Results from the Survey of Antibiotic Resistance (SOAR) 2015-17 in Turkey: data based on CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints.

OBJECTIVES: To determine antibiotic susceptibility of Streptococcus pneumoniae and Haemophilus influenzae isolates from community-acquired respiratory tract infections (CA-RTIs) collected in 2015-17 from Turkey. METHODS: MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. RESULTS: A total of 179 S. pneumoniae and 239 H. influenzae isolates were collected. Few (27.9%) pneumococci were penicillin susceptible by CLSI oral or EUCAST low-dose breakpoints, but by EUCAST high-dose or CLSI IV breakpoints 84.4% were susceptible. The most active antibiotics (excluding penicillin IV) by CLSI breakpoints were fluoroquinolones (98.9% of isolates susceptible), ceftriaxone (83.2%), amoxicillin (78.8%) and amoxicillin/clavulanic acid (78.8%). Pneumococcal susceptibility to amoxicillin and amoxicillin/clavulanic acid was lower using EUCAST low-dose breakpoints (49.7%), although susceptibility increased when using EUCAST high-dose (57.0%-58.1%) and PK/PD (78.8%-87.7%) breakpoints. Twenty-three H. influenzae isolates were ß-lactamase positive, with 11 characterized as ß-lactamase negative and ampicillin resistant following EUCAST criteria and 5 by CLSI criteria. Generally antibiotic susceptibility was high using CLSI breakpoints: ≥92.9% for all antibiotics except ampicillin (87% by CLSI and EUCAST breakpoints) and trimethoprim/sulfamethoxazole (67.4% and 72% by CLSI and EUCAST breakpoints, respectively). Susceptibility using EUCAST breakpoints (where these are published) was similar, except for cefuroxime (oral) with 3.8% of isolates susceptible. PK/PD breakpoints indicated low susceptibility to macrolides (5.9%-10%) and cefaclor (13%). The application of different EUCAST breakpoints for low and higher doses for some of the antibiotics (amoxicillin, amoxicillin/clavulanic acid, ampicillin, penicillin, ceftriaxone, clarithromycin, erythromycin, levofloxacin and trimethoprim/sulfamethoxazole) allowed, for the first time in a SOAR study, the effect of raising the dosage on susceptibility to be quantified. CONCLUSIONS: Antibiotic susceptibility of S. pneumoniae was generally low, which is in keeping with evidence of inappropriate and high antibiotic use in Turkey. H. influenzae susceptibility was high. These data are important for empirical therapy of CA-RTIs.

Choroidal thickness measurements in children with isolated growth hormone deficiency.

PurposeThe aim of this study was to determine the choroidal thickness measurement values in cases with isolated growth hormone deficiency (IGHD), to compare them with the healthy control group by using enhanced depth imaging optical coherence tomography (EDI-OCT), and to evaluate the effect of growth hormone (GH) treatment on choroid.Patients and methodsIn this study, 23 cases who were diagnosed with IGHD as a study group and 46 healthy subjects as a control group were included. All patients and controls underwent a complete ophthalmologic examination, including an examination with EDI-OCT. Choroidal thickness (CT) was measured at the fovea and at 1000 µm intervals from the foveal center in both temporal and nasal directions.ResultsThe mean subfoveal choroidal thickness (SFCT) was 329.04±88.49 µm in the cases with IGHD and 365.35±50.48 µm in the control group (P=0.033). The mean CT at temporal 1 and 2 mm were thinner in the IGHD group than that of control group (P=0.033 and P=0.043, respectively). Nasal quadrant measurements were also found to be thinner in the IGHD cases than that of control group, but the difference was not statistically significant. We found a significant positive correlation between pubertal staging and SFCT (rs=0.607, P=0.006). There was no statistically significant difference in CT values of the study group between before and 12 months after GH treatment (P>0.05).ConclusionThis study shows patients with IGHD has a thinner CT when compared with healthy pediatric cases. GH treatment seems to be not associated with the choroidal development.

