Epidemiology of Mucormycosis in Greece; Results from a Nationwide Prospective Survey and Published Case Reports.

Mucormycosis has emerged as a group of severe infections mainly in immunocompromised patients. We analysed the epidemiology of mucormycosis in Greece in a multicentre, nationwide prospective survey of patients of all ages, during 2005-2022. A total of 108 cases were recorded. The annual incidence declined after 2009 and appeared stable thereafter, at 0.54 cases/million population. The most common forms were rhinocerebral (51.8%), cutaneous (32.4%), and pulmonary (11.1%). Main underlying conditions were haematologic malignancy/neutropenia (29.9%), haematopoietic stem cell transplantation (4.7%), diabetes mellitus (DM) (15.9%), other immunodeficiencies (23.4%), while 22.4% of cases involved immunocompetent individuals with cutaneous/soft-tissue infections after motor vehicle accident, surgical/iatrogenic trauma, burns, and injuries associated with natural disasters. Additionally, DM or steroid-induced DM was reported as a comorbidity in 21.5% of cases with various main conditions. Rhizopus (mostly R. arrhizus) predominated (67.1%), followed by Lichtheimia (8.5%) and Mucor (6.1%). Antifungal treatment consisted mainly of liposomal amphotericin B (86.3%), median dose 7 mg/kg/day, range 3-10 mg/kg/day, with or without posaconazole. Crude mortality was 62.8% during 2005-2008 but decreased significantly after 2009, at 34.9% (p = 0.02), with four times fewer haematological cases, fewer iatrogenic infections, and fewer cases with advanced rhinocerebral form. The increased DM prevalence should alert clinicians for timely diagnosis of mucormycosis in this patient population.

Global Cutaneous Mucormycosis: A Systematic Review.

Cutaneous mucormycosis is the third most common clinical type of mucormycosis. The signs and symptoms vary widely, and it is important to make the diagnosis as early as possible in order to achieve a better outcome. We present a systematic review of its epidemiology, clinical presentation, diagnosis, and treatment, analyzing cases published from 1958 until 2021. The review was conducted according to the PRISMA guidelines and included 693 cases from 485 articles from 46 countries. Most publications were from North America (256 cases, 36.9%) and Asia (216 cases, 31.2%). The most common risk factors were diabetes mellitus (20%) and hematological malignancies (15.7%). However, a large proportion of published cases (275, 39.6%) had no identified underlying disease. The most common mode of transmission was trauma (54%), and 108 (15.6%) cases were healthcare-associated. In this review, 291 (42.5%) patients had localized infection, and 90 (13%) had disseminated mucormycosis. In Europe, N. America and S. America, the most common genus was Rhizopus spp., while in Asia it was Apophysomyces spp. (34.7%). Treatment was performed with antifungals, mainly amphotericin B, and/or surgery. Mortality was significantly lower when both antifungals and surgery were applied (29.6%).

Management of Invasive Fungal Infections in Adult Patients with Hematological Malignancies in Greece during the Financial Crisis: Challenges and Recommendations.

There are concerns that the financial crisis in Greece negatively affected the management of invasive fungal infections (IFIs) among patients with hematological malignancies (HM). A working group (WG) was formed to explore the situation and make recommendations. A questionnaire was created and distributed to physicians caring for patients with HM, to gather information in a standardized manner on prescribing physicians, patient characteristics, availability of diagnostics, antifungal treatment practices and the conditions and particularities of Greek hospitals. A total of 141 physicians from 36 hematology units and laboratories located in 26 Greek hospitals participated. Regarding hospitalization conditions, only 56% reported that their patients were treated in isolated single or double bed rooms, 22% reported availability of HEPA filters, 47% reported construction works in progress, and an alarming 18% reported the presence of birds on open windows. Regarding diagnosis, only 31% reported availability of biomarkers for diagnosis of IFIs, 76% reported that CT scans were performed in a timely fashion, 42% reported prompt availability of broncho-alveolar lavage, and only 6% availability of therapeutic drug monitoring. Of concern, 26% of the responders reported non-availability of some antifungals. In conclusion, significant challenges exist for the optimal management of IFIs in patients with HM in Greece.

