Emergence of pan-resistance in KPC-2 carbapenemase-producing Klebsiella pneumoniae in Crete, Greece: a close call.

OBJECTIVES: KPC-2-producing Klebsiella pneumoniae (KPC-KP) ST258 has been rapidly expanding and is often associated with serious nosocomial infections. Last-line antibiotics such as colistin and tigecycline often remain the only treatment option. We describe here the evolving genetic background of KPC-KP isolates in Crete, Greece. METHODS: We tested the antibiotic susceptibility of 34 clinical isolates from patients hospitalized in 2010 and 2013-14. Whole-genome sequences of these isolates were analysed for acquired resistance genes and gene mutations. RESULTS: All KPC-KP isolates belonged to ST258 with the exception of one ST147 isolate. From 2014, 26% of isolates were non-susceptible to all antibiotics, compared with 0 of 11 isolates from 2010. Colistin resistance was associated with mutations in mgrB, which was present in 61% of isolates from 2014. Core-genome MLST analysis showed that pan-resistant isolates were closely related and appeared in two separate clusters. CONCLUSIONS: KPC-KP is rapidly evolving to pan-resistance in Crete. We identified molecular resistance markers for pan-resistant isolates and showed that core-genome MLST is a promising tool for molecular fingerprinting of KPC-KP ST258.

Time-dependent analysis of extra length of stay and mortality due to ventilator-associated pneumonia in intensive-care units of ten limited-resources countries: findings of the International Nosocomial Infection Control Consortium (INICC).

Ventilator-associated pneumonias (VAPs) are a worldwide problem that significantly increases patient morbidity, mortality, and length of stay (LoS), and their effects should be estimated to account for the timing of infection. The purpose of the study was to estimate extra LoS and mortality in an intensive-care unit (ICU) due to a VAP in a cohort of 69,248 admissions followed for 283,069 days in ICUs from 10 countries. Data were arranged according to the multi-state format. Extra LoS and increased risk of death were estimated independently in each country, and their results were combined using a random-effects meta-analysis. VAP prolonged LoS by an average of 2·03 days (95% CI 1·52-2·54 days), and increased the risk of death by 14% (95% CI 2-27). The increased risk of death due to VAP was explained by confounding with patient morbidity.

Infections by pandrug-resistant gram-negative bacteria: clinical profile, therapeutic management, and outcome in a series of 21 patients.

Clinical reports on infections by pandrug-resistant (PDR) bacteria are scarce. This observational case series study was conducted during a 2-year period at a university hospital. Patients infected by PDR gram-negative bacteria comprised the study cohort. An isolate was defined as PDR if it was resistant to all antibiotic classes available for empirical treatment. A total of 21 patients infected by PDR gram-negative bacteria were recorded. The mean APACHE II score on admission was 18.8, the mean Charlson comorbidity index was 2.9, and 20 (95.2%) patients had a history of intensive care unit hospitalization. All patients had recent exposure to multiple antibiotics (median, 6 antibiotic groups). Infections occurred at a mean of 41.5 days after admission. The mean length of stay after infection was 54.6 days and 5 (23.8%) patients died due to the infection. Treatment was mainly based on a colistin-containing regimen (47.6%) or tigecycline (33.3%). All patients treated with tigecycline had total resolution of the infection and a notably shorter length of hospital stay after infection. In conclusion, PDR gram-negative bacterial infections are associated with considerable prolongation of hospitalization and mortality, although the mortality is not as high as that expected. Tigecycline appears to be effective for the successful treatment of PDR infections

Device-associated infections in the intensive care units of Cyprus: results of the first national incidence study.