Spread of carbapenem-resistant international clones of Acinetobacter baumannii in Turkey and Azerbaijan: a collaborative study.

Epidemic clones of Acinetobacter baumannii, described as European clones I, II, and III, are associated with hospital epidemics throughout the world. We aimed to determine the molecular characteristics and genetic diversity between European clones I, II, and III from Turkey and Azerbaijan. In this study, a total of 112 bloodstream isolates of carbapenem-resistant Acinetobacter spp. were collected from 11 hospitals across Turkey and Azerbaijan. The identification of Acinetobacter spp. using conventional and sensitivity tests was performed by standard criteria. Multiplex polymerase chain reaction (PCR) was used to detect OXA carbapenemase-encoding genes (bla OXA-23-like, bla OXA-24-like, bla OXA-51-like, and bla OXA-58-like). Pulsed-field gel electrophoresis (PFGE) typing was used to investigate genetic diversity. The bla OXA-51-like gene was present in all 112 isolates, 75 (67 %) carried bla OXA-23-like, 7 (6.2 %) carried bla OXA-58-like genes, and 5 (4.5 %) carried bla OXA-24-like genes. With a 90 % similarity cut-off value, 15 clones and eight unique isolates were identified. The largest clone was cluster D, with six subtypes. Isolates from clusters D and I were widely spread in seven different geographical regions throughout Turkey. However, F cluster was found in the northern and eastern regions of Turkey. EU clone I was grouped within J cluster with three isolates found in Antalya, Istanbul, and Erzurum. EU clone II was grouped in the U cluster with 15 isolates and found in Kayseri and Diyarbakir. The bla OXA-24-like gene in carbapenemases was identified rarely in Turkey and has been reported for the first time from Azerbaijan. Furthermore, this is the first multicenter study in Turkey and Azerbaijan to identify several major clusters belonging to European clones I and II of A. baumannii.

Results from the Survey of Antibiotic Resistance (SOAR) 2011-13 in Turkey.

OBJECTIVES: Data are presented from the Survey of Antibiotic Resistance (SOAR) for respiratory tract infection pathogens collected in 2011-13 from Turkey. METHODS: MICs were determined using Etest(®). Susceptibility was assessed using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) interpretive criteria. RESULTS: Rates of antibiotic susceptibility were very low among 333 isolates of Streptococcus pneumoniae tested: penicillin 38% using CLSI (oral) and EUCAST breakpoints; erythromycin 51% using CLSI and EUCAST criteria; and cefuroxime 64.6% using CLSI and PK/PD and 46.9% using EUCAST. Of the isolates, >90% were susceptible to amoxicillin/clavulanic acid, ceftriaxone (except using EUCAST criteria: 76%), levofloxacin and high-dose intravenous penicillin. Among 339 Haemophilus influenzae isolates, 6.8% were ß-lactamase positive while 9.1% were ß-lactamase negative but ampicillin resistant (BLNAR) by CLSI (14.7% by EUCAST) criteria. Amoxicillin/clavulanic acid susceptibility was ∼90% by CLSI (with or without BLNAR adjustment, EUCAST and high-dose PK/PD) but lower, at 82.9%, by EUCAST with BLNAR adjustment. Levofloxacin susceptibility was 96% using all three breakpoints. Dramatic differences in rates of susceptibility, depending on the breakpoints used, were seen for cefaclor [94% by CLSI (86.4% BLNAR adjusted), 23% by PK/PD] and cefuroxime [97% by CLSI (89.1% BLNAR adjusted), 85% by PK/PD, 15% by EUCAST (13.0% BLNAR adjusted)]. Streptococcus pyogenes (n = 222) and Moraxella catarrhalis (n = 40) isolates remained highly susceptible to amoxicillin/clavulanic acid, cephalosporins and levofloxacin, with only erythromycin susceptibility dropping below 95% for S. pyogenes. CONCLUSIONS: Overall, amoxicillin/clavulanic acid and levofloxacin were the most active antibiotics based on all three breakpoints against these pathogens. Although susceptibility was not universally low in Turkey, high resistance rates were found in S. pneumoniae and, when using PK/PD and EUCAST breakpoints, in other respiratory pathogens.

