Evangelia-Theophano Piperaki

Treating infections caused by carbapenemase-producing Enterobacteriaceae

Carbapenemase-producing Enterobacteriaceae (CPE) have spread worldwide, causing serious infections with increasing frequency. CPE are resistant to almost all available antibiotics, complicating therapy and limiting treatment options. Mortality rates associated with CPE infections are unacceptably high, indicating that the current therapeutic approaches are inadequate and must be revised. Here, we review 20 clinical studies (including those describing the largest cohorts of CPE-infected patients) that provided the necessary information regarding isolate and patient characteristics and treatment schemes, as well as a clear assessment of outcome. The data summarized here indicate that treatment with a single in vitro active agent resulted in mortality rates not significantly different from that observed in patients treated with no active therapy, whereas combination therapy with two or more in vitro active agents was superior to monotherapy, providing a clear survival benefit (mortality rate, 27.4% vs. 38.7%; p <0.001). The lowest mortality rate (18.8%) was observed in patients treated with carbapenem-containing combinations.

Detection of cytomegalovirus, parvovirus B19 and herpes simplex viruses in cases of intrauterine fetal death: association with pathological findings.

There are previous indications that transplacental transmission of cytomegalovirus (CMV), parvovirus B19 (PB19) and herpes simplex virus types 1 and 2 (HSV‐1/2) cause fetal infections, which may lead to fetal death. In a prospective case–control study we examined the incidence of these viruses in intrauterine fetal death and their association with fetal and placenta pathological findings. Molecular assays were performed on placenta tissue extracts of 62 fetal deaths and 35 controls for the detection of CMV, PB19 and HSV‐1/2 genomes. Formalin‐fixed, paraffin‐embedded liver, spleen and placenta tissues of fetal death cases were evaluated histologically. Thirty‐four percent of placental specimens taken from intrauterine fetal deaths were positive for any of the three viruses (16%, 13%, and 5% positive for CMV, PB19, and HSV‐1/2, respectively), whereas only 6% of those taken from full term newborns were positive (P = 0.0017). No dual infection was observed. This difference was also observed when fetal deaths with a gestational age <20 weeks or a gestational age >20 weeks were compared with the controls (P = 0.025 and P = 0.0012, respectively). Intrauterine death and the control groups differed in the detection rate of CMV DNA (16% and 3%, respectively; P = 0.047), which was more pronounced in a gestational age >20 weeks (P = 0.03). Examination of the pathological findings among the PCR‐positive and PCR‐negative fetal deaths revealed that hydrops fetalis and chronic villitis were more common among the former group (P = 0.0003 and P = 0.0005, respectively). In conclusion, an association was detected between viral infection and fetal death, which was more pronounced in the advanced gestational age. Fetal hydrops and chronic villitis were evidently associated with viral DNA detection in cases of intrauterine death. J. Med. Virol. 80:1776–1782, 2008.

Evolution of multidrug-resistant Acinetobacter baumannii clonal lineages: a 10 year study in Greece (2000–09)

OBJECTIVES To analyse the evolution and genetic relatedness of Acinetobacter baumannii clonal lineages in Greece during a 10 year period. METHODS The study included 94 randomly selected A. baumannii clinical isolates recovered from 2000 to 2009 in eight tertiary Greek hospitals. Carbapenem MICs were determined by agar dilution. PCR was applied for carbapenemase genes. Isolates were typed by PFGE and tri-locus sequence typing (3LST), and 25 were also typed by multilocus sequence typing (MLST) developed by the Institut Pasteur, followed by e-Burst analysis. RESULTS All isolates were multidrug-resistant (MDR); 54 (57.4%) were non-susceptible to imipenem and/or meropenem. The bla(OXA-58) gene was identified in 51 (94.4%) carbapenem-non-susceptible and 15 (37.5%) carbapenem-susceptible isolates; other carbapenemase genes were not detected. Eight different PFGE types were identified. Sequence typing revealed previously characterized 3LST groups (1, 2, 4 and 5) and MLST types (STs) (1, 2, 15, 45 and 54) and the novel STs 85 (in two distant hospitals) and 86. Eight novel 3LST alleles were identified. Fifty-two (55.3%) isolates were assigned to 3LST group 1 and ST2 or ST45, both corresponding to international clonal complex 2 (CC2). Thirty-one (33.0%) isolates were assigned to 3LST group 2 and ST1 (CC1). From 2000 to 2004 63% of isolates belonged to 3LST group 2, but from 2005 to 2009 87.5% of isolates belonged to 3LST group 1; this shift was accompanied by an increase in carbapenem resistance from 43.5% to 64.6% of isolates. CONCLUSIONS The emergence of MDR A. baumannii in Greece was associated with CC1 and CC2, which are disseminated worldwide, often harbouring the bla(OXA-58) gene. Novel 3LST alleles and STs were also detected, underlining an evolutionary divergence in Greece.

