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.     

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.     

Prognostic value of immunological profile based on CD8+ and FoxP3+ T lymphocytes in the peritumoral and intratumoral subsites for renal cell carcinoma

International Urology and Nephrology - We aimed to assess an “Immunological Profile (IP)” including CD8+ and FoxP3+ T lymphocytes for renal cell carcinoma (RCC) to evaluate its effects...     

Outcomes of Pediatric Fistulising Perianal Crohn’s Disease

Background: Perianal disease is reported more widely in pediatric Crohn patients than in the past, and has been stated as an independent modifier of the disease behavior. In this study, we aimed to analyze the clinical characteristics and outcomes of fistulising perianal Crohn’s disease (fpCD) in the pediatric age group.Methods: A total number of 149 children with an established diagnosis of inflammatory bowel disease who have been diagnosed before 18 years of age and followed in our tertiary center were revised. Clinical, endoscopic, laboratory, and radiologic data of 50 patients with CD, who had at least 18 months follow-up data, were compiled.Results: Of 50 patients, 26 (52%) were diagnosed as fpCD (38% at onset). More than half of the patients without any notable external orifices around the perianal area were diagnosed as fpCD by an magnetic resonance imaging (MRI). Pediatric fpCD patients had a higher disease activity score and platelet count, lower serum albumin level, and a higher rate of granuloma in the biopsy samples, compared with non-fistulising patients. A considerably high rate of surgical interventions (i.e., seton placement 46% and abscess drainage 15%) was performed in combination with infliximab.Conclusion: Fistulising perianal Crohn’s disease seems to be more common than previously reported in the pediatric age group. A severe course of the disease might serve as a warning for the development of fpCD. A careful physical examination and use of perianal MRI with a high index of suspicion may increase the likelihood of fistula detection, hence may change the treatment strategy.     

Enthesopathy in patients with familial Mediterranean fever: increased prevalence in M694 V variant

Enthesopathy is pathology of bony insertions of tendons, ligaments or joint capsules. It is a frequent finding in rheumatic diseases, like ankylosing spondylitis (AS) and Behçet’s disease. Musculoskeletal complaints are common in patients with familial Mediterranean fever (FMF), and these could be a clinical manifestation of enthesopathy. Hence, we investigated the possible association between FMF and enthesopathy. Fifty-six patients with FMF and 11 patients with FMF-associated spondyloarthropathy (FMFS) were enrolled. Forty-seven healthy individuals and 36 patients with AS formed the healthy and diseased control groups. Musculoskeletal complaints were meticulously questioned, and all patients underwent a detailed physical and ultrasonographic (US) examination of the lower limbs. US scorings of enthesopathy was performed according to the Glasgow Ultrasound Enthesitis Scoring System (GUESS). Demographic data, disease characteristics, MEFV genotypes and HLA B27 results were retrieved from the medical records. Patient-reported pain and physical examination findings consistent with enthesopathy were frequent in all groups with the highest prevalence in the FMFS group. Heel was the most common region affected in all patient groups. FMF patients harboring M694 V variant had higher GUESS scores compared to patients with other variants (2.78 ± 2.43 vs. 1.37 ± 1.67, p = 0.026). There was no statistically significant difference in the mean ± SD GUESS scores between healthy subjects and those FMF patients with genetic variants other than M694 V (1.38 ± 1.42 vs. 1.37 ± 1.67, p > 0.05). Enthesopathy may not be a feature of general FMF population; rather, it might be specifically associated with the presence of M694 V variant. Our results further support the previous evidence regarding M694 V mutation and spondyloarthropathy association.     

End-to-end microvascular anastomosis in the rat carotid artery using continuous horizontal mattress sutures

This paper reports a continuous horizontal mattress suture technique with advantages such as decreased time for anastomosis, minimized anastomotic leakage, eversion around the vessel edges, and other advantages which the continuous anastomosis technique has. This technique was compared with the classical interrupted and classical continuous suture techniques on a total of 59 Sprague-Dawley rat common carotid arteries: Group 1 (n = 19), interrupted suture technique; Group 2 (n = 20), standard continuous technique, and Group 3 (n = 20), continuous horizontal mattress technique. Early (30 min) and late (21 days) patency rates, anastomosis time, leakage on clamp release, oozing duration, additional sutures needed, and total number of sutures placed were statistically compared between groups. Specimens were taken at the 21st day randomly, and light microscopy (LM), scanning electron microscopy (SEM), and angiographic studies were performed. Results revealed that the continuous mattress suture technique has the advantages of providing a water-tight anastomosis with less suture materials in a shorter time, and minimal intraluminal suture material which can incite thrombosis. On the other hand, a tendency to anastomotic stricture was found to be the sole disadvantage of this technique.     

WISC-R subtest differences for male and female LD children and youth

Investigated the performance on the WISC-R of 98 learning disabled children and youth (69 males/29 females), who ranged in age from 6-3 to 13-6 to determine whether there were any significant subtest scale score differences between sexes. A 2 × 10 analysis of variance was used to analyzed these data. Differences between the individual subtest means were analyzed by using Newman Keuls test for simple effects. Results indicated that males obtained higher (but not significant) scores on the six verbal subtests. Females scored significantly higher on coding than did their counterparts. In addition, the Verbal vs. Performance IQ dichotomy did not appear as useful evidence in the diagnosis of learning disabilities. Evidence from the investigation did not indicate that a significant interaction effect existed between sexes and WISC-R subtest scores.