Recent Advances in the Pathogenesis of Mucormycoses.

PURPOSE: The purposes of this review are to describe the pathogenesis of mucormycosis and to address recent research advances in understanding the mechanisms of fungal invasion and dissemination. METHODS: Studies and reviews published in the PubMed and ClinicalTrials.gov databases until December 2017 that explored or reported recent advances in the understanding of the pathogenesis of mucormycosis were reviewed. FINDINGS: To cause disease, fungal spores need to evade the innate immune system and germinate, leading to angioinvasion and tissue destruction. Recent studies have found that Mucorales are able to downregulate several host defense mechanisms and have identified the specific receptors through which Mucorales attach to the endothelium, facilitating their endocytosis and subsequent angioinvasion. In addition, certain conditions found to act through various mechanisms and pathways in experimental and animal studies, such as hyperglycemia, elevated iron concentrations, and acidosis (particularly diabetic ketoacidosis), increase the virulence of the fungi and enhance their attachment to the endothelium, rendering patients with uncontrolled diabetes and patients with iron overload susceptible to mucormycosis. The role and various antifungal functions of platelets and natural killer cells are highlighted, and the potential contribution of alternative therapies, such as manipulating the innate immune host defenses with granulocyte transfusions or administration of growth factors and using the antifungal effects of calcineurin inhibitors, are presented. Finally, directions and possible implications for future research are provided. IMPLICATIONS: This article provides a comprehensive overview of research advances in the pathogenesis of infections caused by Mucorales and helps future studies develop effective treatment strategies and improve patient outcomes.

Fungal infections in patients with inflammatory bowel disease: A systematic review.

BACKGROUND: Despite reports of fungal infections in patients with inflammatory bowel disease (IBD), their clinical and microbiological characteristics remain unknown. OBJECTIVES: The aim of this systematic review was to examine all available evidence regarding fungal infections in patients with IBD. METHODS: Systematic search of PubMed (through 27 May 2017) for studies providing data on clinical, microbiological, treatment and outcome data of fungal infections in patients with IBD. The primary study outcome was to record the most common fungal species in patients with IBD. Secondary outcomes were classified into 3 categories: (i) characteristics of fungal infections; (ii) data on IBD and (iii) treatment and outcomes of fungal infections in patients with IBD. RESULTS: Fourteen studies with data on 1524 patients were included in final analysis. The most common fungal infections in patients with IBD were caused by Candida species (903 infections); the most commonly reported site of Candida infection was the gastrointestinal tract. Available evidence shows that most fungal infections occur within 12 months of IBD treatment and within 6 months when anti-TNFa agents are used. CONCLUSIONS: This systematic review thoroughly describes fungal infections in patients with IBD and provides important information for the early detection and management of these infections.

Reduction of Environmental Contamination With Multidrug-Resistant Bacteria by Copper-Alloy Coating of Surfaces in a Highly Endemic Setting.