BACKGROUND: Surveillance of healthcare-associated infections (HCAIs) has become an integral part of infection control programs in several countries, especially in the intensive care unit (ICU) setting. In contrast, surveillance data on the epidemiology of ICU-acquired infections in Cyprus are limited. The aim of this study was to assess the risk of ICU-acquired infections and to identify areas for improvement in Cypriot hospitals by comparing observed incidence rates with international benchmarks and by specifying the microbiological and antibiotic resistance profiles of infecting organisms. MATERIALS AND METHODS: An active surveillance protocol was introduced in the ICUs of the four major public hospitals in Cyprus, based on the methodology of the US National Nosocomial Infections Surveillance system. RESULTS: During February to December 2007, 2,692 patients who were hospitalized in ICUs for a mean length of stay of 5 days acquired 214 infections for an overall incidence rate of 15.8 infections per 1,000 patient-days [95% confidence interval (CI): 13.8-18.1]. Bloodstream infections, pneumonias and urinary tract infections accounted for 80.4% of all infections; of these, 87.8% were device-related. Central line-associated bloodstream infection (CL-BSI) posed the greatest risk (18.6 cases per 1,000 central line-days; 95% CI 14.9-22.9), followed by ventilator-associated pneumonia (VAP) (6.4 cases per 1,000 ventilator-days; 95% CI 4.5-8.8) and catheter-associated urinary tract infection (2.8 cases per 1,000 urinary catheter-days; 95% CI 1.9-4.1). Most frequently isolated pathogens included Pseudomonas aeruginosa (21.6% of all isolates), coagulase-negative Staphylococcus (11.7%), Enterococcus spp. (11.3%) and Staphylococcus aureus (9.2%). Overall, 29.8% of P. aeruginosa isolates were imipenem-resistant and 68.2% of S. aureus were methicillin-resistant. The crude excess mortality rate associated with ICU-acquired infections was 33.2% (95% CI 24.9-41.9%) and the mean post-infection stay in the ICUs was 21.6 days (95% CI 17.0-26.2). CONCLUSION: In comparison to international benchmarks, the markedly high rate of CL-BSI, the high rate of VAP and the resistance patterns of major infecting pathogens identified in this study emphasize the need to improve current practices for appropriate use and management of invasive devices in Cypriot ICUs.

Excess mortality due to pandrug-resistant Acinetobacter baumannii infections in hospitalized patients.

BACKGROUND: Pandrug-resistant Acinetobacter baumannii (PDRAB) is increasingly being reported as a nosocomial pathogen worldwide, but determining its clinical impact is challenging. AIM: To assess the spectrum of excess mortality attributable to PDRAB infection in acute care settings. METHODS: This four-year cohort study was conducted in a tertiary-care referral hospital in Greece to estimate excess in-hospital mortality due to PDRAB infection by comparing patients infected to those colonized with PDRAB by means of competing risks survival analysis. FINDINGS: The study cohort comprised 91 patients (median age: 67 years; 77% men). For most patients, PDRAB was first isolated in the intensive care unit (ICU) (N = 51; 57%) or following ICU discharge (N = 26; 29%). Overall in-hospital mortality was 68% (95% confidence interval (CI): 57.5-77.5%). PDRAB-infected patients (N = 62; 68%) and PDRAB-colonized patients (N = 29; 32%) had similar baseline characteristics, but the absolute excess risk of 30-day mortality in infected patients compared to colonized patients was 34% (95% CI: 14-54%). Multivariable competing risks regression showed that PDRAB infection significantly increased the daily hazard of 30-day in-hospital death (cause-specific hazard ratio (csHR): 3.10; 95% CI: 1.33-7.21) while simultaneously decreasing the daily rate of discharge (csHR: 0.24; 95% CI: 0.08-0.74), thereby leading to longer hospitalization. Stronger effects were observed for bloodstream infections. CONCLUSION: New effective antimicrobials would be expected to prevent mortality in one of every three patients treated for PDRAB infection and reduce their length of hospitalization. However, available therapeutic options remain extremely limited and emphasis on preventing healthcare-associated transmission of PDRAB is ever more important.

Gram-negative bacteria as emerging pathogens affecting mortality in skin and soft tissue infections.