Prevalence of Trichomonas vaginalis infection in women attending a major gynaecological hospital in Greece: a cross-sectional study

Background The prevalence of Trichomonas vaginalis is not accurately estimated, since it is not a reportable disease. Aims To assess the prevalence of T vaginalis infection in women attending a Greek gynaecological hospital and to evaluate four diagnostic methods for T vaginalis infection. Methods 255 symptomatic and 247 asymptomatic women were included in the study during 2006–07; 372 were Greek and 130 were immigrants. T vaginalis was detected in vaginal samples, using wet mount, culture in modified Diamonds medium, antigen detection and two PCR assays, targeting different regions of T vaginalis genome. Specimens were considered positive for T vaginalis, when tested positive either by culture or by both PCRs. Results 23 women (4.6%) were positive for T vaginalis. Seven of the 23 positive samples (30.4%) were only PCR-positive. Infection was more prevalent in symptomatic women (6.7%) than in asymptomatic ones (2.4%). T vaginalis was more frequently detected in immigrants (7.9%) than in Greek women (3.3%). Gardnerella vaginalis infection was significantly more frequent in women infected with T vaginalis. PCR was the most sensitive method (100%), followed by culture (69.6%), wet mount (69.6%) and latex agglutination (54.6%). Agreement between PCR and culture as well as wet mount examination was very good (κ=0.79). Conclusions The study shows a relatively low percentage of trichomoniasis in the female population living in Athens. The infection was more prevalent among immigrants, and a proportion of the infected women was asymptomatic. The tested methods had good agreement and PCR was found to improve the diagnostic yield considerably.

Dissemination of Clinical Isolates of Klebsiella oxytoca Harboring CMY-31, VIM-1, and a New OXY-2-Type Variant in the Community

ABSTRACT The aim of the present study was to investigate the epidemiological link of multidrug-resistant Klebsiella oxytoca isolates causing community-onset infections among patients attending our outpatient department and to investigate the underlying resistance mechanisms. The isolates were tested by agar dilution MICs, phenotypic carbapenemase testing, enterobacterial repetitive intergenic consensus-PCR, and pulsed-field gel electrophoresis (PFGE). PCR assays and nucleotide sequencing were employed for the identification of bla gene types and the mapping of the integron-containing metallo-β-lactamase (MBL) gene. During the study period (January 2005 to April 2007), nine broad-spectrum cephalosporin-resistant K. oxytoca clinical isolates were prospectively collected from separate outpatients with urinary tract infections. In all cases, the patients had been hospitalized or exposed to health care facilities during the preceding year. Molecular typing revealed that all isolates belonged to the same K. oxytoca clonal type, which contained five PFGE subtypes. A novel chromosomal OXY-2 β-lactamase type variant (OXY-2-9) was detected in all isolates, but no mutations in the promoter region justifying blaOXY gene overproduction were detected. In addition, all isolates harbored the plasmidic CMY-31 (LAT-4) AmpC cephalosporinase, while three of them harbored VIM-1 MBL in a class 1 integron structure. This is the first study to present the dissemination in the community of multidrug-resistant K. oxytoca isolates causing extrahospital infections.

Inflammatory bowel disease exacerbation associated with Epstein-Barr virus infection.