OBJECTIVE To evaluate the efficacy of copper-coating in reducing environmental colonization in an intensive-care unit (ICU) with multidrug-resistant-organism (MDRO) endemicity DESIGN Interventional, comparative crossover trial SETTING The general ICU of Attikon University hospital in Athens, Greece PATIENTS Those admitted to ICU compartments A and B during the study period METHODS Before any intervention (phase 1), the optimum sampling method using 2 nylon swabs was validated. In phase 2, 6 copper-coated beds (ie, with coated upper, lower, and side rails) and accessories (ie, coated side table, intravenous [i.v.] pole stands, side-cart handles, and manual antiseptic dispenser cover) were introduced as follows: During phase 2a (September 2011 to February 2012), coated items were placed next to noncoated ones (controls) in both compartments A and B; during phase 2b (May 2012 to January 2013), all copper-coated items were placed in compartment A, and all noncoated ones (controls) in compartment B. Patients were randomly assigned to available beds. Environmental samples were cultured quantitatively for clinically important bacteria. Clinical and demographic data were collected from medical records. RESULTS Copper coating significantly reduced the percentage of colonized surfaces (55.6% vs 72.5%; P<.0001), the percentage of surfaces colonized by MDR gram-negative bacteria (13.8% vs 22.7%; P=.003) or by enterococci (4% vs 17%; P=.014), the total bioburden (2,858 vs 7,631 cfu/100 cm2; P=.008), and the bioburden of gram-negative isolates, specifically (261 vs 1,266 cfu/100 cm2; P=.049). This effect was more pronounced when the ratio of coated surfaces around the patient was increased (phase 2b). CONCLUSIONS Copper-coated items in an ICU setting with endemic high antimicrobial resistance reduced environmental colonization by MDROs. Infect Control Hosp Epidemiol 2017;38:765-771.

Plasmid-mediated quinolone resistance determinants among Gram-negative bacteraemia isolates: a hidden threat.

PURPOSE: The aim of the study was to investigate the prevalence of plasmid-mediated quinolone resistance (PMQR) genes in an unselected collection of bloodstream isolates recovered over an 18-month period in a laboratory affiliated to a university hospital in Athens, Greece, and to assess their impact on the in vitro activity of ciprofloxacin and levofloxacin. METHODS: Eight PMQR genes were screened by PCR and sequencing. All PMQR-positive isolates were submitted to isoelectric focusing for ß-lactamase detection, conjugation or transformation, time-kill assays, mutant prevention concentrationand inoculum effect evaluation. PCR and sequencing of gyrA and parC were performed for detection of chromosomal mutations. RESULTS: Among 96 Gram-negative isolates, 7 (7.3 %) carried one or more PMQR genes. qnrS1 was the most prevalent (5.2 %), followed by aac(6')-Ib-cr (4.2 %) and their combination (2 %). Cloning was successful for three isolates. The presence of a single PMQR determinant without any target modification was not associated with quinolone resistance with one exception, Stenotrophomonasmaltophilia carrying qnrS1, which was resistant to norfloxacin and ciprofloxacin, but in this isolate, additional mechanisms of quinolone resistance cannot be excluded. All PMQR-positive isolates showed a significant inoculum effect. The mutant prevention concentrations of ciprofloxacin against the quinolone-susceptible clinical isolates ranged from 0.38 to 32 mg l-1 and those of levofloxacin from 1 to 32 mg l-1. CONCLUSIONS: PMQRs compromised the bactericidal activity of ciprofloxacin and levofloxacin when expressed in Enterobactercloacae, S. maltophilia or Klebsiellapneumoniae and when more than one co-existed. PMQR determinants represent an unrecognized threat, capable to compromise the in vitro activity of quinolones if expressed in a favourable genetic environment and to favour selection of resistant mutants by widening the mutant selection window of these agents.

Diagnostic value of a semi-nested PCR for the diagnosis of mucormycosis and aspergillosis from paraffin-embedded tissue: A single center experience.

OBJECTIVE: The main aim of our study was to investigate the diagnostic value of a molecular method for the diagnosis of mucormycosis and aspergillosis from formalin-fixed and paraffin-embedded (FFPE) tissues. METHODS: A retrospective chart review identified all cases with histology reports mentioning the presence of fungi with morphological characteristics of either Aspergillus or mucormycetes, for the period 2005-2012. Paraffin blocks were retrieved from the archives of the Department of Pathology. A semi-nested PCR specific for the detection of mucormycetes and Aspergillus species was applied in FFPE tissue from the above blocks. Results were compared with those of histological (gold standard) and microbiological methods. RESULTS: Twenty cases with fungal hyphae in tissue were revealed. Mucormycetes were detected in 9 cases (45%) by PCR, in only 4 of which culture was available. Species of Aspergillus were detected in 8 cases (40%) by PCR, two of which were co-infection with mucormycetes. Five patients had other fungi, non-detectable with this specific PCR. At least one sample per patient was positive by PCR. Seven out of 30 samples tested overall were false negative. The calculated sensitivity of this method in our setting was 79.3% (95% CI: 60.3-91.9%); specificity was 100%. CONCLUSIONS: The specific PCR used appears to be an easy and useful tool for the prompt and accurate diagnosis of mucormycosis and aspergillosis, in combination with histology and direct examination. Mucormycosis was more frequent than aspergillosis during the study period, highlighting the importance of continuous epidemiological surveillance of these serious infections.