Results from the Survey of Antibiotic Resistance (SOAR) 2002-09 in Turkey.

OBJECTIVES: To investigate changes in antibiotic susceptibility of Streptococcus pneumoniae and Haemophilus influenzae from the Survey of Antibiotic Resistance (SOAR) in community-acquired respiratory tract infections (CA-RTIs) between 2002 and 2009 in Turkey. METHODS: Previously published SOAR data were used for this analysis. MICs were determined using Etest(®) gradient strips or disc diffusion. Susceptibility against a range of antimicrobial agents was assessed using CLSI breakpoints. RESULTS: A total of 900 S. pneumoniae isolates were analysed: 2002-03 (n = 75), 2004-05 (n = 301) and 2007-09 (n = 524). Four antibiotics were tested consistently throughout and three showed a statistically significant decrease in susceptibility (P < 0.0001): penicillin (74.7% susceptible in 2002-03; 67.8% in 2004-05; and 47.2% in 2007-09); cefaclor (85.3% in 2002-03; 78.7% in 2004-05; and 53.5% in 2007-09) and clarithromycin (85.3% in 2002-03; 82.7% in 2004-05; and 61.9% in 2007-09). Susceptibility to amoxicillin/clavulanic acid did not significantly change (100% in 2002-03; 98.7% in 2004-05; and 97.7% in 2007-09). A total of 930 H. influenzae isolates were analysed: 2002-03 (n = 133), 2004-05 (n = 379) and 2007-09 (n = 418). Four antibiotics were also consistently tested: ampicillin, amoxicillin/clavulanic acid, clarithromycin and cefaclor. All showed >90% susceptibility, but only cefaclor susceptibility significantly reduced (P < 0.0001) over time (99.2% in 2002-03; 96.3% in 2004-05; and 90.4% in 2007-09). CONCLUSIONS: In S. pneumoniae from Turkey, there has been a clear statistically significant reduction in susceptibility to key antibiotics since 2002, but not to amoxicillin/clavulanic acid (or amoxicillin). However, susceptibility in H. influenzae remained stable. Continued surveillance is required to monitor future changes in antibiotic susceptibility for CA-RTI bacteria.

Multiple sclerosis and optic nerve: an analysis of retinal nerve fiber layer thickness and color Doppler imaging parameters.

PURPOSE: To compare both retinal nerve fiber layer thickness and orbital color Doppler ultrasonography parameters in patients with multiple sclerosis (MS) versus healthy controls. METHODS: This is an observational case-control study. Forty eyes from MS patients and twenty eyes from healthy volunteers were examined. Eyes were classified into three groups as group 1, eyes from MS patients with previous optic neuritis (n=20); group 2, eyes from MS patients without previous optic neuritis (n=20); and group 3, eyes from healthy controls (n=20). Following complete ophthalmologic examination and retinal nerve fiber layer thickness measurement for each group, blood flow velocities of posterior ciliary arteries, central retinal artery, ophthalmic artery, and superior ophthalmic vein were measured. Pourcelot index (resistive index), an indicator of peripheral vascular resistance, was also calculated. The statistical assessment was performed with the assistance of Pearson's Chi-square test, Mann-Whitney U-test, Kruskal-Wallis test, and Spearman's correlation test. RESULTS: The studied eyes exposed similar values in terms of intraocular pressure and central corneal thickness, implying no evidence in favor of glaucoma. All nerve fiber layer thickness values, except superior nasal quadrants, in group 1 were found to be significantly thinner than groups 2 and 3. Blood flow velocity and mean resistivity index parameters were similar in all the groups. CONCLUSIONS: In MS patients, especially with previous optic neuritis, diminished retinal nerve fiber layer thickness was observed. Contrary to several studies in the current literature, no evidence supporting potential vascular origin of ocular involvement in MS was found.

