Investigation of the relationship between IL17A, IL17F and ILR1N polymorphisms and COVID-19 severity: The predictive role of IL17A rs2275913 polymorphism in the clinical course of COVID-19.

Coronavirus disease 2019 (COVID-19) is an infectious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the mortality rate of the disease has been relatively under control as of 2022, more than 15 million confirmed COVID-19 cases have been detected in Turkey to date, causing more than 100,000 deaths. The clinical manifestation of the disease varies widely, ranging from asymptomatic to acute respiratory distress syndrome causing death. The immune response mechanisms have an important impact on the fine adjustment between healing and enhanced tissue damage. This study aims to investigate the relationship between the variants of the interleukin 1 receptor antagonist (IL1RN), interleukin 17A (IL17A), and interleukin 17F (IL17F) genes and COVID-19 severity. The study population comprised 202 confirmed COVID-19 cases divided into three groups according to severity. The IL1RN variable number of a tandem repeat (VNTR) polymorphism was genotyped by polymerase chain reaction (PCR), and IL17A rs2275913, IL17F rs763780 and rs2397084 polymorphisms were genotyped by the PCR-based restriction fragment length polymorphism method. Statistical analysis revealed a significant association between IL17A rs2275913 variant and COVID-19 severity. The AA genotype and the A allele of IL17A rs2275913 were found significant in the severe group. Additionally, we found a significant relationship between haplotype frequency distributions and severity of COVID-19 for the IL17F rs763780/rs2397084 (p = 0.044) and a combination of IL17F rs763780/rs2397084/ IL17A rs2275913 (p = 0.04). The CG and CGA haplotype frequencies were significantly higher in the severe group. IL17A rs2275913, IL17F rs763780 and rs2397084 variants appear to have important effects on the immune response in COVID-19. In conclusion, variants of IL17A rs2275913, IL17F rs763780 and rs2397084 may be the predictive markers for the clinical course and potential immunomodulatory treatment options in COVID-19, a disease that has placed a significant burden on our country.

Polymorphisms of ACE (I/D) and ACE2 receptor gene (Rs2106809, Rs2285666) are not related to the clinical course of COVID-19: A case study.

Coronavirus disease 2019 (COVID-19) is an infectious disease, and the reason behind the currently ongoing pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Angiotensin-converting enzyme (ACE2) has been recognized as the specific receptor of the SARS-CoV-2 virus. Although the possible effect of ACE2 gene polymorphism remains unknown, human ACE2 receptor expression influences SARS-CoV-2 susceptibility and COVID-19 disease outcome. In this study, we aimed to investigate the relationship between ACE gene I/D polymorphism, ACE2 receptor gene polymorphism, and COVID-19 severity. ACE gene insertion/deletion (I/D) polymorphism and ACE2 receptor gene rs2106809 and rs2285666 polymorphisms were determined using polymerase chain reaction (PCR) and PCR-based restriction fragment length polymorphism methods, respectively, in 155 COVID-19 patients who were divided into three groups (mild, moderate, and severe) according to clinical symptoms. However, the distribution of genotype and allele frequencies of ACE gene I/D, ACE2 receptor gene rs2106809, and rs2285666 polymorphisms were not statistically significant in all groups. In conclusion, in the study population, ACE gene I/D, ACE2 receptor gene rs2106809, and rs2285666 polymorphisms were not associated with the severity of COVID-19 infection. Although ACE2 receptor gene expression may affect the susceptibility to COVID-19, there is no existing evidence that the ACE or ACE2 gene polymorphisms are directly associated with COVID-19 severity. Interindividual differences in COVID-19 severity might be related to epigenetic mechanisms of ACE2 receptor gene expression or variations in other genes suggested to play a critical role in COVID-19 pathogenesis such as pro-inflammatory cytokines and coagulation indicators.

Platelet and mean platelet volume kinetics in adult patients with sepsis.

The aims of this study were to evaluate the kinetics of platelet counts and mean platelet volume (MPV) in adults with sepsis and to determine whether the responses are infection-specific. This retrospective cohort study included patients admitted to a tertiary-care teaching hospital with microbiologically proven nosocomial sepsis between January 2006 and January 2011. Platelet counts and MPV measurements were examined daily for 5 days after the onset of sepsis. During the study period, 151 of the 214 sepsis episodes were associated with thrombocytopenia. Gram-positive microorganisms were the most frequently isolated. The decrease in platelet counts was statistically significant for the first 3 days of sepsis in Gram-positive septic patients, for 4 days in Gram-negative septic patients and for all 5 days in fungal septic patients (p < 0.001). The increase in MPV values was statistically significant for the first 3 days of sepsis in Gram-positive septic patients and for all 5 days in the other groups (p < 0.001). We conclude that fungal sepsis has a stronger association with thrombocytopenia and increased MPV.

The 3'UTR region of the DNA repair gene PARP-1 May increase the severity of COVID-19 by altering the binding of antiviral miRNAs.