'Prostate Abscess' as the Initial Manifestation of Granulomatosis with Polyangiitis (Wegener's Granulomatosis).

Prostatic involvement in granulomatosis with polyangiitis (GWP), formerly known as Wegener's granulomatosis, is rare, mostly arising in the context of systemic involvement. Prostatic involvement as the first manifestation of this systemic disease is exceptionally rare. We hereby present the case of a 41-year-old male patient who underwent transurethral prostate resection for what was initially diagnosed as suppurative, focally necrotizing prostatitis. Prolonged postoperative fever that did not respond to various treatments, as well as the subsequent appearance of a left pleural effusion, a left upper pulmonary lobe lesion and cutaneous nodules, led to a reevaluation of histological slides which, along with the determination of serum c-ANCA/anti-PR3 antibody levels, established the diagnosis of GWP. Physicians, and especially urologists and infectious diseases specialists, should be aware of this rare association and consider GWP in the event of nonresolving prostatitis, especially when characteristic symptoms from other systems appear.

The association between colonization with carbapenemase-producing enterobacteriaceae and overall ICU mortality: an observational cohort study.

OBJECTIVES: Infections caused by carbapenemase-producing Enterobacteriaceae are increasing worldwide, especially in ICUs, and have been associated with high mortality rates. However, unequivocally demonstrating causality of such infections to death is difficult in critically ill patients because of potential confounding and competing events. Here, we quantified the effects of carbapenemase-producing Enterobacteriaceae carriage on patient outcome in two Greek ICUs with carbapenemase-producing Enterobacteriaceae endemicity. DESIGN: Observational cohort study. SETTING: Two ICUs with carbapenemase-producing Enterobacteriaceae endemicity. PATIENTS: Patients admitted to the ICU with an expected length of ICU stay of at least 3 days were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Carbapenemase-producing Enterobacteriaceae colonization was established through screening in perineum swabs obtained at admission and twice weekly and inoculated on chromogenic plates. Detection of carbapenemases was performed phenotypically, with confirmation by polymerase chain reaction. Risk factors for ICU mortality were evaluated using cause-specific hazard ratios and subdistribution hazard ratios, with carbapenemase-producing Enterobacteriaceae colonization as time-varying covariate. One thousand seven patients were included, 36 (3.6%) were colonized at admission, and 96 (9.5%) acquired carbapenemase-producing Enterobacteriaceae colonization during ICU stay, and 301 (29.9%) died in ICU. Of 132 carbapenemase-producing Enterobacteriaceae isolates, 125 (94.7%) were Klebsiella pneumoniae and 74 harbored K. pneumoniae carbapenemase (56.1%), 54 metallo-ß-lactamase (40.9%), and four both (3.0%). Carbapenemase-producing Enterobacteriaceae colonization was associated with a statistically significant increase of the subdistribution hazard ratio for ICU mortality (subdistribution hazard ratio=1.79; 95% CI, 1.31-2.43), not explained by an increased daily hazard of dying (cause-specific hazard ratio for death=1.02; 95% CI, 0.74-1.41), but by an increased length of stay (cause-specific hazard ratio for discharge alive=0.73; 95% CI, 0.51-0.94). Other risk factors in the subdistribution hazard model were Acute Physiology and Chronic Health Evaluation II score (subdistribution hazard ratio=1.13; 95% CI, 1.11-1.15), female gender (subdistribution hazard ratio=1.29; 95% CI, 1.02-1.62), presence of solid tumor (subdistribution hazard ratio=1.54; 95% CI, 1.15-2.06), hematopoietic malignancy (subdistribution hazard ratio=1.61; 95% CI, 1.04-2.51), and immunodeficiency (subdistribution hazard ratio=1.59; 95% CI, 1.11-2.27). CONCLUSIONS: Patients colonized with carbapenemase-producing Enterobacteriaceae have on average a 1.79 times higher hazard of dying in ICU than noncolonized patients, primarily because of an increased length of stay.