INTRODUCTION: Skin and soft tissue infections (SSTIs) are commonly encountered in clinical practice and mainly caused by gram-positive cocci such as S.aureus and ß-hemolytic streptococci. Complicated SSTIs involving deeper tissues often necessitate surgical intervention and occur in patients with significant comorbidities such as diabetes or immunocompromising conditions. METHODS: In this study, we retrospectively reviewed the epidemiology, clinical characteristics, microbiology, and treatment of patients admitted with SSTI during a five-year period in the Internal Medicine Department of a tertiary hospital. RESULTS: During the study period, 317 patients were recorded, with a mean age of 72.1 years. The most common underlying medical conditions were diabetes mellitus, chronic kidney disease, and heart failure. Cultures were positive in 23.3 % of cases, 62.2 % of which were polymicrobial. The most frequently isolated microorganisms were Enterococci, Escherichia coli, and Pseudomonas aeruginosa. Significant antimicrobial resistance rates were noted, in particular for gram-negative microorganisms. Mortality was higher than described in the literature and associated with age, comorbidities, and infection by gram-negative microorganisms. CONCLUSION: This study denotes the role of gram-negative bacteria in SSTI epidemiology. Therapeutic protocols regarding the empiric treatment of SSTIs should necessarily take into account the local epidemiology of isolated pathogens and antimicrobial resistance. HIPPOKRATIA 2018, 22(1): 23-28.

Mediterranean spotted fever in crete, Greece: clinical and therapeutic data of 15 consecutive patients.

The clinical, epidemiological, and therapeutic aspects of 15 patients with Mediterranean spotted fever (MSF), admitted to the Internal Medicine Department of the General Hospital of Sitia (southeastern Crete, Greece) between December 2000 and July 2003, were studied. Diagnosis was made on the basis of clinical signs and symptoms and was confirmed by serology. Of the patients studied, 67% were men and 33% women, with a median age of 52 years (range of 23-76 years). Ten cases (67%) were diagnosed between May and July. Of all the patients, 93% had a history of contact with animals, mainly with sheep (11 patients, 73%), while 53% of them had a history of tick-bite (33%), or reported the presence of ticks in their environment (20%). The typical eschar lesion (tache noir) at the tick-bite site was present in 53% of the patients, while the rash was present in 87% of them. Laboratory findings included leukopenia (47%), thrombocytopenia (54%), elevation of transaminases (80%), hyponatremia (33%), and microscopic hematuria (80%). Four patients (27%) displayed pulmonary infiltrates on chest radiography. All patients were treated with doxycycline (200 mg daily) and recovered rapidly. Renal function deteriorated in one patient with chronic renal failure, but he recovered thereafter.

Surveillance of antibiotic use in hospitals: methods, trends and targets.

A standardised antibiotic surveillance system is an essential requirement of all antibiotic control strategies. Antibiotic use can be quantified accurately using patient-level surveillance, although this is not feasible for most hospitals. Instead, population-level surveillance is a more realistic alternative for ongoing and systematic monitoring of antibiotic use. Monitoring of aggregate, ward-supply data on a monthly basis, stratification by patient care area, and analysis by the anatomical therapeutic chemical/defined daily dose (ATC/DDD) system, adjusting for bed-occupancy, provides a clear picture of antibiotic consumption density and time-trends within a hospital. When usage rates are supplemented and interpreted according to changes in hospital resource indicators, benchmarking is facilitated. This provides an efficient tool for triggering and targeting antibiotic control interventions.

Surveillance of monthly antimicrobial consumption rates stratified by patient-care area: a tool for triggering and targeting antibiotic policy changes in the hospital.

