In vitro activity of cefiderocol against carbapenem-resistant Acinetobacter baumannii carrying various ß-lactamase encoding genes.

OBJECTIVES: This study aimed to determine the in vitro efficacy of cefiderocol in carbapenem-resistant Acinetobacter baumannii (CRAB) isolates and evaluate the disk-diffusion (DD) method as an alternative method to broth-microdilution (BMD). METHODS: Totally 89 CRAB isolates were included. Cluster analysis was determined by Pulsed-Field Gel Electrophoresis (PFGE). Resistance genes; blaOXA-51, blaOXA-23, blaOXA-24, blaOXA-58,blaPER-1, blaNDM, blaIMP and mcr-1 were screened. Cefiderocol susceptibility testing was performed by both DD and BMD. Interpretation was made according to EUCAST and CLSI. Categorical agreement (CA), minor errors (mEs), major errors (MEs), and very major errors (VMEs) were determined. RESULTS: PFGE revealed 5 distinct pulsotypes; 86 of the isolates were extensively drug-resistant (XDR). All the isolates were negative for blaNDM, blaIMP, mcr-1, while positive for blaOXA-58 and blaOXA51. blaPER-1 was positive for 33.7%; blaOXA-23 for 74.2%; blaOXA-24 for 12.3%. According to CLSI, the MEs rate was 1.85%, mEs was 7.86% and there were no VMEs. According to EUCAST, MEs rate was 3.70%, there were no mEs and VMEs. CA was 91% for CLSI and 97.8% for EUCAST. MICs of cefiderocol against A. baumannii isolates ranged from 0.06 to > 128 mg/L, with MIC50 and MIC90 values of 0.5 and > 128 mg/L, respectively. CONCLUSIONS: Cefiderocol susceptibility was 60.7% in CRAB isolates. MIC50, MIC90 of blaPER-1 positive and blaPER-1 negative groups were > 128/>128 and 0.25/>128 mg/L. A correlation between the presence of blaPER-1 and cefiderocol resistance was observed (p < 0.0001). Among colistin-resistant isolates, the presence of blaPER-1 was 47.1% and 75% of them were resistant to cefiderocol respectively.

Evaluation of in vitro activity of ceftaroline, ceftobiprole and their combination with trimethoprim/sulfamethoxazole against MRSA isolates: a two center study.

There is an increasing need for new synergistic antimicrobial combinations against multidrug-resistant bacteria. Our objective was to evaluate the activity of ceftaroline, ceftobiprole and their combination with trimethoprim/sulfamethoxazole against methicillin-resistant Staphylococcus aureus (MRSA) isolates recovered at two centers in Turkey. Activities of ceftaroline and ceftobiprole were tested against 100 MRSA isolates using gradient diffusion method. Activities of ceftaroline and ceftobiprole in combination with trimethoprim/sulfamethoxazole against 20 selected isolates (including all isolates that were non-susceptible to ceftaroline or ceftobiprole, and randomly selected isolates) were investigated using MIC:MIC ratio method. Antimicrobial interactions were interpreted using the fractional inhibitory concentration (FIC) index. The MIC50/MIC90 values for ceftaroline and ceftobiprole were 0.75/1 and 1/1.5 mg/L, respectively. Ceftaroline and ceftobiprole susceptibility rates among 100 MRSA isolates were 94% and 96%, respectively. Ceftaroline, ceftobiprole and trimethoprim/sulfamethoxazole MICs of isolates were not increased when ceftaroline or ceftobiprole was combined with trimethoprim/sulfamethoxazole. Ceftobiprole- trimethoprim/sulfamethoxazole combination demonstrated additivity against 35%, whereas ceftaroline- trimethoprim/sulfamethoxazole combination demonstrated additivity against 10% of 20 MRSA isolates. The remaining interactions for MRSA isolates were indifference. Three (75%) of four ceftobiprole-resistant isolates became susceptible to ceftobiprole after adding trimethoprim/sulfamethoxazole. None of the ceftaroline non-susceptible isolates became susceptible to ceftaroline after adding trimethoprim/sulfamethoxazole. Ceftobiprole- trimethoprim/sulfamethoxazole combination may be a better treatment option than ceftaroline- trimethoprim/sulfamethoxazole combination for MRSA infections. Clinical studies are needed to confirm the results of our in vitro study.