COVID-19 may cause the release of systemic inflammatory cytokines resulting in severe inflammation. PARP-1 has been identified as a nuclear enzyme that is activated by DNA strand breaks. It has been suggested that PARP-1 has a role in the cytokine storm shown as a cause of mortality in COVID-19, and its inhibition may adversely affect the replication of SARS -CoV-2. We aimed to investigate the relationship between PARP-1 gene polymorphisms and the clinical severity of COVID-19. rs8679 TT genotype was found to increase with the COVID-19 disease severity. The 3'UTR polymorphism rs8679 may cause PARP-1 activity as a result of viral replication increase by changing the binding site of antiviral or anti-inflammatory miRNAs. PARP-1 may affect the severity of COVID-19 by cytokine release and maybe a possible treatment target.

Inadequate treatment of ventilator-associated and hospital-acquired pneumonia: risk factors and impact on outcomes.

BACKGROUND: Initial antimicrobial therapy (AB) is an important determinant of clinical outcome in patients with severe infections as pneumonia, however well-conducted studies regarding prognostic impact of inadequate initial AB in patients who are not undergoing mechanical ventilation (MV) are lacking. In this study we aimed to identify the risk factors for inadequate initial AB and to determine its subsequent impact on outcomes in both ventilator associated pneumonia (VAP) and hospital acquired pneumonia (HAP). METHODS: We retrospectively studied the accuracy of initial AB in patients with pneumonia in a university hospital in Turkey. A total of 218 patients with HAP and 130 patients with VAP were included. For each patient clinical, radiological and microbiological data were collected. Stepwise multivariate logistic regression analysis was used for risk factor analysis. Survival analysis was performed by using Kaplan-Meier method with Log-rank test. RESULTS: Sixty six percent of patients in VAP group and 41.3% of patients in HAP group received inadequate initial AB. Multiple logistic regression analysis revealed that the risk factors for inadequate initial AB in HAP patients were; late-onset HAP (OR = 2.35 (95% CI, 1.05-5.22; p = 0.037) and APACHE II score at onset of HAP (OR = 1.06 (95% CI, 1.01-1.12); p = 0.018). In VAP patients; antibiotic usage in the previous three months (OR = 3.16 (95% CI, 1.27-7.81); p = 0.013) and admission to a surgical unit (OR = 2.9 (95% CI, 1.17-7.19); p = 0.022) were found to be independent risk factors for inadequate initial AB. No statistically significant difference in crude hospital mortality and 28-day mortality was observed between the treatment groups in both VAP and HAP. However we showed a significant increase in length of hospital stay, duration of mechanical ventilation and a prolonged clinical resolution in the inadequate AB group in both VAP and HAP. CONCLUSION: Our data suggests that the risk factors for inadequate initial AB are indirectly associated with the acquisition of resistant bacteria for both VAP and HAP. Although we could not find a positive correlation between adequate initial AB and survival; empirical AB with a broad spectrum should be initiated promptly to improve secondary outcomes.

Factors associated with catheter-associated urinary tract infections and the effects of other concomitant nosocomial infections in intensive care units.

BACKGROUND: Catheter-associated urinary tract infections (CAUTIs) are the most common nosocomial infections in intensive care units (ICUs). The objectives of this study were to describe the incidence, aetiology, and risk factors of CAUTIs in ICUs and to determine whether concomitant nosocomial infections alter risk factors. METHODS: Between April and October 2008, all adult catheterized patients admitted to the ICUs of Zonguldak Karaelmas University Hospital were screened daily, and clinical and microbiological data were collected for each patient. RESULTS: Two hundred and four patients were included and 85 developed a nosocomial infection. Among these patients, 22 developed a CAUTI alone, 38 developed a CAUTI with an additional nosocomial infection, either concomitantly or prior to the onset of the CAUTI, and 25 developed nosocomial infections at other sites. The CAUTI rate was 19.02 per 1000 catheter-days. A Cox proportional hazard model showed that in the presence of other site nosocomial infections, immune suppression (hazard ratio (HR) 3.73, 95% CI 1.47-9.46; p = 0.006), previous antibiotic usage (HR 2.06, 95% CI 1.11-3.83; p = 0.023), and the presence of a nosocomial infection at another site (HR 1.82, 95% CI 1.04-3.20; p = 0.037) were the factors associated with the acquisition of CAUTIs with or without a nosocomial infection at another site. When we excluded the other site nosocomial infections to determine if the risk factors differed depending on the presence of other nosocomial infections, female gender (HR 2.67, 95% CI 1.03-6.91; p = 0.043) and duration of urinary catheterization (HR 1.07 (per day), 95% CI 1.01-1.13; p = 0.019) were found to be the risk factors for the acquisition of CAUTIs alone. CONCLUSIONS: Our results showed that the presence of nosocomial infections at another site was an independent risk factor for the acquisition of a CAUTI and that their presence alters risk factors.

