Association of doripenem resistance with OXA-type carbapenemases in Acinetobacter baumannii isolates

Objectives:

To evaluate the in vitro activity of doripenem in Acinetobacter baumannii (A. baumannii) clinical isolates that possess different OXA-type carbapenemases, and to evaluate the roles of these enzymes in the development of carbapenem resistance.

Methods:

This retrospective study was conducted with 25 A. baumannii isolates at Sakarya University Training and Research Hospital, Sakarya, Turkey from June to October 2014. Antibiotic susceptibility testing was carried out using the Vitek-2 automated system (bioMérieux, Marcy l’Etoile, France). Minimum inhibitory concentrations (MICs) were determined using Etest strips (bioMérieux, Marcy l’Etoile, France). Quantitative polymerase chain reaction was performed in a Fluorion Instrument (Iontek, Istanbul, Turkey).

Results:

Isolates were divided into 5 groups based on their susceptibility profiles and OXA-type carbapenemase positivity. Group 2 isolates whose MIC of both meropenem and doripenem are in the range of 4-32 µg/mL were negative for both bla_OXA-23 and bla_OXA-58. Group 3 isolates whose MIC of meropenem and doripenem is in the range of 4-32 µg/mL, bla_OXA-23 is positive, and bla_OXA-58 is negative. Group 5 isolates whose MIC of meropenem is >32 µg/mL, and that of doripenem is in the range of 16-32 µg/mL were positive for both bla_OXA-23 and bla_OXA-58.

Conclusion:

The bla_OXA-23 and bla_OXA-58 gene combinations may confer resistance with a much greater MIC of both meropenem and doripenem. However, the presence of bla_OXA-58 alone was not correlated with doripenem resistance.The rise of antibiotic resistance is an increasingly important threat, particularly for infections caused by Acinetobacter baumannii (A. baumannii). The use of carbapenems to treat A. baumannii infection has resulted in outbreaks of infection with carbapenem-resistant Acinetobacter spp.1 We are now faced with more problematic drug-resistant pathogens that threaten to move us into what some consider the post-antibiotic era of infectious diseases. Regardless, a potential strategy is to focus on the relation of molecular characterization of the isolates and the response to antimicrobial theraphy.2 Carbapenem resistance in Acinetobacter spp. has been ascribed to the recruitment and production of carbapenem-hydrolyzing class D β-lactamases (CHDLs), and to a lesser extent metallo-β-lactamases. In A. baumannii, the CHDLs can be intrinsic (OXA-51-like), or acquired (OXA-23-like, OXA-24-like, and OXA-58-like).3 Although these enzymes weakly hydrolyze carbapenems, they can confer strong resistance when bla_OXA genes are overexpressed, as a result of their association with mobile elements, such as ISAba1, which carries a strong promoter.4 The bla_OXA-23 gene, in association with ISAba1 is spread by A. baumannii worldwide, and is the most prevalent OXA allele in isolates from Turkey.3,5 However, the carbapenem against, which antibiotic resistance emerges according to OXA gene status is unknown. The purpose of this study was to evaluate the in vitro activity of doripenem in a collection of A. baumannii clinical isolates that possess different OXA-type carbapenemases, and to evaluate the roles of these enzymes in the development of carbapenem resistance.     

Alteration of thiol-disulfide homeostasis in workers occupationally exposed to arsenic

This study evaluates the redox state in occupationally arsenic-exposed workers (n = 71) by assessing the dynamic serum thiol-disulfide homeostasis. We determined the serum thiol-disulfide homeostasis parameters of exposed workers and controls (n = 43) using a novel automated colorimetric assay. Median urinary As and 8-isoprostane levels of exposed group were significantly higher than control group (16.40 μg/L vs 2μg/L, p < .001 and 2.28 ng/ml vs 0.54 ng/ml, p < .001, respectively). Disulfide level, disulfide/native thiol ratio, and disulfide/total thiol ratio were significantly higher in exposed group. The mean ceruloplasmine and myeloperoxidase activities of As-exposed group were significantly higher than control group (117.15 U/L vs 87.02 U/L, p = .035 and 148.53 U/L vs 97.75 U/L, p = .000, respectively). The median catalase activity did not differ in the two groups. Our findings revealed that As disrupts the thiol-disulfide homeostasis in favor of disulfide.     