The determination of carbapenem resistance in Escherichia coli and Pneumoniae isolates related to nosocomial infections and the evaluation of risk factors.

We aimed to investigate carbapenem resistance, resistance mechanisms, risk factors and epidemiological features of Escherichia coli and Klebsiella pneumoniae strains isolated from related infections in intensive care unit (ICU) patients. Carbapenemase activity was determined by MHT, MBL Etest and enzyme extraction methods. Presence of extended-spectrum beta-lactamase (ESBL) and carbapenemase-encoding genes were investigated by PCR and sequencing. Clonal relationship of the strains was investigated by pulse field gel-electrophoresis. Acquired AmpC and Qnr were investigated by PCR. Throughout this study, 1,657 patients, and 11,483 hospitalization days were followed by active surveillance in the ICU of our 1,000-bed training hospital. Out of 108 of 196 patients, 130 E. coli- and K. pneumoniae-related nosocomial infections were determined. Minimum inhibitory concentration (MIC) levels of ertapenem were > or = 1 mg/1 in 14 K. pneumoniae and 2 E. coli strains. The highest MIC level of carbapenem was found in K. pneumoniae and E. coli strains of > or = 128 mg/l and 8 mg/l, respectively. In the carbapenem resistant strains, KPC and MBL activity were not found. On the other hand, 14 strains of K. pneumoniae and one strain of E. coli exhibited OXA-48 beta-lactamase activity. Fifty-seven percent of K. pneumoniae isolates produced OXA-48 orginating from two clones and remaining isolates originated from different clones. Thus carbapenem resistance was determined as 22% and 3% in K. pneumoniae and E. coli strains, respectively. Invasive devices, duration of total parenteral nutrition, duration of hospitalization, presence of transfusions, ESBL and multiple drug resistance were found to be risk factors for carbapenem resistance.

Resection of endobronchial hamartoma causing recurrent hemoptysis by electrocautery and cryotherapy.

BACKGROUND: Pulmonary hamartomas are rare benign tumors of the lung with an incidence of 0.025%-0.32%. Endobronchial benign lesions can cause bronchial obstruction and recurrent respiratory infections or obstructive pneumonia and recurrent hemopthysis. CASE REPORT: A 66-year-old male with recurrent hemoptysis and pneumonias for a year, was referred to our department for an endoscopic resection of an endobronchial hamartoma. Initially he refused any intervention but, as he suffered additional episodes of hemoptysis and chest infections during a year on follow up, he finally underwent interventional bronchoscopy and the lesion was cauterized using snare electrocautery probe and removed with cryoextraction. The patient has been followed for two years in our outpatient clinic, with no further problems. CONCLUSION: Endoscopic treatment with flexible bronchoscope, electrocautery and cryotherapy provides an excellent outcome. Surgical therapy, should be reserved for the hamartomas that cannot be approached through endoscopy. Hippokratia 2014; 18 (4): 355-356.

In vitro activity of avibactam (NXL104) in combination with ß-lactams against Gram-negative bacteria, including OXA-48 ß-lactamase-producing Klebsiella pneumoniae.