Development of new strategies for early diagnosis of mucormycosis from bench to bedside.

Early diagnosis and initiation of amphotericin B (AmB) for treatment of mucormycosis increases survival from approximately 40% to 80%. The central objective of a new study of the European Confederation of Medical Mycology (ECMM) and the International Society for Human and Animal Mycology (ISHAM) Zygomycosis Working Group is to improve the clinical and laboratory diagnosis of mucormycosis. The diagnostic tools generated from this study may help to significantly improve survival from mucormycosis worldwide. The study has three major objectives: to conduct a prospective international registration of patients with mucormycosis using a well-established global network of centres; to construct a predictive risk model for patients at risk for mucormycosis; and to establish an international archive of specimens of tissues, fluids, and organisms linked from the patients enrolled into the registry that will be used for development of leading edge molecular, proteomic, metabolic and antigenic systems for mucormycosis.

Rhodotorula mucilaginosa associacted meningitis: A subacute entity with high mortality. Case report and review.

A fatal case of meningitis due to Rhodotorula mucilaginosa in a 28 year-old HIV-negative male with a history of Hodgkin lymphoma who underwent salvage chemotherapy is presented. Reviewing the literature we identified 13 cases with central nervous system infection due Rhodotorula spp. The disease usually occurs in HIV negative immunosupressed middle-aged males. It takes the form of subacute or chronic meningitis accompanied by fever with an overall mortality of 46.2% despite antifungal therapy.

Breakthrough candidaemia caused by phenotypically susceptible Candida spp. in patients with haematological malignancies does not correlate with established interpretive breakpoints.

In a study of 27,864 patients with haematological malignancies, 40 patients with candidaemia were identified, among whom 21 developed candidaemia while receiving systemic antifungal therapy [breakthrough candidaemia (BTC)]. Demographic, clinical, microbiological and molecular features of these episodes were analysed. Compared with 19 patients with de novo candidaemia, patients with BTC were more likely to have neutropenia (81% vs. 63%), longer median duration of neutropenia (27 days vs. 15 days), hypogammaglobulinaemia (62% vs. 37%) and central venous catheters (CVCs) (86% vs. 68%). The median duration of prior antifungal exposure was 46 days (range 3-108 days). Among the 18 available Candida spp. isolates, 15 (83%) were phenotypically susceptible to the antifungal agent that the patient was receiving. Emergence of resistance was the mechanism leading to BTC in three cases of patients receiving echinocandins. Other possible mechanisms of BTC were (i) elevated (≥2) minimum lethal concentration/minimum inhibitory concentration (MLC/MIC) ratio (reduced ability for a fungicidal agent to kill a fungal pathogen) in all patients receiving amphotericin B and (ii) elevated MLC/MIC ratios in all Candida parapsilosis isolates with MICs≤1 µg/mL to echinocandins. DNA sequencing of the hotspot 1 region of the fks1 and fks2 genes in seven different isolates of C. parapsilosis group demonstrated P660A in Fks1 but no polymorphisms in fks2. In conclusion, mechanisms for BTC in the setting of prolonged neutropenia may be host-based (hypogammaglobulinaemia and CVC) and pathogen-based. CLSI interpretive breakpoints do not reliably predict BTC in patients with haematological malignancies and warrant further investigation.

Prescription of antibiotics and knowledge about antibiotic costs among physicians working in tertiary-care hospitals.

