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.

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.

Staphylococcal cassette chromosome mec (SCCmec) characterization and panton-valentine leukocidin gene occurrence for methicillin-resistant Staphylococcus aureus in Turkey, from 2003 to 2006.

Methicillin-resistant Staphylococcus aureus (MRSA) cause serious community-acquired and nosocomial diseases all over the world. We determined the SCCmec types and occurrence of the PVL gene by using TaqMan real-time PCR method, and correlated these with phenotypic antibiotic susceptibility patterns for MRSA strains collected from Gulhane Military Medical Academy Hospital (GMMAH) during 4 years study period. To our knowledge, this is the first report from Turkey of molecular SCCmec typing analysis of MRSA stains. A total of 385 clinical MRSA isolates collected in the clinical and Microbiology Laboratory at GMMAH between 2003 and 2006 were included in the study. Overall, SCCmec types-I, II, III, IV, V, nontypeable and PVL occurrence were detected in 11 (2.8%), 3 (0.8%), 316 (82.1%), 20 (5.1%), 20 (5.1%), 15 (3.9%) and 5 (1.3%) isolates, respectively. A total of 330 (85.5%) were SCCmec-I/II/III and 40 (10.3%) were SCCmec IV/V. SCCmec-I/II/III isolates were recovered more from patients with serious infections in surgical departments especially those with intensive care units than the SCCmec-IV/V isolates (chi(2) = 13.560, P < 0.001). SCCmec-I/II/III MRSA strains were predominantly recovered from blood stream (53.0%, P = 0.014), while SCCmec-IV/V strains were predominately isolated from skin and soft tissue and abscess (55.0%, P < 0.001). The PVL gene was detected in 10.0% of SCCmec-IV/V isolates in contrast to 0.3% in SCCmec-I/II/III (chi(2) = 25.164, P < 0.001). SCCmec-I/II/III MRSA strains were more resistant to clindamycin (chi(2) = 5.078, P = 0.024), amoxicillin-clavulanate (chi(2) = 84.912, P < 0.001), erythromycin (chi(2) = 4.651, P = 0.031), gentamicin (chi(2) = 24.869, P < 0.001), and rifampin (chi(2) = 18.878, P < 0.001) than SCCmec-IV/V MRSA strains. This data indicates that SCCmec-III MRSA strains that do not carry the PVL gene are the predominant MRSA strains in our hospital setting in Ankara, capital of Turkey and that SCCmec-I/II/III MRSA strains may cause serious infections in surgical departments especially those with intensive care units.

Macrolide-lincosamide-streptogramin B resistant phenotypes and genotypes for methicillin-resistant Staphylococcus aureus in Turkey, from 2003 to 2006.

Methicillin-resistant Staphylococcus aureus (MRSA) strains with inducible macrolide-lincosamide-streptogramin B (iMLS(B)) resistance phenotype may lead to clinical failure during clindamycin (CLI) therapy. The aim of this study was to determine the incidence of MLS(B) phenotypes by using D-test method and genotypes by using multiplex real-time PCR method in MRSA strains. A total of 265 MRSA strains were obtained from clinical samples from hospitalized and outpatients. Of the MRSA isolates, 225 (84.9%) were resistant to erythromycin (ERT), and 170 (64.1%) to CLI. Among the 225 ERT-resistant MRSA strains, the constitutive MLS(B) (cMLS(B)) rate was found in 49.3%, iMLS(B) in 39.1% and the M phenotype in 11.5%. Overall, ermA, ermC, ermA+ermC, msrA, ermC+msrA, and ermA+ermC+msrA genes were detected in 85 (37.7%), 60 (26.6%), 42 (18.6%), 26 (11.5%), 11 (4.8%), and 1 (0.4%) isolates, respectively. Most prevalent resistance determinant in MRSA strains was ermA, which was detected in 37.7% of the isolates. The 26 MRSA strains with M phenotype harboured only msrA gene. In conclusion, due to aware of the potential of CLI treatment failure, D-test should be performed and reported in MRSA strains in clinical laboratories. The multiplex real-time PCR method is easy to perform, fast and reliable method for the detection of MLS(B) resistance genotypes.