The pulmonary involvement in rheumatic diseases: pulmonary effects of ankylosing spondylitis and its impact on functionality and quality of life

Rheumatic diseases are chronic inflammatory diseases which cause mild to severe functional loss and disability due to articular and extra-articular manifestations. One common form -ankylosing spondylitis (AS)- affects mainly the axial skeleton and sacroiliac joints, and certain extra-articular organs. The pulmonary involvement is a known manifestation of AS and emerges either in the form of interstitial lung disease or in the form of restricted pulmonary functions. The aim of this study is to determine the pulmonary functions in AS patients and to assess its relationship with quality of life, functionality and disease activity. Thirty-six AS patients and 34 healthy volunteers were recruited for the study. A detailed examination, pulmonary function tests, smoking inquiry and quality of life questionnaire were performed on all participants. Also patients were requested to complete functionality and disease activity indexes. The outcomes showed that 15 (41.7%) AS patients had pulmonary involvement: twelve patients with restrictive patterns, one with obstructive pattern, and two with both restrictive and obstructive patterns. Decreased forced expiratory volume in one second was associated with deteriorated functionality (p < 0.05). Decreased chest expansion was also accompanied with decreased forced vital capacity (p < 0.05). There was no statistically significant difference between the smoking and non-smoking patients in regard to disease activity, functionality and pulmonary function test variables (p > 0.05). In conclusion, the pulmonary involvement is common in AS and might have disturbed functionality and the quality of life in AS patients.     

Multiscale analysis of SRY-positive 46,XX testicular disorder of sex development: Presentation of nine cases

46,XX testicular disorder of sex development (46,XX TDSD) is a relatively rare condition characterised by the presence of testicular tissue with 46,XX karyotype. The present study aims to reveal the phenotype to genotype correlation in a series of sex-determining region Y (SRY)-positive 46,XX TDSD cases. We present the clinical findings, hormone profiles and genetic test results of six patients with SRY-positive 46,XX TDSD and give the details and follow-up findings of our three of previously published patients. All patients presented common characteristics such as azoospermia, hypergonadotropic hypogonadism and an SRY gene translocated on the terminal part of the short arm of one of the X chromosomes. Mean ± standard deviation (SD) height of the patients was 164.78 ± 8.0 cm. Five patients had decreased secondary sexual characteristics, and three patients had gynaecomastia with varying degrees. Five of the seven patients revealed a translocation between protein kinase X (PRKX) and inverted protein kinase Y (PRKY) genes, and the remaining two patients showed a translocation between the pseudoautosomal region 1 (PAR1) of X chromosome and the differential region of Y chromosome. X chromosome inactivation (XCI) analysis results demonstrated random and skewed XCI in 5 cases and 1 case, respectively. In brief, we delineate the phenotypic spectrum of patients with SRY-positive 46,XX TDSD and the underlying mechanisms of Xp;Yp translocations.     

Tissue Doppler properties of the left atrial appendage in patients with mitral valve disease