The objective of this study is to investigate antibiotic prescription practices among hospital-based physicians in Greece, using the 2007 national guidelines as the golden standard. A total of 168 physicians participated. Compliance rate with the first-line antibiotic treatment recommended by the national guidelines was 65·5% for acute bacterial sinusitis; 24% for acute uncomplicated cystitis; 36·4% for an acute febrile diarrheic syndrome; 38% for an afebrile adult with chronic obstructive pulmonary disease and non-productive cough of 7 days duration; 23·2% for streptococcal pharyngotonsillitis; 55·1% for a surgically sutured, dirty wound; and 48·2% for community-acquired pneumonia. The total mean rate of compliance with the first recommended antibiotic was 41·2%.

Colistin/daptomycin: an unconventional antimicrobial combination synergistic in vitro against multidrug-resistant Acinetobacter baumannii.

The in vitro activity of the combination colistin/daptomycin was evaluated against multidrug-resistant Acinetobacter baumannii clinical isolates. Clonal relationships were assessed by pulsed-field gel electrophoresis. The following synergy studies were undertaken: (i) daptomycin MICs were determined by E-test on Mueller-Hinton agar plates supplemented with a subinhibitory concentration of colistin; and (ii) time-kill methodology using tubes containing an inoculum of 5×10(5)CFU/mL and subinhibitory concentrations of each antibiotic alone or in combination subcultured at 0, 5 and 24h for colony counting. Synergy was defined as ≥2log10CFU/mL decrease of viable colonies compared with colistin alone. Ten colistin-susceptible and four colistin-resistant A. baumannii isolates were tested. Isolates were assigned to nine different clonal types. Enhanced in vitro activity of the combination was detected only against colistin-susceptible isolates; using plates supplemented with colistin, the daptomycin MIC was reduced by 4- to 128-fold. From a total of 30 isolate-concentration combinations in time-kill studies, a synergistic interaction was detected in 16 (53.3%). The combination exhibited synergy against 8 and 12 of these combinations at 5h and 24h, respectively. No antagonism was detected. Colistin alone was bactericidal against two colistin-susceptible isolates at 24h, whereas the combination was bactericidal against 9 colistin-susceptible isolates at 24h. Against all colistin-resistant isolates, the combination exhibited a static effect and indifference in time-kill studies. Potent in vitro synergistic interactions between colistin and daptomycin provide evidence that this unorthodox combination may be beneficial in the treatment of colistin-susceptible multidrug-resistant A. baumannii.

Interventions to reduce colonisation and transmission of antimicrobial-resistant bacteria in intensive care units: an interrupted time series study and cluster randomised trial.

BACKGROUND: Intensive care units (ICUs) are high-risk areas for transmission of antimicrobial-resistant bacteria, but no controlled study has tested the effect of rapid screening and isolation of carriers on transmission in settings with best-standard precautions. We assessed interventions to reduce colonisation and transmission of antimicrobial-resistant bacteria in European ICUs. METHODS: We did this study in three phases at 13 ICUs. After a 6 month baseline period (phase 1), we did an interrupted time series study of universal chlorhexidine body-washing combined with hand hygiene improvement for 6 months (phase 2), followed by a 12-15 month cluster randomised trial (phase 3). ICUs were randomly assigned by computer generated randomisation schedule to either conventional screening (chromogenic screening for meticillin-resistant Staphylococcus aureus [MRSA] and vancomycin-resistant enterococci [VRE]) or rapid screening (PCR testing for MRSA and VRE and chromogenic screening for highly resistant Enterobacteriaceae [HRE]); with contact precautions for identified carriers. The primary outcome was acquisition of resistant bacteria per 100 patient-days at risk, for which we calculated step changes and changes in trends after the introduction of each intervention. We assessed acquisition by microbiological surveillance and analysed it with a multilevel Poisson segmented regression model. We compared screening groups with a likelihood ratio test that combined step changes and changes to trend. This study is registered with ClinicalTrials.gov, number NCT00976638. FINDINGS: Seven ICUs were assigned to rapid screening and six to conventional screening. Mean hand hygiene compliance improved from 52% in phase 1 to 69% in phase 2, and 77% in phase 3. Median proportions of patients receiving chlorhexidine body-washing increased from 0% to 100% at the start of phase 2. For trends in acquisition of antimicrobial-resistant bacteria, weekly incidence rate ratio (IRR) was 0·976 (0·954-0·999) for phase 2 and 1·015 (0·998-1·032) for phase 3. For step changes, weekly IRR was 0·955 (0·676-1·348) for phase 2 and 0·634 (0·349-1·153) for phase 3. The decrease in trend in phase 2 was largely caused by changes in acquisition of MRSA (weekly IRR 0·925, 95% CI 0·890-0·962). Acquisition was lower in the conventional screening group than in the rapid screening group, but did not differ significantly (p=0·06). INTERPRETATION: Improved hand hygiene plus unit-wide chlorhexidine body-washing reduced acquisition of antimicrobial-resistant bacteria, particularly MRSA. In the context of a sustained high level of compliance to hand hygiene and chlorhexidine bathings, screening and isolation of carriers do not reduce acquisition rates of multidrug-resistant bacteria, whether or not screening is done with rapid testing or conventional testing. FUNDING: European Commission.