Evaluation of the Lytic Activity of Various Phage Cocktails Against, ESBL-Producer, Non-Producer and Carbapenem-Resistant Escherichia coli Isolates.

Bacteriophages have been proposed as an alternative therapy for the treatment of bacterial infections. This research aims to determine the lytic activity of bacteriophage-cocktails (BC) against carbapenem-resistant (CR-EC), ESBL-producer (EP-EC), and non-producer (NP-EC) E. coli isolates. Related resistance genes in 87 E. coli isolates were screened by PCR. The efficacies of BCs were determined by spot test and lytic zones were evaluated from fully-confluent to opaque. MOIs of the BCs were compared for fully-confluent and opaque lytic zones. BCs were also evaluated in terms of their biophysical characteristics including latency, burst size, pH and temperature stabilities. Among EP-EC, 96.9% of the isolates carry blaCTX-M, 25% of them blaSHV and 15.6% of them carry blaTEM. All CR-EC isolates carried blaOXA-48, but not blaKPC and blaNDM. CR-EC isolates were the least susceptible for the each of four BCs. MOIs for ENKO, SES and INTESTI-phage forming fully-confluent zone in E. coli isolates EC3 (NP-EC), EC8 (EP-EC) and EC27 (NP-EC), respectively were 10, 100 and 1, respectively. MOIs for ENKO, SES and INTESTI opaque zone in EC19 (EP-EC), EC10 (EP-EC), EC1(NP-EC), respectively were 0.01, 0.01, 0.1 PFU/CFU, respectively. The MOI for PYO-phage forming a semi-confluent zone in EC6 (NP-EC) isolate was 1 PFU/CFU. The phages were thermally stable and tolerant to a wide pH range. Comparison of MOIs according to lysis zone characteristics demonstrated that the activities of phages in phage cocktails vary depending on the characteristics of each bacterial host. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01074-9.

Comparative in vitro activities of omadacycline, eravacycline and tigecycline against non-ESBL-producing, ESBL-producing and carbapenem-resistant isolates of K. pneumoniae.

Introduction. Extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae and carbapenem-resistant Enterobacteriaceae are characterized by the World Health Organization as pathogens for which new antibiotics are urgently needed. Omadacycline and eravacycline are two novel antibacterials within the tetracycline class.Gap Statement. There are limited data regarding the comparison of the activities of omadacycline, eravacycline and tigecycline against K. pneumoniae isolates with different antimicrobial susceptibility profiles.Aim. Our objective was to compare the in vitro activities of omadacycline, eravacycline and tigecycline against a collection of K. pneumoniae isolates, including non-ESBL-producing, ESBL-producing and carbapenem-resistant strains.Methodology. Ninety-four K. pneumoniae isolates, including 30 non-ESBL-producing, 30 ESBL-producing and 34 carbapenem-resistant (22 carrying bla OXA-48, 12 carrying bla NDM) strains were included in the study. ESBL and carbapenemase genes were detected by conventional PCR. Omadacycline, eravacycline and tigecycline MICs were determined by the gradient diffusion method and interpreted using US Food and Drug Administration (FDA)-defined breakpoints.Results. Overall, the percentage of tigecycline-susceptible strains (97.9 %) was higher than the percentage of omadacyline-susceptible (75.5 %) and eravacycline-susceptible (72.3 %) strains. The omadacycline and eravacycline susceptibility rates were 83.3 % among non-ESBL-producing isolates and 66.7 % among ESBL-producing isolates. The most common ESBL gene detected was blaCTX -M (90 %), followed by bla TEM (50 %) and bla SHV (50 %). The omadacycline and eravacycline susceptibility rate among isolates carrying bla TEM was 33.3 %, whereas it was 100 % among isolates that do not carry bla TEM. The omadacycline and eravacycline susceptibility rates among carbapenem-resistant isolates were 76.5 and 67.6 %, respectively. The omadacycline susceptibility rates among bla OXA-48-positive and bla NDM-positive isolates were 77.3 and 75.0 %, respectively. The eravacycline susceptibility rates among bla OXA-48-positive and bla NDM-positive isolates were 68.2 and 66.7 %, respectively. One carbapenem-resistant isolate was intermediate and one ESBL-producing isolate was resistant to tigecycline.Conclusion. Overall, tigecycline was the most active tetracycline against isolates. Omadacycline and eravacycline showed excellent activity against ESBL-producing K. pneumoniae isolates that do not carry bla TEM. Omadacycline showed reasonable activity against carbapenem-resistant K. pneumoniae isolates carrying bla OXA-48 or bla NDM.