[Causative agents of intravenous catheter-related infections and their antibiotic susceptibilities]. / Damar Içi Kateter ile Iliskili Enfeksiyon Etkenleri ve Antibiyotik Duyarliliklari

Intravenous catheterization can lead to colonization as well as a broad spectrum of infections ranging from catheter site infections to catheter-related blood stream infections (CRBSIs). The aim of this study was to evaluate the distribution of causative agents and their antibiotic susceptibility patterns in CRBSIs and catheter site infections along with the colonization rates and colonizing microorganisms in Zonguldak Karaelmas University Hospital, Turkey. The results of cultures from catheter tips and/or intracatheter blood cultures and simultaneously taken peripheral blood cultures were sent to medical microbiology laboratory and were retrospectively investigated for 201 patients hospitalized between September 2007 and September 2009. The catheter tips were cultured by semi-quantitative and quantitative culture methods. Blood cultures from the catheters and peripheral veins were performed in BACTEC 9120 (Becton Dickinson, USA) blood culture systems. The antibiotic susceptibility tests were done by Kirby-Bauer disk diffusion method according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI). Out of 201 patients included, 28 (13.9%) had CRBSIs and 13 (6.4%) had catheter site infections while colonization was defined for 55 (27.3%) patients. Of 28 patients with CRBSIs, Acinetobacter spp. were isolated from 11 including five carbapenem-resistant strains, methicillin-resistant coagulase-negative staphylococci (MRCNS) from eight, methicillin-susceptible coagulase-negative staphylococci (MSCNS) from two, Klebsiella pneumoniae from two patients and one of each patient's cultures yielded methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Pseudomonas aeruginosa, Enterococcus spp., Escherichia coli and MRCNS + Enterococcus faecium. Of 13 patients with catheter site infections, five MSCNS, two methicillin-susceptible S.aureus (MSSA), two E.coli, and one of each K.pneumoniae, MRCNS, Enterococcus spp., K.pneumoniae + P.aeruginosa were isolated. No resistance to vancomycin and teicoplanin were detected among the staphylococci isolated from CRBSIs and catheter site infections. The distribution of the 55 colonizing microorganisms were as follows; 18 MSCNS, 18 MRCNS, four Acinetobacter spp., five K.pneumoniae, three E.coli, two MSSA, and one of each MRSA, P.mirabilis, P.aeruginosa, Corynebacterium spp., Candida albicans. In this study, the predominant microorganism isolated from CRBSIs was Acinetobacter spp., followed by coagulase-negative staphylococci. This unexpected distribution of the agents was related to the Acinetobacter spp. that have gained endemic potential following an Acinetobacter outbreak in our hospital in 2006. We emphasize that it is critical for any individual hospital to assess periodically the distribution and susceptibility profiles of isolates obtained from catheter-related infections to set out rational empirical treatment strategies.

Piperacillin-tazobactam versus carbapenem therapy with and without amikacin as empirical treatment of febrile neutropenia in cancer patients: results of an open randomized trial at a university hospital.

OBJECTIVE: Empirical beta-lactam monotherapy has become the standard therapy in febrile neutropenia. The aim of this study was to compare the efficacy and safety of piperacillin-tazobactam versus carbapenem therapy with or without amikacin in adult patients with febrile neutropenia. METHODS: In this prospective, open, single-center study, 127 episodes were randomized to receive either piperacillin-tazobactam (4 x 4.5 g IV/day) or carbapenem [meropenem (3 x 1 g IV/day) or imipenem (4 x 500 mg IV/day)] with or without amikacin (1 g IV/day). Doses were adjusted according to renal function. Clinical response was determined during and at completion of therapy. RESULTS: One hundred and twenty episodes were assessable for efficacy (59 piperacillin-tazobactam, 61 carbapenem). Mean duration of treatment was 14.8 +/- 9.6 days in the piperacillin-tazobactam group and 14.7 +/- 8.8 days in the carbapenem group (P > 0.05). Mean days of fever resolution were 5.97 and 4.48 days for piperacillin-tazobactam and carbapenem groups, respectively (P > 0.05). Similar rates of success without modification were found in the piperacillin-tazobactam (87.9%) and in the carbapenem groups (75.4%; P > 0.05). Fungal infection occurrence rates were 30.5 and 18% in piperacillin-tazobactam and carbapenem groups, respectively (P = 0.05). Antibiotic modification rates were 30.5 and 13.1% (P = 0.02) and the addition of glycopeptides to empirical antibiotic regimens rates were 15.3 and 44.3% for piperacillin-tazobactam and carbapenem groups, respectively (P = 0.001). The rude mortality rates were 14% (6/43) and 29.3% (12/41) in piperacillin-tazobactam and carbapenem groups, respectively (P = 0.08). CONCLUSIONS: The effect of empirical regimen of piperacillin-tazobactam regimen is equivalent to carbapenem in adult febrile neutropenic patients.

[An adult case of visceral leishmaniasis in a province of Black-Sea region, Turkey]. / Zonguldak'ta eriskin viseral leysmaniyaz olgusu.