The profile and temporal trends of antimicrobial use were investigated at a university hospital. Aggregate data were analyzed according to the ATC/DDD methodology. During 1998-2002, hospital-wide antimicrobial use increased by 22%, from 86.97 to 106.24 defined daily doses per 100 bed-days [DDD/100BD]. Pooled usage rates in DDD/100BD, overall percentage increases and annual average increase rates were respectively 109.97, 35.6%, 8.1 for Medical wards, 98.21, 48.7%, 9.1 for Intensive Care Units and 74.46, 34.3%, 5.7 for Hemato-oncology wards. Surgical wards had a fairly constant usage rate (98.36). A shift towards the newer broad-spectrum antibiotics, to the detriment of the older penicillins and cephalosporins, was noted in all hospital areas. Surveillance of antimicrobial consumption using the ATC/DDD system provided a clear picture of its profile. Monthly rates over a sufficient surveillance period allowed the assessment of temporal trends. Stratification of rates according to clinical service allowed areas of concern to be specified and targeted antibiotic policy changes to be initiated.

Controversies in guidelines for the control of multidrug-resistant Gram-negative bacteria in EU countries.

The various guidelines that are available for multidrug-resistant Gram-negative bacteria are useful, and contain broad areas of agreement. However, there are also important areas of controversy between the guidelines in terms of the details of applying contact precautions, single-room isolation and active surveillance cultures, differences in the approach to environmental cleaning and disinfection, and whether or not to perform staff and patient cohorting, healthcare worker screening or patient decolonization. The evidence-base is extremely limited and further research is urgently required to inform an evidence-based approach to multidrug-resistant Gram-negative bacteria prevention and control.

Emergence of vancomycin-resistant enterococci in a tertiary hospital in Crete, Greece: a cluster of cases and prevalence study on intestinal colonisation.

The aim of this study was to investigate the clinical and epidemiological characteristics of five consecutive cases of infection with vancomycin-resistant enterococci (VRE) and the prevalence of faecal carriage of VRE among patients admitted to a 700-bed university hospital where no VRE had been isolated previously. In a 2-month period, five consecutive patients infected with VRE were detected. Three VanB+ Enterococcus faecium isolates were obtained from three patients, while two VanA+ E. faecium isolates, one VanA+ Enterococcus faecalis isolate and one VanC1+ Enterococcus gallinarum isolate were obtained from the other two patients. Of 218 faecal specimens from all hospital wards, 41 (18.8%) were found to contain VRE. Forty-two isolates of VRE were obtained, comprising one (2%) E. faecalis, 11 (27%) E. faecium, 24 (57%) E. gallinarum and six (14%) Enterococcus casseliflavus/flavescens. Four isolates carried the vanA gene, eight carried vanB, 24 carried vanC1, and six carried vanC2/C3. Use of glycopeptides, the presence of central venous catheters and renal dialysis all correlated with VRE colonisation. The prevalence rates were among the highest reported in the literature.

Evolution of aminoglycoside resistance phenotypes of four Gram-negative bacteria: an 8-year survey in a University Hospital in Greece.

In order to determine the resistance patterns and evolution trends of four common Enterobacteriaceae (Escherichia coli, Proteus spp., Klebsiella spp. and Enterobacter spp.), aminoglycoside resistance phenotypes of 8917 non-repetitive strains, isolated over an 8-year period, were analysed. Phenotypes were defined by examining the susceptibility of the strains to a panel of aminoglycosides, using disk diffusion method. A large diversity of different resistance phenotypes was encountered. A significant progressive increase in the proportions of wild-type E. coli strains was noted. Among resistant strains of Enterobacter spp. and Klebsiella spp., the incidence of phenotype KTANt (kanamycin, tobramycin, amikacin and netilmicin), indicative of AAC(6')-I production, was very high (66.7 and 46.5%, respectively). Phenotypes indicative for gentamicin-modifying enzymes as well as broad-spectrum combinations (combinations of gentamicin-modifying enzymes with AAC(6')-I) were infrequent.

Repeated multi-centre prevalence surveys of hospital-acquired infection in Greek hospitals. CICNet. Cretan Infection Control Network.