Comparison of in vitro activities of plazomicin and other aminoglycosides against clinical isolates of Klebsiella pneumoniae and Escherichia coli.

OBJECTIVES: To compare the in vitro activity of plazomicin and two older aminoglycosides (gentamicin and amikacin) against 180 isolates of Escherichia coli and Klebsiella pneumoniae, including subsets of 60 non-ESBL-producing, 60 ESBL-producing and 60 carbapenem-resistant (46 carrying blaOXA-48, 11 carrying blaNDM and 3 carrying blaOXA-48 and blaNDM) strains. METHODS: MICs of plazomicin, gentamicin and amikacin were determined by a gradient diffusion method. Gentamicin and amikacin MICs were interpreted according to CLSI criteria and EUCAST breakpoint tables. Plazomicin MICs were interpreted using FDA-defined breakpoints. RESULTS: All non-ESBL-producing and ESBL-producing isolates were susceptible to plazomicin. The plazomicin susceptibility rate (71.7%) in carbapenem-resistant isolates was significantly higher than those observed for gentamicin (45%) and amikacin (56.7% and 51.7% according to CLSI and EUCAST breakpoints, respectively). Gentamicin, amikacin and plazomicin susceptibility rates (35.6% for gentamicin; 44.4% and 37.8% for amikacin according to CLSI and EUCAST breakpoints, respectively; 64.4% for plazomicin) in carbapenem-resistant K. pneumoniae were significantly lower than those observed for carbapenem-resistant E. coli isolates (73.3% for gentamicin; 93.3% for amikacin and plazomicin). Gentamicin, amikacin and plazomicin susceptibility rates for blaNDM-positive isolates were lower than those observed for blaOXA-48-positive isolates, but differences were not statistically significant. Among the isolates that were non-susceptible to both gentamicin and amikacin, the plazomicin susceptibility rate was less than 30%. CONCLUSIONS: Although plazomicin showed excellent in vitro activity against carbapenem-susceptible isolates, the plazomicin resistance rate increased to 35.6% among carbapenem-resistant K. pneumoniae and further increased to 45.5% among blaNDM-positive isolates.

In vitro activity of ceftolozane-tazobactam and ceftazidime-avibactam against clinical isolates of meropenem-non-susceptible Pseudomonas aeruginosa: A two-centre study.

OBJECTIVES: This study aimed to compare the activity of ceftazidime-avibactam (C/A), ceftolozane-tazobactam (C/T) and three anti-pseudomonal ß-lactams (piperacillin-tazobactam, ceftazidime and cefepime) against a collection of meropenem-non-susceptible Pseudomonas aeruginosa (P. aeruginosa) clinical isolates recovered from two centres in Turkey. METHODS: A total of 102 unique patient isolates of meropenem-non-susceptible P. aeruginosa were included in the study. MICs of antimicrobials were determined by the gradient diffusion method. RESULTS: Overall susceptibility rates for C/A and C/T were 83.3% and 82.4%, respectively. Both C/A and C/T had better activity than any one of the three anti-pseudomonal ß-lactams. According to the MIC50 values, C/T was the most potent agent against isolates. Although the susceptibility rates of isolates to C/T and C/A were similar, C/T (MIC50, 1 µg/mL) was four-fold more potent than C/A (MIC50, 4 µg/mL). The MIC50 values of C/A and C/T for the isolates that were non-susceptible to three ß-lactams were significantly higher than those for isolates that were non-susceptible to zero, one or two ß-lactams. Also, the C/A MIC50 value for the isolates that were non-susceptible to two ß-lactams was higher than that for isolates which were non-susceptible to one ß-lactam. CONCLUSIONS: C/A and C/T showed good activity against meropenem-non-susceptible P. aeruginosa isolates. However, resistance to these agents was not uncommon among these isolates. The overall ß-lactam susceptibility profile of isolates seems to have an effect on the probability of susceptibility to C/A and C/T. Antimicrobial susceptibility testing should be performed for C/A and C/T if these agents are considered for treatment of infections caused by meropenem-non-susceptible P. aeruginosa.