Action Plan to combat infections due to carbapenem-resistant, Gram-negative pathogens in acute-care hospitals in Greece.

The prevalence of carbapenem-resistant pathogens (CRPs) has increased worldwide. Given the importance of CRPs for public health and the high rates of carbapenem resistance observed in Greece, the Hellenic Center for Disease Control and Prevention (HCDCP) under the auspices of the Ministry of Health has undertaken initiatives to develop an Action Plan (i) to estimate the burden of CRP infections in acute-care hospitals in Greece and (ii) to implement infection control measures to limit the intrahospital transmission of these organisms. Starting in November 2010, specific infections caused by CRPs were reported to the HCDCP weekly. Results showed that CRP infections constitute a significant public health problem in acute-care hospitals in this country, with a mean incidence of 0.48 per 1000 patient-days and a crude 28-day mortality rate of 34.4%. The second phase of the Action Plan consists of systemic evaluation for adherence to an infection control bundle including enhanced standard infection control practices, separation of carriers and infected patients from non-carriers, and strict implementation of contact precautions. Communication between hospitals and public health authorities has been established to facilitate rapid notification and feedback.

Risk factors for community-associated methicillin-resistant Staphylococcus aureus colonisation in a large metropolitan area in Greece: An epidemiological study using two case definitions.

The aim of this study was to evaluate the epidemiology and characteristics and to identify modifiable risk factors for community-associated (CA) MRSA colonisation in a region with high prevalence. A large patient population (n=2280) from two tertiary care centres in Athens (Greece) was evaluated. Demographics and potential risk factors for CA-MRSA colonisation were recorded prospectively. Presence of the Panton-Valentine Leukocidin (PVL) toxin and mecA gene was determined in all MRSA isolates. Two definitions for CA-MRSA were applied. Univariate and multivariate analyses to identify predictors of previously unknown CA-MRSA colonisation were performed. In total, 120 (5.3%) MRSA carriers were identified; in 67 the isolates were classified as CA-MRSA using criteria based on the CDC definition, compared with 35 based on a definition including PVL toxin positivity. Factors significantly associated with previously unknown CA-MRSA carriage (CDC definition) included being a child or adolescent (OR=3.6, 95% CI 1.5-8.6), belonging to the family of an index case (OR=2.4, 95% CI 1.2-4.8), and presence of any co-morbidity (OR=1.7, 95% CI 1.04-2.8) or chronic skin disease (OR=3.6, 95% CI=2.2-6.1). In multivariate analysis, presence of any co-morbidity was the only significant predictor (OR=4.9, 95% CI 1.07-22.5; P=0.04). No easily modifiable risk factor for previously unknown CA-MRSA colonisation was identified. The CDC-based epidemiological definition for CA-MRSA appears to be more sensitive in detection of CA-MRSA colonisation than a purely molecular definition based on presence of the PVL gene.