The objective of this study was to investigate the in vitro antibacterial activity of avibactam (formerly NXL104) in combination with imipenem, cefepime or ceftazidime against Gram-negative bacteria. Bacterial isolates included: Pseudomonas aeruginosa harbouring PER-1 ß-lactamase (n=14); Acinetobacter baumannii harbouring PER-1, OXA-51 and OXA-58 (n=20); carbapenem-non-susceptible Klebsiella pneumoniae (n=25) and Escherichia coli (n=1) harbouring OXA-48; carbapenem-non-susceptible E. coli (n=1) harbouring both IMP-1 metallo-ß-lactamase and extended-spectrum ß-lactamase (ESBL); carbapenem-non-susceptible Serratia marcescens (n=1); and carbapenem-susceptible E. coli (n=20) and K. pneumoniae isolates (n=12) with CTX-M-15 ESBL. Minimum inhibitory concentrations (MICs) of imipenem, cefepime and ceftazidime were determined in combination with 4 mg/L avibactam by the Clinical and Laboratory Standards Institute (CLSI) method on Mueller-Hinton agar. Imipenem/avibactam and ceftazidime/avibactam displayed limited potency against A. baumannii isolates, whereas cefepime/avibactam and ceftazidime/avibactam were active against P. aeruginosa. Klebsiella pneumoniae isolates with OXA-48 ß-lactamase were resistant to imipenem [MIC for 90% of the organisms (MIC(90)) ≥4 mg/L]. MIC(90) values for the combination of avibactam 4 mg/L with imipenem, cefepime and ceftazidime were in the susceptible range for all strains (MIC(90)≤0.5mg/L). All E. coli and K. pneumoniae isolates with CTX-M-15 ß-lactamase were inhibited at ≤1 mg/L for combinations with avibactam and 100% were susceptible by CLSI breakpoint criteria to imipenem, cefepime and ceftazidime. In conclusion, combinations of imipenem, cefepime and ceftazidime with avibactam may present a promising therapeutic strategy to treat infections due to K. pneumoniae with OXA-48 enzyme as well as K. pneumoniae and E. coli with CTX-M-15 enzyme.

Antimicrobial resistance in gram-negative hospital isolates: results of the Turkish HITIT-2 Surveillance Study of 2007.

Resistance rates to amikacin, ciprofloxacin, ceftazidime, cefepime, imipenem, cefoperazone/sulbactam and piperacillin/tazobactam in Escherichia coli (n= 438), Klebsiella pneumoniae (n= 444), Pseudomonas aeruginosa (n= 210) and Acinetobacter baumanni (n=200) were determined with e-test in a multicenter surveillance study (Hitit-2) in 2007. ESBL production in Escherichia coli and K. pneumoniae was investigated following the CLSI guidelines. Overall 42.0% of E.coli and 41.4% of K. pneumoniae were ESBL producers. In E. coli , resistance to imipenem was not observed, resistance to ciprofloxacin and amikacin was 58.0% and 5.5% respectively. In K. pneumoniae resistance to imipenem, ciprofloxacin and amikacin was 3.1%, 17.8% 12.4% respectively. In P. aeruginosa the lowest rate of resistance was observed with piperacillin/tazobactam (18.1%). A. baumanni isolates were highly resistant to all the antimicrobial agents, the lowest level of resistance was observed against cefoperazone/sulbactam (52.0%) followed by imipenem (55.5%). this study showed that resistance rates to antimicrobials are high in nosocomial isolates and show variations among the centers.

Hyperthyroidism and severity of orbital disease do not change the central corneal thickness in Graves' ophthalmopathy.

PURPOSE: To investigate whether the central corneal thickness (CCT) shows alterations in Graves disease and Graves ophthalmopathy (GO) cases according to the disease severity and hormonal status of the patients. METHODS: A total of 150 patients (62 male, 88 female) with Graves disease and 32 control subjects (11 male, 21 female) were included in the study. The patients were divided into six groups according to the severity of orbital involvement and thyroid hormone status. Best-corrected visual acuity, pupillary responses, color vision, biomicroscopy, CCT, intraocular pressure, and funduscopy were performed, and proptosis was measured with Hertel exophthalmometry in all patients. RESULTS: CCT values of patients with Graves disease and patients with GO with hyperthyroid or euthyroid hormonal status showed no statistical difference among themselves and versus control subjects (p>0.05). CONCLUSIONS: Hyperthyroidism or severity of orbital disease does not affect the CCT.

Hyperthyroidism and severity of orbital disease do not change the central corneal thickness in Graves'' ophthalmopathy.