Visceral leishmaniasis (VL) which is a chronic disease caused by the protozoon, Leishmania, occurs widely worldwide and it is widespread in most of the countries in the Mediterranean basin. The infection which is transmitted by a sandfly (Phlebotomus) vector, has a prolonged incubation period and insidious onset. VL generally affects children and may be fatal if not treated. In this report, a 31 years old male patient, who was the first adult VL case from Zonguldak (a province located at western Black-Sea region of Turkey) was presented. He was admitted to the hospital with two-months history of fever, chills, sweating and weight loss. There was no history of travel outside the city nor insect bites, however, he indicated that there would be unnoticed sandfly bites since sandflies were very common in the coal mines he worked. His physical examination revealed body temperatue of 39.2°C and hepatosplenomegaly, while laboratory findings yielded anemia, leucopenia, hypoalbuminemia and hypergamaglobulinemia. Erythrocyte sedimentation rate was 62 mm/h, C-reactive protein was 113 mg/L and liver transaminases were 2 to 5 folds higher than the reference values. The only pathological finding was hepatosplenomegaly in the abdominal ultrasound and computerized tomography. He was further examined to rule out infections with similar signs and symptoms, connective tissue diseases and malignancies and all were found negative. Hypercellular bone marrow were detected in the aspiration material. Bone marrow smears, bone marrow samples inoculated in NNN medium and serum samples of the patient were sent to the reference parasitology laboratory of Refik Saydam National Public Health Agency for evaluation in terms of VL. The diagnosis was confirmed by the detection of Leishmania IgG titer as 1/512 with in-house indirect immunofluorescence antibody test, by positivite rK39 Dipstick (InBios, USA) test and by the observation of Leishmania amastigote forms in the bone marrow smears. Bone marrow culture in NNN medium also revealed positive result by the determination of Leishmania promastigote forms on the 7th day. The treatment was initiated by pentavalent antimony [glucantime 1 x 10 mg/kg/day intramuscular (IM)] however, due to severe adverse effects it has switched to liposomal amphotericin B (3 mg/kg/day). The patient completely recovered without complication. In conclusion VL should be considered in the differential diagnosis of patients, even adults, with persistent fever, hepatosplenomegaly and pancytopenia, in endemic countries such as Turkey.

Specific risk factors for SARS-CoV-2 transmission among health care workers in a university hospital.

AIM: To investigate the specific risk factors for novel coronavirus (SARS-CoV-2) transmission among health care workers (HCWs) in a tertiary care university hospital. METHODS: Upper respiratory samples of HCWs were tested for SARS-CoV-2 by reverse transcriptase polymerase chain reaction. A case-control study was conducted to explore the possible risk factors that lead to SARS-CoV-2 transmission to HCWs. RESULTS: Of 703 HCWs screened between March 20 and May 20, 2020, 50 (7.1%) were found to be positive for SARS-CoV-2. The positivity rates for SARS-CoV-2 among physicians, nurses, cleaning personnel, and the other occupations were 6.3%, 8.0%, 9.1%, and 2.6%, respectively. The infection rate was 8.3% among HCWs who worked in COVID-19 units and 3.4% among those who did not work in coronavirus disease 2019 (COVID-19) units (RR = 2.449, confidence interval = 1.062-5.649, P= .027). The presence of a SARS-CoV-2 positive person in the household (P = .016), inappropriate use of personnel protective equipment while caring for patients with COVID-19 infection (P = .003), staying in the same personnel break room as an HCW without a medical mask for more than 15 minutes (P = .000), consuming food within 1 m of an HCW (P = .003), and failure to keep a safe social distance from an HCW (P = .003) were statistically significant risk factors for infection. CONCLUSION: HCWs have a high risk for SARS-CoV-2 transmission while providing care to COVID-19 patients. Transmission may also occur in nonmedical areas of the hospital while speaking or eating. Periodic screening of HCWs for SARS-CoV-2 may enable early detection and isolation of infected HCWs.

[Factors effecting the duration of hospitalization and mortality in patients with community-acquired pneumonia]. / Toplum kökenli pnömoni olgularinda hastanede yatis süresi ve mortaliteyi etkileyen faktörler.