Clinical Strains of Chryseobacterium and Elizabethkingia spp. Isolated from Pediatric Patients in a University Hospital: Performance of MALDI-TOF MS-Based Identification, Antimicrobial Susceptibilities, and Baseline Patient Characteristics.

Our objective was to evaluate the performance of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) for identification of the Chryseobacterium and Elizabethkingia spp. isolated from pediatric patients at Hacettepe University Hospital using 16S rRNA gene sequencing as the gold standard and to determine the antimicrobial susceptibility patterns of the isolates and baseline characteristics of patients. All stored Chryseobacterium and Elizabethkingia spp. isolated from various clinical specimens (sputum, blood, and urine) of pediatric patients at Hacettepe University Hospital between 2012 and 2016 were included in this study. Minimum inhibitory concentrations of 10 antimicrobial agents were determined by Etest for all isolates. To determine the baseline characteristics of patients, medical records of all patients were retrospectively reviewed. In total, 18 isolates of Chryseobacterium spp. (16 C. indologenes, 2 C. gleum) and 5 isolates of Elizabethkingia spp. (3 E. meningoseptica, 2 E. anophelis) were identified by 16S rRNA sequencing. MALDI-TOF MS correctly identified 19 (82.6%) isolates to the species level. The quinolones (ciprofloxacin and levofloxacin), trimethoprim/sulfamethoxazole and piperacillin/tazobactam showed the highest spectrum of activity against the overall collection of isolates. Cystic fibrosis (CF) was the underlying disease in 81.8% of patients. To our knowledge, this study includes the largest number of Chryseobacterium spp. isolated from clinical specimens of pediatric patients in Turkey. In this study, we also report the first clinical isolate of E. anophelis in Turkey. Since, the majority of strains were isolated from patients with CF; larger, prospective clinical studies are needed to establish whether chryseobacteria could be considered as an emerging opportunistic pathogen in patients with CF.

The Prevalence of Vancomycin-Intermediate Staphylococcus aureus and Heterogeneous VISA Among Methicillin-Resistant Strains Isolated from Pediatric Population in a Turkish University Hospital.

There are limited data regarding the prevalence of vancomycin-intermediate Staphylococcus aureus (VISA)/heterogeneous VISA (hVISA) among pediatric population. Our objective was to determine the distribution of vancomycin and daptomycin minimum inhibitory concentrations (MICs) and explore the phenomenon of vancomycin MIC creep and the VISA/hVISA prevalence among the methicillin-resistant Staphylococcus aureus (MRSA) strains belonging to pediatric population by population analysis profile-area under the curve (PAP-AUC) and Etest macromethod. Vancomycin and daptomycin susceptibilities of 94 pediatric isolates of MRSA were tested by broth microdilution (BMD) and Etest methods. To determine the prevalence of VISA/hVISA, Etest macromethod and PAP-AUC was performed on all isolates. All isolates were susceptible to vancomycin and daptomycin by both BMD and Etest methods. Twenty-eight (29.8%) isolates had vancomycin MICs of 2 µg/ml by BMD. No increase in vancomycin MICs was observed over time. There were no VISA among 94 MRSA tested but 20 (21.3%) hVISA isolates were identified by PAP-AUC. Results of Etest macromethod were compared to PAP-AUC. Etest macromethod was 60.0% sensitive and 90.5% specific. The hVISA isolates represented 53.6% of isolates with vancomycin MICs of 2 µg/ml. Also, 75% of hVISA isolates had vancomycin MICs of 2 µg/ml. To our knowledge, this is the first study investigating the prevalence of VISA/hVISA among MRSA isolated from pediatric patients by PAP-AUC method. Based on our findings, MRSA isolates, which have vancomycin MIC of 2 µg/ml can be investigated for the presence of hVISA. In this study, daptomycin showed potent activity against all isolates and may represent a therapeutic option for MRSA infections.