Three prevalence studies for the estimation of hospital-acquired infections (HAIs) were carried out in eight Greek hospitals on an annual basis during the years 1994-1996. The overall prevalence of HAI was 6.8, 5.5 and 5.9% for the three years, respectively. Among these, urinary tract infections ranged from 22.4 to 38.2%, lower respiratory tract infections ranged from 21.1 to 32.6%, surgical site infections ranged from 14.6 to 22.7% and bloodstream infections ranged from 9.0 to 13.2%. The prevalence of antibiotic usage among the hospitalized patients was found to be 49.3% in 1994, 47.3% in 1995 and 52.7% in 1996. Unjustified prescription of prophylactic usage was found to be the major component of these high percentages. Appropriate use of antibiotics for prophylaxis is one of the priorities of the current infection control programmes. The development of a nationwide network for the surveillance of HAIs in Greece is planned using the experience gained.

Prevalence study of hospital-acquired infections in 14 Greek hospitals: planning from the local to the national surveillance level.

A prevalence study of hospital-acquired infections (HAI) was carried out in 14 of 112 Greek hospitals (15.7%), scattered throughout Greece. Five of seven Greek university hospitals and nine regional hospitals participated in the one-day study, and 3925 hospitalized patients (10.5% of the total hospital beds in Greece) were recorded. The aim of this project was to organize a surveillance of HAI with the participation of the greatest possible number of Greek hospitals, transferring the experience from the local Cretan infection control network in an effort to create a nationwide network. Special attention was paid to recruit all Greek university hospitals in our attempt to expand the study base. Co-ordination of the participating centres, education of the infection control teams on surveillance methods, preparation of agreed definitions, and elaboration of the protocol for the collection of the data were the major objectives of this study. The difficulties, however, were limited resources and the lack of skilled personnel. The overall prevalence of HAI was found to be 9.3%. The most common HAI recorded involved lower respiratory tract infections (30.3%), followed by urinary tract infections (22.7%), bloodstream infections (15.8%), and surgical site infections (14.8%). The greatest prevalence rate was found in the adult ICU (48.4%), followed by the neonatal ICU (30.3%). The duration of hospitalization, the number of operations, the total number of used devices and invasive procedures were significantly correlated with HAI. Positive cultures were found in 51.5% of the cases. The most frequently isolated micro-organisms were: Pseudomonas aeruginosa (16.6%), Escherichia coli (10.8%), Klebsiella pneumoniae (10.3%), Staphylococcus epidermidis (8.1%) and Staphylococcus aureus (7.6%). The administration of antibiotics was also recorded. The prevalence of antibiotic use was 51.4%.

Repeated point prevalence survey of nosocomial infections in a Greek university hospital.

Two point prevalence surveys of nosocomial infections (NIs) were carried out in a Greek University hospital on an annual basis in 1998 and 1999. The overall prevalence of NIs was 9.5% and 9.1% in the first and second study, respectively. The average length of stay of patients in the hospital (ALOS) was 7.7 and 9.6 days in these two studies, respectively. Of the 97 NIs detected, the most frequent were lower respiratory tract infections (36%). Urinary tract infections, bloodstream infections, surgical site infections, and gastrointestinal infections were found in 25.8%, 19.6%, 7.2% and 4.1% of patients, respectively. The prevalence of antibiotic usage was 55.6% in 1998 and 54.1% in 1999. Empiric antibiotic therapy prevailed over prophylactic and rational therapies. These percentages are higher than those reported from other countries, emphasizing the need for rational antibiotic usage to decrease pharmacy expenses and discourage the development of resistant microorganisms. A nationwide network of surveillance of NIs in Greece is now being developed using these experiences.

Successful treatment of rhinocerebral mucormycosis with liposomal amphotericin B and surgery in two diabetic patients with renal dysfunction.