Community-acquired pneumonia (CAP) is a common infectious disease with high morbidity and mortality. In this study, demographic features, underlying conditions, causative pathogens and factors affecting length of hospital stay and mortality were retrospectively investigated in patients who were diagnosed as CAP and followed-up in our unit between January 2005-December 2007. Among 97 patients 65 (67%) were male, 32 (33%) were female and the mean age was 62.7 (age range: 18-94) years. Patients were grouped according to criteria of Turkish Thoracic Society into four groups; 22 were group 2 (patients with risk factors, without aggrevating factors), 59 were group 3 (patients with aggrevating factors), and 16 were group 4 (patients who have necessity for intensive care) CAP. The patients have also been grouped according to criteria of American Thoracic Society (CURB-65 score = Confusion, Urea > 7 mmol/L, Respiratory rate > or = 30/min, low Blood pressure and being > or = 65 years old), as group I (n = 65), group II (n = 20), and group III (n = 12). During follow-up 11 (11.3%) patients required mechanical ventilation support and 6 (6.2%) patients have died. Causative pathogens were isolated from 14 (23.3%) out of 27 well-qualified sputum samples obtained from 60 patients who could produce sputum (8 Streptococcus pneumoniae, 2 methicillin-sensitive Staphylococcus aureus, 2 Klebsiella pneumoniae, 1 Haemophilus influenzae, 1 Moraxella catarrhalis). Thirty-seven of cases were treated with levofloxacin, 10 with moxifloxacin, 24 with ceftriaxone +/- clarithromycin, 16 with sulbactam-ampicillin +/- ciprofloxacin, 10 with beta-lactam/beta-lactamase inhibitor combinations, and fever declined within 2.5 days in 83 (85.6%) of them. The mean duration of hospital stay was estimated as 11.1 days. In the evaluation of the factors that affect the length of hospital stay, being > or = 65 years old, gender, underlying conditions, central venous catheterisation, presence of nasogastric tube, positive culture result, previous antibiotic treatment, fever continuing for > 3 days despite antibiotic therapy and scoring groups were not determined as risk factors (p > 0.05 for all of these parameters). However, mechanical ventilation was found as a significant risk factor (p < 0.05). In the evaluation of the factors that affect mortality, mechanical ventilation (p < 0.001), staying in intensive care unit (p < 0.001), being group 4 CAP (p < 0.001) and fever continuing for > 3 days despite antibiotic therapy (p = 0.05) were found to be significant risk factors. In conclusion, length of hospital stay, mortality and treatment costs in CAP patients could be reduced by defining the risk factors and starting empirical antibiotic therapy according to the national and international guidelines.

[Necrotising endocarditis of mitral valve due to Staphylococcus lugdunensis]. / Staphylococcus lugdunensis'e bagli nekrotizan mitral kapak endokarditi.

Staphylococcus lugdunensis is an infrequent cause of infective endocarditis (IE) and usually involves native valves of the heart. It causes life-threatening events such as rupture of cardiac valve or cerebral or pulmonary embolism due to necrosis on the endocardial tissue involved by the bacteria. Antibiotic therapy without cardiac surgery or delayed cardiac surgery usually follows a fatal course in S. lugdunensis endocarditis. In this report the first case of S. lugdunensis endocarditis from Turkey was presented. A 37-year-old man was admitted to the emergency department with a 2-weeks history of fever chills and accompanying intermittent pain on the left side of the thorax. Other than recurrent folliculitis continuing for 20 years, his history was unremarkable. Echocardiography revealed vegetation on the mitral valve of the patient and vancomycin plus gentamicin were initiated with the diagnosis of IE. All blood cultures (5 sets) taken on admission and within the initial 48 hours of the antibiotic therapy yielded S. lugdunensis. According to the susceptibility test results, the antibiotic therapy was switched to ampicillin-sulbactam plus rifampin. Blood cultures became negative after the third day of therapy, however, cardiac failure was emerged due to rupture of mitral valve and chorda tendiniea on the 12th day of the therapy. Cardiac surgery revealed that mitral valve and surrounding tissue of the valve were evidently necrotic and fragile, anterior leaflet of the mitral valve was covered with vegetation, posterior leaflet and chorda tendiniea were ruptured. Vegetation was removed and the destructed mitral valve was replaced with a mechanical valve. Vegetation culture remained sterile, however, antibiotics were switched to vancomycin plus rifampin due to persistent fever on the 21st day of the therapy (9th day of operation). Fever resolved four days after the antibiotic switch. Antibiotics were stopped on the 9th weeks of admission and the patient was discharged. He had no problem in follow-up controls for one year. In conclusion, proper antibiotic therapy combined with early cardiac surgery seems to be the optimal therapeutic approach in IE caused by S. lugdunensis.

Risk factors and clinical responses of pneumonia patients with colistin-resistant Acinetobacter baumannii-calcoaceticus.