Acute microcirculatory effects of medium frequency versus high frequency neuromuscular electrical stimulation in critically ill patients - a pilot study.

BACKGROUND: Intensive care unit-acquired weakness (ICUAW) is a common complication, associated with significant morbidity. Neuromuscular electrical stimulation (NMES) has shown promise for prevention. NMES acutely affects skeletal muscle microcirculation; such effects could mediate the favorable outcomes. However, optimal current characteristics have not been defined. This study aimed to compare the effects on muscle microcirculation of a single NMES session using medium and high frequency currents. METHODS: ICU patients with systemic inflammatory response syndrome (SIRS) or sepsis of three to five days duration and patients with ICUAW were studied. A single 30-minute NMES session was applied to the lower limbs bilaterally using current of increasing intensity. Patients were randomly assigned to either the HF (75 Hz, pulse 400 µs, cycle 5 seconds on - 21 seconds off) or the MF (45 Hz, pulse 400 µs, cycle 5 seconds on - 12 seconds off) protocol. Peripheral microcirculation was monitored at the thenar eminence using near-infrared spectroscopy (NIRS) to obtain tissue O2 saturation (StO2); a vascular occlusion test was applied before and after the session. Local microcirculation of the vastus lateralis was also monitored using NIRS. RESULTS: Thirty-one patients were randomized. In the HF protocol (17 patients), peripheral microcirculatory parameters were: thenar O2 consumption rate (%/minute) from 8.6 ± 2.2 to 9.9 ± 5.1 (P = 0.08), endothelial reactivity (%/second) from 2.7 ± 1.4 to 3.2 ± 1.9 (P = 0.04), vascular reserve (seconds) from 160 ± 55 to 145 ± 49 (P = 0.03). In the MF protocol: thenar O2 consumption rate (%/minute) from 8.8 ± 3.8 to 9.9 ± 3.6 (P = 0.07), endothelial reactivity (%/second) from 2.5 ± 1.4 to 3.1 ± 1.7 (P = 0.03), vascular reserve (seconds) from 163 ± 37 to 144 ± 33 (P = 0.001). Both protocols showed a similar effect. In the vastus lateralis, average muscle O2 consumption rate was 61 ± 9%/minute during the HF protocol versus 69 ± 23%/minute during the MF protocol (P = 0.5). The minimum amplitude in StO2 was 5 ± 4 units with the HF protocol versus 7 ± 4 units with the MF protocol (P = 0.3). Post-exercise, StO2 increased by 6 ± 7 units with the HF protocol versus 5 ± 4 units with the MF protocol (P = 0.6). These changes correlated well with contraction strength. CONCLUSIONS: A single NMES session affected local and systemic skeletal muscle microcirculation. Medium and high frequency currents were equally effective.

Genetic basis of aminoglycoside resistance following changes in aminoglycoside prescription patterns.

Aminoglycosides (AG) offer an important therapeutic option for the treatment of infections caused by multiresistant Enterobacteriaceae. We observed a change in AG usage patterns in our institution between 1997 and 2006, namely a reduction in use of all AG except amikacin. We studied the changes in AG susceptibility rates in these time periods and correlated with prevalence of different molecular resistance mechanisms. Enterobacteriaceae isolated from blood cultures from 1997 and 2006 were studied. Susceptibilities to AG were determined with the disk diffusion method. PCR was used to detect genes encoding AG-modifying enzymes and methylases. Gentamicin resistance rates dropped from 14·5 to 8·8%, whereas resistance rates to other AG remained unchanged. The AAC(6')-I+AAC(3)-I combination was more common in 1997, whereas AAC(6')-I was the most common mechanism in 2006. Reduction in gentamicin use may preserve the usefulness of this agent against severe infections by multiresistant bacteria such as carbapenemase-producing Enterobacteriaceae.