BACKGROUND: Epstein-Barr virus infection is associated with inflammatory bowel disease, but its role as a pathogenetic or exacerbating factor remains unclear. OBJECTIVE: The aim of this study was to evaluate the association between Epstein-Barr virus infection and inflammatory bowel disease, particularly in regard to exacerbation of disease activity. DESIGN: This was a nonrandomized crosssectional study in subgroups of patients with inflammatory bowel disease compared with a control group with noninflammatory disease. SETTINGS AND PATIENTS: Participants were patients treated for ulcerative colitis or Crohn’s disease and individuals undergoing evaluation for noninflammatory disease recruited from 2 urban adult gastrointestinal referral centers in Greece. MAIN OUTCOME MEASURES: Diagnosis of inflammatory bowel disease was based on standard clinical and endoscopic criteria. Demographic and clinical characteristics of all participants were recorded. Whole blood samples and fresh tissue samples from biopsy of intestinal sites were obtained from each participant. The presence of Epstein-Barr virus was determined by amplifying the LMP1 gene of the virus in blood and intestinal tissue samples. RESULTS: The study comprised 94 patients with inflammatory bowel disease (63 with ulcerative colitis and 31 with Crohn’s disease) and 45 controls with noninflammatory disease. Of the 94 patients, 67 (71.3%) had disease exacerbation and 27 (28.7%) were in remission. The prevalence of Epstein-Barr virus genome was significantly higher in patients than in controls for intestinal tissue (44 patients, 46.8% vs 6 controls, 13.3%; p = 0.001), but not for whole blood (24 patients, 25.5% vs 9 controls, 20%; p = 0.3). The viral genome was found significantly more frequently in intestinal samples from patients with disease exacerbation compared with patients in remission (38 patients with exacerbation, 56.7% vs 6 patients in remission, 22.2%; p = 0.001), but no significant difference was found for whole blood (18 patients with exacerbation, 26.8% vs 6 patients in remission, 22.2%; p = 0.79). Neither disease exacerbation nor the presence of virus genome was related to demographic or clinical characteristics. LIMITATIONS: The exact location of Epstein-Barr virus in the intestinal tissues could not be specified because morphological data by immunohistochemistry or in situ hybridization were not available. CONCLUSIONS: Although causality could not be determined, the significantly higher prevalence of Epstein-Barr virus in intestinal tissue from patients with inflammatory bowel disease compared with controls and in patients with exacerbation compared with patients in remission suggests a potential viral involvement in the severity of inflammatory bowel disease. These findings merit further investigation in view of a potential for usefulness of antiviral therapy against Epstein-Barr virus infection in patients with exacerbation of inflammatory bowel disease.

Malaria in Europe: emerging threat or minor nuisance?

Malaria was eradicated from Europe in the 1970s through a combination of insecticide spraying, drug therapy and environmental engineering. Since then, it has been mostly imported into the continent by international travellers and immigrants from endemic regions. Despite the substantial number of imported malaria cases and the documented presence of suitable anopheline vectors, autochthonous transmission has not been widely observed in Europe, probably as a result of early diagnosis and treatment, afforded by efficient healthcare systems. Current climatic conditions are conducive to malaria transmission in several areas of Southern Europe, and climate change might favour mosquito proliferation and parasite development, further facilitating malaria transmission. Moreover, the continuing massive influx of refugee and migrant populations from endemic areas could contribute to building up of an infectious parasite reservoir. Although the malariogenic potential of Europe is currently low, particularly in the northern and western parts of the continent, strengthening of disease awareness and maintaining robust public health infrastructures for surveillance and vector control are of the utmost importance and should be technically and financially supported to avert the possibility of malaria transmission in Europes most vulnerable areas.

A systematic classification of the vertebral artery variable origin: clinical and surgical implications

Several congenital anomalies regarding the right (RVA) and left (LVA) vertebral artery have been described. The current paper aims to perform a systematic literature review of the variable vertebral artery (VA) origin from the aortic arch (AOA) and its branches. The incidence of these variants and the ensuing AOA branching pattern are highlighted. Atypical origin cases were found more commonly unilaterally, while LVA presented the majority of the aberrancies. The LVA emersion from the AOA (3.6%) and the RVA from the right common carotid artery (RCCA) (0.14%) were the commonest origin variations. Aberrant RVA origin as last branch of the AOA is very rare. Eighteen cases (0.12%) with an aberrant right subclavian artery (ARSCA) were found. Among them, the RVA originated from the RCCA and right subclavian artery in 94.4 and 5.6%, respectively. Sporadic cases had an AOA origin bilaterally; RVA and LVA had a double origin in 0.027 and 0.11%, respectively. A dual origin was detected in 0.0069%, bilaterally. The atypical VA origin may coexist with: (i) an ARSCA, (ii) a common origin of brachiocephalic artery and left common carotid artery (the misnomer bovine arch) and (iii) a bicarotid trunk. The aberrant VA origin favors hemodynamic alterations, predisposing to cerebrovascular disorders and intracranial aneurysm formation. Detailed information of VA variants is crucial for both endovascular interventionists and diagnostic radiologists involved in the treatment of patients with cerebrovascular disease. Such information may prove useful to minimize the risk of VA injury in several procedures.