BACKGROUND: Nosocomial infections with carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (ABC) strains are great problem for intensive care units. ABC strains can develop resistance to all the antibiotics available. Carbapenem resistance is common and colistin resistance is rare in our country. Knowing the risk factors for colistin resistance is important since colistin seems to be the only remaining therapeutic option for the patients with pneumonia due to extensively drug resistant ABC for our country. AIM: To investigate the comparison of clinical responses and outcomes between pneumonia patients with colistin-susceptible and -resistant Acinetobacter sp. Strains. METHODS: During the study period, 108 patients with pneumonia due to colistin-susceptible strains and 16 patients with colistin-resistant strains were included retrospectively. Continuous variables were compared with the Mann-Whitney U test, and categorical variables were compared using Pearson's chi-square test or Fisher's Exact chi-square test for two groups. A binary logistic regression model was developed to identify the potential independent factors associated with colistin resistance in patients with colistin-resistant strains. RESULTS: High Acute Physiology and Chronic Health Evaluation II scores (OR = 1.9, 95%CI: 1.4-2.7; P < 0.001) and prior receipt of teicoplanin (OR = 8.1, 95%CI: 1.0-63.3; P = 0.045) were found to be independent risk factors for infection with colistin-resistant Acinetobacter sp. Different combinations of antibiotics including colistin, meropenem, ampicillin/sulbactam, amikacin and trimethoprim/sulfamethoxazole were used for the treatment of patients with colistin-resistant strains. Although the median duration of microbiological cure (P < 0.001) was longer in the colistin-resistant group, clinical (P = 0.703), laboratory (P = 0.277), radiological (P = 0.551), microbiological response (P = 1.000) and infection related mortality rates (P = 0.603) did not differ between the two groups. Among the patients with infections due to colistin-resistant strains, seven were treated with antibiotic combinations that included sulbactam. Clinical (6/7) and microbiological (5/7) response rates were quite high in these patients. CONCLUSION: The optimal therapy regimen is unclear for colistin-resistant Acinetobacter sp. infections. Although combinations with sulbactam seems to be more effective in our study patients, data supporting the usefulness of combinations with sulbactam is very limited.

Dynamics of Puumala hantavirus outbreak in Black Sea Region, Turkey.

BACKGROUND: Some of the hantavirus species in Euro-Asia cause haemorrhagic fever with renal syndrome (HFRS) in humans. The first documented human hantavirus infection in Turkey was diagnosed in 2009. This report describes the dynamics of the first hantavirus outbreak that emerged in humans in the Western Black Sea Region of Turkey. METHODS: All the suspected cases of hantavirus infection were admitted to the Infectious Diseases and Clinical Microbiology Department at the Zonguldak Bülent Ecevit University Hospital in Zonguldak, Turkey. The patients were carefully interviewed, examined and evaluated using routine laboratory tests and hantavirus diagnostic tools. Hantavirus-reactive antibodies (IgM and IgG) in serum samples were detected via enzyme immune assay (EIA) and immunofluorescence assay (IFA) in the acute and convalescence stages of the disease. The presence of hantavirus ribonucleic acid (RNA) was analysed via reverse transcription polymerase chain reaction (RT-PCR) in serum and urine samples. A focus reduction neutralization test (FRNT) was performed to confirm specific hantavirus serotypes. In addition, a case-control study was conducted to identify possible risk factors for hantavirus transmission in the outbreak area. A control group was composed of asymptomatic individuals who were seronegative for hantavirus IgM and IgG and living in the outbreak area. RESULTS: A total of 55 suspected cases of hantavirus infection were admitted to the inpatient clinic between February and June of 2009. Twenty-four patients were diagnosed with acute HFRS via EIA or IFA. In 22 of the 24 infected patients, Puumala virus (PUUV) was identified as the causative hantavirus type by detecting IgM in the acute stage and an increase in the IgG level in follow-up serum samples. PUUV was also verified as the infecting agent by FRNT in two of the 24 cases. Among the 24 laboratory-confirmed HFRS cases, 21 (87.5%) were males and 3 (12.5%) were females, and the mean age was 45.92 years (standard deviation ± 16.90 years). Almost all these individuals were living in villages or rural areas. The 24 HFRS cases were matched with 26 healthy controls for statistical analyses and according to binary logistic regression analysis, and dealing with rodent control activities in gardens or in annexes of their homes (p = 0.021 and Odds ratio [OR] = 17.11) and being male (p = 0.019 and OR = 22.37) were detected as statistically significant risk factors for hantavirus infection. The most commonly observed clinical complaints were fatigue (95.8%), shivering (91.7%), fever (87.1%), headache (70.8%) and nausea (70.8%). Haemodialysis was required for four patients (16.7%). Except for the first case diagnosed with acute hantavirus infection, no patient died. The mean delay time to hospital admission from initiation of symptoms was 5.3 days, the mean duration of febrile days was 2.6 days, and the mean duration of hospital stay was 8.5 days. CONCLUSION: Hantaviruses are circulating in Turkey and causing sporadic or epidemic infection in humans. Additional investigations are needed to better understand the dynamics of hantaviruses in this country.

[Infective endocarditis due to high level aminoglycoside resistant Enterococcus faecalis and methicillin resistant coagulase-negative staphylococci presenting with rheumatic manifestations]. / Romatolojik bulgularla seyreden, yüksek düzey aminoglikozid direnci gösteren Enterococcus faecalis ve metisiline dirençli koagülaz-negatif stafilokokun etken oldugu enfektif endokardit olgusu.