OBJECTIVE: The purpose of this study was to compare the left atrial appendage (LAA) tissue Doppler imaging (TDI) with the classical LAA function parameters in patients with mitral valve disease. METHODS: Twenty patients who had pure mitral regurgitation (group 1), 20 patients who had pure rheumatic mitral stenosis (group 2), and 20 healthy patients (group 3) were included in this study. All the cases were sinus rhythm. In order to determine the LAA functions, LAA late filling (LAALF), and late emptying (LAALE) flow velocities and LAA fractional area change (LAAFAC) were measured. LAA tissue Doppler evaluations were obtained from the PW Doppler, which was placed on the LAA lateral wall in a transverse basal short-axis approach. LAA late systolic (LAALSW) and late diastolic (LAALDW) wave velocities were obtained from TDI records transesophageal echocardiography (TEE). RESULTS: There were no significant differences among groups 1, 2, and 3 in terms of age, left ventricular (LV) ejection fraction, gender, and heart rate. No differences were observed between group 1 and the control group with respect to LAALE, LAALF, and LAAFAC. LAALE velocity and LAAFAC were significantly decreased in group 2 than group 1. LV diastolic diameter was significantly greater, whereas LAALSW and LAALDW velocities were significantly decreased in group 1 compared with group 3. There were no differences between groups 1 and 2 regarding to LAALSW and LAALDW velocities. LAALE, LAALF, LAALSW, LAALDW velocities, and LAAFAC were significantly decreased in group 2 than group 3. CONCLUSION: The TDI method may detect the LAA systolic dysfunctions, which cannot be detected using classical methods, on tissue level in patients with mitral regurgitation. In addition, the deterioration of the LAA functions at tissue level in patients with rheumatic mitral stenosis was also detected.     

Methadone detoxification: self versus physician regulation

We studied 108 heroin-dependent patients who had been "stabilized" on methadone, i.e., had no change in methadone dose for at least 2 weeks. With respect to their methadone detoxification regimen, 65 of the study patients preferred physician regulation and 43 study patients preferred self-regulation. Half of each group was randomly assigned to self- or physician regulation. Twenty-five of the 108 patients reached abstinence following a regimen which lasted 22 weeks; there was no statistically significant difference in proportion of subjects reaching abstinence from any of the four study groups. We observed no differences in treatment retention, symptom severity, frequency of urines positive for morphine or quinine, or psychosocial functioning. Study subjects preferring self-regulation had statistically significant increases in the number of dose raises. We conclude that there is no evidence to support the belief that physician regulation is superior to self-regulation in opioid detoxification regimens.     

Left Main Coronary Artery Obstruction by Dislodged Native-Valve Calculus after Transcatheter Aortic Valve Replacement

Transcatheter aortic valve replacement can be an effective, reliable treatment for severe aortic stenosis in surgically high-risk or ineligible patients. However, various sequelae like coronary artery obstruction can occur, not only in the long term, but also immediately after the procedure. We present the case of a 78-year-old woman whose left main coronary artery became obstructed with calculus 2 hours after the transfemoral implantation of an Edwards Sapien XT aortic valve. Despite percutaneous coronary intervention in that artery, the patient died. This case reminds us that early recognition of acute coronary obstruction and prompt intervention are crucial in patients with aortic stenosis who have undergone transcatheter aortic valve replacement.     

Is oxidative stress related to childhood urolithiasis?

Background

Urolithiasis is a common condition in pediatric populations in Turkey. The role of oxidative stress in renal stone formation in pediatric patients has not been reported to date. The aim of this study was to assess oxidative stress in childhood urolithiasis.

Methods

Seventy-four children diagnosed with urolithiasis and 72 healthy control subjects were enrolled in the study. Kidney stone formers were evaluated by analysis of metabolic conditions related to urolithiasis, such as hypercalciuria, hyperoxaluria, hypocitraturia and hyperuricosuria. Urine total antioxidant status (TAS), and total oxidant status (TOS) were measured, and oxidative stress index (OSI) was calculated as an indicator of the degree of oxidative stress.

Results

Among the stone formers, metabolic analyses revealed that 30 % had hypercalciuria, 45 % had hypocitraturia, 6 % had hyperoxaluria and 40 % had hyperuricosuria. Elevated levels of the renal tubular damage marker urinary N-acetyl- beta-d-glucosaminidase (NAG) was elevated in 25 % of the patient group, but microalbuminuria was not detected. Total oxidant status and total antioxidant status were significantly higher in stone formers than in the controls (p?=?0.023 and 0.004, respectively). In addition, urinary NAG was significantly correlated with TOS (r?=?0.427, p?=?0.019).

Conclusions

The results of this study show that oxidative stress may play an important role in the pathogenesis of pediatric stone formers.