PURPOSE: To investigate whether the central corneal thickness (CCT) shows alterations in Graves disease and Graves ophthalmopathy (GO) cases according to the disease severity and hormonal status of the patients. METHODS: A total of 150 patients (62 male, 88 female) with Graves disease and 32 control subjects (11 male, 21 female) were included in the study. The patients were divided into six groups according to the severity of orbital involvement and thyroid hormone status. Best-corrected visual acuity, pupillary responses, color vision, biomicroscopy, CCT, intraocular pressure, and funduscopy were performed, and proptosis was measured with Hertel exophthalmometry in all patients. RESULTS: CCT values of patients with Graves disease and patients with GO with hyperthyroid or euthyroid hormonal status showed no statistical difference among themselves and versus control subjects (p>0.05). CONCLUSIONS: Hyperthyroidism or severity of orbital disease does not affect the CCT.

PER-1- and OXA-10-like beta-lactamases in ceftazidime-resistant Pseudomonas aeruginosa isolates from intensive care unit patients in Istanbul, Turkey.

The presence of PER-1- and OXA-10-like beta-lactamases was investigated by PCR in 49 ceftazidime-resistant Pseudomonas aeruginosa isolates from patients hospitalised in the 24-bed general intensive care unit of the Istanbul Faculty of Medicine during a 12-month period between February 1999 and February 2000. The clonal relatedness of the isolates was investigated by random amplified polymorphic DNA (RAPD) analysis, and the sequences of the PER-1 and OXA genes from all isolates were determined. The rates of resistance of the isolates to imipenem, aztreonam and cefepime were 98%, 92% and 96%, respectively, and to piperacillin and piperacillin-tazobactam were 41% and 37%, respectively. Using the double-disk synergy test, 37% (18/49) of the isolates were identified as extended-spectrum beta-lactamase producers. The PER-1 gene was identified in 86% (42/49) and the OXA-10 gene in 55% (27/49) of the ceftazidime-resistant isolates. Of isolates carrying the PER-1 gene, 48% (20/42) also carried the OXA-10 gene. The respective nucleotide sequences were identical for each isolate. Sixteen RAPD patterns were detected among the PER-1-positive isolates, but 60% (25/42) of the PER-1-positive isolates belonged to two distinct patterns, while the remainder exhibited a wide clonal diversity. The results indicated that the prevalence of PER-1- and OXA-10-like beta-lactamases remains high among ceftazidime-resistant P. aeruginosa isolates in Turkey.

Relationship between quality of life and characteristics of patients hospitalised with tuberculosis.

SETTING: Atatürk Lung Diseases and Chest Surgery Hospital in Ankara, Turkey. OBJECTIVE: To determine the relationships between differences in socio-demographic and family characteristics and changes that occur within the family and social environment in hospitalised patients with tuberculosis (TB) and levels of quality of life (QOL). DESIGN: TB in-patients were interviewed using a structured questionnaire and a QOL instrument. RESULTS: Findings indicated that the patients had a lower QOL level, and that those with low levels of education, no social insurance coverage and insufficient housing conditions had lower QOL scores. Patients who experienced negative changes in family life and social environment had lower QOL levels. CONCLUSION: Diagnosis, changes in family life and social milieu, the illness process and beliefs about the illness have diverse affects on the QOL of TB patients.

Comparative in vitro activities of five quinolone antibiotics, including gemifloxacin, against clinical isolates.

The in vitro activities of ciprofloxacin, ofloxacin, norfloxacin, levofloxacin and gemifloxacin against 343 clinical isolates were compared. Gemifloxacin showed the greatest activity, with MIC90 values as low as 0.03-0.25 mg/L against Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, methicillin-susceptible Staphylococcus aureus and Klebsiella pneumoniae, while methicillin-resistant Staphylococcus aureus, Enterococcus spp., Pseudomonas spp., Acinetobacter spp., Escherichia coli and Enterobacter spp. strains exhibited low rates of susceptibility to all five fluoroquinolones.