The zygomycetes are a class of fungi that can cause a variety of infections in humans. Rhinocerebral mucormycosis is a rare disease and usually affects diabetic or immunosuppressed patients. The disease progresses rapidly and is usually fatal despite aggressive surgical and medical therapy. We report the management of two cases of rhino-sinusal and orbital mucormycosis in diabetic patients on treatment with corticosteroids, and mild renal impairment, successfully treated with a combination of aggressive surgical debridement and liposomal amphotericin B.

Prevalence of self-reported myocardial infarction in a Greek sample: findings from a population-based study in an urban area (medical express 2002).

During the 1970s and 1980s, Greece was known as a country with low prevalence and incidence of coronary heart disease, compared to Western populations. However, during the past decades, the Greek population has experienced marked but uneven socio-economic development, as well as change in lifestyle habits. We assessed the prevalence of self-reported myocardial infarction (MI) in a sample of the general population, aged 20-94 years. The overall prevalence of self-reported MI was 4.1% (6.3% in men and 1.9% in women). The age-adjusted prevalence was found to be 3.6%, showing a threefold increase compared to 1980s. Age, gender (male), low educational level, obesity/overweight, hypercholesterolemia, diabetes, hypertension, smoking and origin were strongly associated with prevalence of MI. Our findings indicate that the prevalence of MI increased dramatically during the past years, reflecting the change in lifestyle habits that have gradually given way to "Western"-type diets and a more sedentary lifestyle. Therefore, the need for urgent intervention is considered essential in order to prevent a further increase of disease burden.

Endocrine function in abetalipoproteinemia: a study of a female patient of Greek origin.

AIM: To investigate the pituary, genitalia, adrenal, thyroid, parathyroid and pancreatic endocrine function of a female patient aged 37 with abetalipoproteinemia at the time of diagnosis and 5 years thereafter (after application of a modified diet). SUBJECT-METHODS: Serum concentrations of cortisol, A4, ACTH, aldosteron, renin, dehydroepiandrosterone sulfate (DHEA-5), progesterone, 17-OH progesterone, testosterone, SH13G, estradiol, luteinizing hormone, follicle stimulating hormone, T3, T4, TSH, FT3, FT4, parathormone, osteocalcin, prolactin, proinsuline, insulin, glucagon, somatomedin-C (Insulin-like Growth Factor-1, IGF-1), IG171-13P3, 25 (OH) Vitamin D3 and 1-25 (OH) 2 Vitamin D3, were measured by radioimmunoassay. Synactlien test, and 24-hour urine cortisol, were also estimated. Serum leptin estimation was carried-out using a sensitive enzymatic technique. Ionized part of serum calcium was measured by the use of a special machine (CORNING), while bone alkaline phosphatase was measured by radioimmunoassay. RESULTS: Serum progesterone and 17-OH-progesterone were reduced in both examinations. Estimation of serum progesterone performed on the 21th day of the menstrual cycle revealed again values below the lowest normal limit. Serum prolactin was increased both in rest and during movement. The levels of both, somatomedin-C (IGF-1) and leptin were below the lowest normal limit. Despite normal serum parathormone, serum-ionized calcium and 25-OH vitamin D were low, while serum bone alkaline phosphatase was increased. Serum proinsulin was increased, and serum insulin was low. Serum thyroid hormone, glucagon, parathormone, FSH, LH, ACTH, testosterone, estradiol and SH13G were normal. The hormonal profile of the patient estimated 5 years later did not differ substantially suggesting that the metabolic improvement due to the adoption of the modified diet had not any significant impact on it. CONCLUSION: Female patients with abetalipoproteinernia have reduced production of progesterone by the corpus luteum and slightly abnormal bone metabolism. The reduced production of progesterone is probably due to the low levels of serum LDL and cholesterol, while reduced serum levels of Leptin and IG17-1 are probably due to the impairment nutritional status. The adoption of a modified diet does not alter the hormonal profile significantly.