The High Diversity of MRSA Clones Detected in a University Hospital in Istanbul

Background: To characterize the methicillin-resistant Staphylococcus aureus (MRSA) clones present in Istanbul, 102 MRSA isolates collected during a 5-year period at the Istanbul Medical Faculty Hospital were characterized using microarray analysis and phenotypic resistance profiles.Methods: Resistance to methicillin was detected with a cefoxitin disk diffusion assay and confirmed with a MRSA-agar and MRSA detection kit. Antimicrobial susceptibility testing was performed by a disk diffusion assay and interpreted according to the 2012 guidelines of the Antibiogram Committee of the French Society for Microbiology. Decreased susceptibility to glycopeptides was confirmed using the population analysis profile-area under the curve (PAP-AUC) method. The presence of the mecA gene was detected by polymerase chain reaction. Bacterial DNA was extracted according to the manufacturer''s recommended protocol using commercial extraction kits. Strains were extensively characterized using the DNA microarray.Results: Isolates were grouped into six clonal complexes. The most frequently detected clone was the Vienna/Hungarian/Brazilian clone (ST239-MRSA-III), which accounted for 53.9% of the isolates. These isolates were resistant to multiple antibiotics, particularly penicillin, tetracycline, rifampicin, kanamycin, tobramycin, gentamicin, levofloxacin, erythromycin, lincomycin and fosfomycin. Furthermore, three isolates were detected by population analysis profile as heterogeneous vancomycin-intermediate S. aureus (hVISA). The UK-EMRSA-15 clone (ST22-MRSA-IV PVL negative) was detected in 9.8% of the isolates and was mainly susceptible to all anti-staphylococcal antibiotics. Seven isolates (6.9%) were positive for PVL genes and were assigned to the CC80-MRSA-IV clone (European CA-MRSA clone, three isolates), ST8-MRSA-IV clone (USA300 clone, two isolates, one ACME-positive) or ST22-MRSA-IV clone (“Regensburg EMRSA” clone, two isolates). All other clones were detected in one to six isolates and corresponded to well-known clones (e.g., Pediatric clone, Dublin EMRSA clone, WA MRSA-54/63, WA MRSA-1/57).Conclusions: This work highlighted both the high prevalence of ST239-MRSA-III clone and the large diversity of the other MRSA clones detected in a university hospital in Istanbul.     

Current and future treatment options for community-associated MRSA infection

Introduction: Community-associated MRSA (CA-MRSA) represents a global epidemic which beautifully encapsulates the fascinating ability of bacterial organisms to adapt quickly on an evolutionary basis to the extreme selective pressure of antibiotic exposure. In stark contrast to Healthcare-associated MRSA (HA-MRSA), it has become apparent that CA-MRSA is less straight forward of a challenge in terms of controlling its transmission, and has forced clinicians to adjust empiric management of clinical syndromes such as skin and soft tissue infection (SSTI) as well as pneumonia.

Areas covered: This review details the history and epidemiology of CA-MRSA, while covering both current and future treatment options that are and may be available to clinicians. The authors reviewed both historic and more recent literature on this ever-evolving topic.

Expert opinion: While development of new anti-MRSA agents should be encouraged, the importance of antimicrobial stewardship in the battle to stay ahead of the curve with regards to the ongoing control of the MRSA epidemic should be emphasised.     

Analysis of pulmonary heme oxygenase-1 and nitric oxide synthase alterations in experimental hepatopulmonary syndrome

