZ-AVI provides a valuable treatment option for infections caused by Enterobacterales that do not carry MBLs, including those among patients in ICU wards, where antimicrobial resistance is typically higher.DisclosuresSibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Greg Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)