Infective endocarditis has variable clinical presentations and may present with rheumatologic manifestations. Infective endocarditis due to high level aminoglycoside resistant enterococci represents a severe therapeutic challenge as none of the currently recommended treatment regimens are bactericidal against these isolates. In this report, a case of infective endocarditis with double aetiology, high level aminoglycoside resistant Enterococcus faecalis together with methicillin-resistant coagulase-negative staphylococci (MR-CNS), presenting with leukocytoclastic vasculitis and rapidly progressive glomerulonephritis, has been presented. A 48-years-old woman was admitted to our hospital with malaise and non-pruritic purpural rush on her lower extremities. On admission she had no fever or leukocytosis. Skin biopsy showed leukocytoclastic vasculitis and steroid therapy was started. On 12th day of admission rapidly progressive glomerulonephritis was diagnosed and she received plasmapheresis and haemodialysis support. Transthoracic echocardiography (TTE) demonstrated 1 x 1.5 cm vegetation on the mitral valve. An initial diagnosis of infective endocarditis was made and empirical treatment with vancomycin and gentamicin was started. All blood cultures yielded high level aminoglycoside resistant E. faecalis and additionally two of them yielded MR-CNS. Vancomycin was administered in combination with high dose ampicillin and repeated blood cultures taken after administration of ampicillin, revealed no growth. The patient remained afebrile, renal functions improved and a repeat TTE done on 20th day of ampicillin therapy showed waning of the vegetation. On 42nd day of treatment repeat TTE showed new vegetation on the mitral valve and severe valve insufficiency, so the patient was scheduled for mitral valve replacement. She was treated for 12 weeks with vancomycin and ampicillin and recovered successfully. In conclusion; infective endocarditis should be considered in the differential diagnosis of leukocytoclastic vasculitis and rapidly progressive glomerulonephritis. Physicians should document their treatment outcomes and experience with high level aminoglycoside resistant enterococcal infective endocarditis, which is a therapeutic challenge, so that the best therapeutic options can be identified.

[Cryptococcus neoformans meningitis in a HIV negative miliary tuberculosis-suspected patient]. / Hiv negatif miliyer tüberküloz süpheli bir hastada Cryptococcus neoformans menenjiti.

Cryptococcosis caused by Cryptococcus neoformans has a wide range of clinical presentations, varying from asymptomatic colonization of the respiratory airways to the dissemination of infection into different parts of body. It is more common among immunosupressed patients such as human immunodeficiency virus (HIV) positive ones. In this report we present a case with C. neoformans meningitis and miliary pulmonary infiltrates suggesting pulmonary tuberculosis without HIV infection. A-70-years-old male was admitted to the hospital with mental confusion, 3-weeks history of headache, weight loss, dry cough and fatigue. Physical examination was normal except neck stiffness. Cerebrospinal fluid (CSF) white cell count was 120/mm3 (80% polimorphonuclear cells). Gram staining of CSF revealed poorly stained gram-positive yeast cells. Empirical therapy with lipozomal amphotericin B, ceftriaxone and ampicillin combination was started. When C. neoformans growth was detected on CSF culture, ceftriaxone and ampicillin were discontinued. Patient became conscious at 24th hour of the treatment. Peripheric blood flow-cytometric analysis revealed a significant decrease in absolute CD4+ T lymphocytes, and in CD8+28+ T lymphocytes in addition a significant increase in natural killer cell ratio. Blood immunoglobulin and complement levels were found normal. Cranial magnetic resonance imaging and computerized tomogralphy (CT) of the abdomen were normal, however, chest CT revealed multiple parenchymal millimetric nodular infiltrations on both sides and minimal fibrotic alterations. Acid-fast staining of CSF, tuberculosis culture, tuberculosis PCR results and repeated HIV serology were found negative. Despite the lack of microbiological confirmation, empirical antituberculosis treatment was also started with the suspicion of miliary tuberculosis as the patient had a symptom of long-term dry cough, miliary infiltrations on chest CT, anergic tuberculin skin test and a history of pulmonary tuberculosis in childhood. After two weeks, amphotericin B was changed to oral fluconazole which was continued for an additional eight weeks. Antituberculosis therapy was given for nine months. Control chest CT taken after four months of antituberculosis therapy revealed improvement of the lesions. This presentation emphasizes the fact that cryptococcal infections may develop in HIV negative patients, even together with tuberculosis in certain cases and radiological findings of the two infections may be confusing when both of them invade the lungs.

[Mediterranean spotted fever due to contact with dog-tick]. / Köpek kenesi ile temas sonrasinda gelisen akdeniz benekli atesi.

Mediterranean spotted fever (MSF) is one of the tick-borne rickettsial infections caused by Rickettsia conorii. It is transmitted to humans by brown dog ticks (Rhipicephalus sanguineus). In this case report, a 16-years-old male patient who was diagnosed as MSF after an exposure to dog-tick in Bartin province (located at middle Black Sea region of Turkey) has been presented. His history revealed that, five days before admission to the hospital (on June, 2007) he had cleaned dog-ticks from his dog, and after 12 hours he found a stucked tick on his leg and he took it out right away with a tweezer. High fever, headache and generalized maculopapular rash including soles and palms and a black-colored lesion at the tick bite site developed three days later. In clinical examination, there was a black escar circled with a red-purple colored halo in front of the right tibia at the site of the tick bite showing high similarity to "tache noire" which was specific to MSF. Indirect immunofluorescence assay (IFA) for Rickettsia yielded negative result in the serum sample collected on admission day, however, it was found positive at 1/512 titer in the serum sample collected 10 days after admission. The patient has recovered completely without any complication after 10 days of doxycycline therapy. The aim of this presentation is to point out that MSF should be considered for the differential diagnosis of a patient with a history of tick bite, fever, maculopapular rash, headache, myalgia, arthralgia and especially with black escar during summer months in our country where the incidence of tick-borne infections has been increasing since recent years.