BACKGROUND & AIMS: Cirrhosis and portal hypertension due to chronic common bile duct ligation reproduce the features of human hepatopulmonary syndrome, whereas portal hypertension alone due to partial portal vein ligation does not. Nitric oxide contributes to experimental hepatopulmonary syndrome, but the nitric oxide synthase forms involved remain controversial. Recently, increased pulmonary heme oxygenase-1 expression and carbon monoxide production have also been found after common bile duct ligation. Our aim was to explore the role of the heme oxygenase-1/carbon monoxide pathway in the pathogenesis of experimental hepatopulmonary syndrome. METHODS: Pulmonary heme oxygenase-1 expression and distribution were assessed in sham; 3-week partial portal vein ligation; and 1-, 2-, 3-, 4-, and 5-week common bile duct ligation animals by Northern, Western and immunohistochemical analysis relative to endothelial and inducible nitric oxide synthase levels and to hepatopulmonary syndrome development. In vivo heme oxygenase enzyme inhibition with tin protoporphyrin IX in common bile duct ligation animals was used to define effects on intrapulmonary vasodilatation and arterial blood gases. RESULTS: Heme oxygenase-1 expression in pulmonary intravascular monocytes/macrophages and arterial carboxyhemoglobin levels increased progressively from 3 to 5 weeks after common bile duct ligation relative to controls (5-week protein levels were 15.94 +/- 1.75-fold those of sham animals; P < 0.001). Inducible nitric oxide synthase increased transiently in pulmonary intravascular monocytes/macrophages in 3-week common bile duct ligation animals, whereas pulmonary microvascular endothelial nitric oxide synthase increases began at 2 weeks and correlated with the onset of hepatopulmonary syndrome. Tin protoporphyrin treatment normalized carboxyhemoglobin and improved arterial blood gases and intrapulmonary vasodilatation, reflecting partial reversal of hepatopulmonary syndrome. CONCLUSIONS: The heme oxygenase-1/carbon monoxide system is an important contributor to the progression of experimental hepatopulmonary syndrome in addition to alterations in the endothelial nitric oxide synthase/nitric oxide pathway.     

Early brain injury in premature newborns detected with magnetic resonance imaging is associated with adverse early neurodevelopmental outcome

OBJECTIVE: To determine the neurodevelopmental outcome of prematurely born newborns with magnetic resonance imaging (MRI) abnormalities. STUDY DESIGN: A total of 89 prematurely born newborns (median age 28 weeks postgestation) were studied with MRI when stable for transport to MRI (median age, 32 weeks postgestation); 50 newborns were studied again near term age (median age, 37 weeks). Neurodevelopmental outcome was determined at 18 months adjusted age (median) using the Mental Development Index (Bayley Scales Infant Development II) and a standardized neurologic exam. RESULTS: Of 86 neonatal survivors, outcome was normal in 51 (59%), borderline in 22 (26%), and abnormal in 13 (15%). Moderate/severe MRI abnormalities were common on the first (37%) and second (32%) scans. Abnormal outcome was associated with increasing severity of white matter injury, ventriculomegaly, and intraventricular hemorrhage on MRI, as well as moderate/severe abnormalities on the first (relative risk [RR] = 5.6; P = .002) and second MRI studies (RR = 5.3; P = .03). Neuromotor abnormalities on neurologic examination near term age (RR = 6.5; P = .04) and postnatal infection (RR = 4.0; P = .01) also increased the risk for abnormal neurodevelopmental outcome. CONCLUSIONS: In premature newborns, brain abnormalities are common on MRI early in life and are associated with adverse neurodevelopmental outcome.     

Magnetic resonance imaging in neonatal encephalopathy

Magnetic resonance imaging may provide invaluable information in the term born neonate with encephalopathy. However, both hardware and sequences may need adaptation from normal adult protocols. Sedation is often required to obtain good quality imaging, but anaesthesia is not necessary in this population. The perinatal history may predict the pattern of brain lesions, which, in turn, may be used to predict the neurodevelopmental outcome. Image interpretation is not easy and requires a full clinical history in addition to experience of both normal and abnormal neonatal brain appearances. Lesions evolve rapidly, and perinatally acquired leasions are at the most obvious 1-2 weeks from delivery. Early imaging in the first few days from presentation should always include diffusion-weighted sequences to identify early ischaemic change. Advanced techniques such as venography, angiography and perfusion-weighted imaging may be useful in certain situations, and serial imaging may help differentiate perinatal-acquired lesions from other pathologies.