Development and validation of a modified quick SOFA scale for risk assessment in sepsis syndrome.

Sepsis is a severe clinical syndrome owing to its high mortality. Quick Sequential Organ Failure Assessment (qSOFA) score has been proposed for the prediction of fatal outcomes in sepsis syndrome in emergency departments. Due to the low predictive performance of the qSOFA score, we propose a modification to the score by adding age. We conducted a multicenter, retrospective cohort study among regional referral centers from various regions of the country. Participants recruited data of patients admitted to emergency departments and obtained a diagnosis of sepsis syndrome. Crude in-hospital mortality was the primary endpoint. A generalized mixed-effects model with random intercepts produced estimates for adverse outcomes. Model-based recursive partitioning demonstrated the effects and thresholds of significant covariates. Scores were internally validated. The H measure compared performances of scores. A total of 580 patients from 22 centers were included for further analysis. Stages of sepsis, age, time to antibiotics, and administration of carbapenem for empirical treatment were entered the final model. Among these, severe sepsis (OR, 4.40; CIs, 2.35-8.21), septic shock (OR, 8.78; CIs, 4.37-17.66), age (OR, 1.03; CIs, 1.02-1.05) and time to antibiotics (OR, 1.05; CIs, 1.01-1.10) were significantly associated with fatal outcomes. A decision tree demonstrated the thresholds for age. We modified the quick Sequential Organ Failure Assessment (mod-qSOFA) score by adding age (> 50 years old = one point) and compared this to the conventional score. H-measures for qSOFA and mod-qSOFA were found to be 0.11 and 0.14, respectively, whereas AUCs of both scores were 0.64. We propose the use of the modified qSOFA score for early risk assessment among sepsis patients for improved triage and management of this fatal syndrome.

[Evaluation of 35 adult measles cases detected in a measles outbreak]. / Kizamik salgininda saptanan 35 eriskin kizamik olgusunun degerlendirilmesi.

The aim of this study was to evaluate the clinical, epidemiological and demographical features of adult measles cases admitted to our hospital, during the measles epidemic which emerged in Europe and in our country in the year 2001. A total of 35 adult measles cases (10 male, 25 female) ages between 16-36 (mean age: 23.1 +/- 4.6) years were detected between January and June 2001. The diagnosis was based on the clinical findings, however only 11 of the cases could be serologically confirmed with the presence of measles IgM antibody positivities. Fever (91.4%), cough (94.3%) and conjunctivitis (77.1%) were the most common symptoms. All of the patients had maculopapular rash, and the presence of Koplik spots, lymphadenopathy and hepatomegaly were observed in 77.1%, 57.1%, and 5.7% of patients, respectively. Leukopenia and elevated liver enzymes were detected in 28.5% and 37.2% of the patients, respectively. Pneumonia was the most common complication which was seen in 20% of the patients. Of the cases 2.9% exhibited otitis media and 17.1% diarrhea. Spontaneous abortus occurred in one of the three pregnant women. In conclusion, measles is still an important public health problem in our country, and since it may lead to severe complications and economic and labor loss, an effective elimination programme should be obtained by the use of vaccine in two doses and effective strategies for the immunization of the target populations.

[A severe case of Weil's disease]. / Agir seyirli bir weil hastaligi olgusu.

Leptospirosis which is caused by Leptospira species, may present with clinical features that vary from a mild flu-like illness to an acute life-threatening condition. Weil's disease, the most severe form of leptospirosis is characterized by multiorgan involvement including liver, kidney and lungs. In this report a severe Weil's disease was presented. A 43 years old male patient who had a history of swallowing water while swimming in the creek, was admitted to the hospital with the complaints of weakness, cough, bloody sputum, generalized jaundice and dark urine. Acute renal failure, bilateral lung infiltration, hyperbilirubinemia, leukocytosis and thrombocytopenia were detected, and the patient has undergone to hemodialysis. Ceftriaxone and ciprofloxacin treatment was applied to the patient after collection of blood, urine and sputum cultures and serum samples for serological tests. None of the cultures yielded pathogenic microorganisms. Microscopic agglutination test (MAT) was applied to two serum samples which were collected with 10 days interval. The first serum sample revealed antibody positivity at 1/200 titer against L. semeranga Patoc I, while the second serum revealed antibody positivity at 1/400 titer against both L. semeranga Patoc I and L. icterohaemorrhagiae Wijnberg. By the administration of antibiotic therapy and early supportive care the patient was cured completely. In conclusion Weil's disease should be taken into consideration in the patients with multiple organ involvements.