Analysis of epidemiology and risk factors for mortality in ventilator-associated pneumonia attacks in intensive care unit patients.

BACKGROUND/AIM: The aim of this study was to investigate the epidemiologic characteristics, the causative microorganisms and their antimicrobial susceptibility patterns, and the prognostic risk factors for mortality in critically ill patients with ventilator-associated pneumonia (VAP). MATERIALS AND METHODS: In this retrospective observational study, all the critically ill patients with VAP hospitalized in a medical/surgical intensive care unit (ICU) between January 2010 and June 2015 were evaluated. Patients' demographic features and microbiological data were reviewed. RESULTS: A total of 417 patients were clinically diagnosed with VAP; 51.1% of them were male and the average age was found as 69.9 ± 15.9 years. VAP was detected at approximately 25.0 ± 18.0 days of ICU stay and 17.9 ± 12.6 days after intubation. Acinetobacter baumannii (69.5%) was isolated as the most frequent VAP agent, and the most effective antibiotic was colistin. The crude mortality rate was detected as 39.8% among the patients. The presence of dyspnea at admission, coronary heart disease as a comorbidity, unconsciousness at admission, steroid usage, and prolonged hospital stay were observed as independent risk factors in multivariate analysis (P < 0.01). CONCLUSION: According to the etiological microorganisms and antimicrobial susceptibility patterns, colistin was found to be the most reliable antibiotic for empirical antimicrobial therapy.

A case of Crimean-Congo hemorrhagic fever complicated with acute pancreatitis.

BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease characterized by nonspecific symptoms like fever, myalgia, severe headache, nausea, vomiting, diarrhea, and abdominal pain. It can result in various complications during the course of the disease due to the diffuse endothelial injury involved in the pathogenesis of CCHF. OBJECTIVES: Here we present a patient with CCHF complicated by acute pancreatitis, including pleural and intra-abdominal effusions. CASE REPORT: A 70-year-old patient was referred to our hospital from an endemic area with the suspicion of CCHF. The physical examination of the patient revealed high fever (38°C), somnolence, and petechial eruption. The diagnosis of case was confirmed with positive reverse transcriptase polymerase chain reaction (RT-PCR). The viral load of the patient was 4×10(9) copies/mL. On the fifth day of admission, upper abdominal pain, scleral ichter, and abdominal distention developed. The patient had abdominal tenderness with guarding. The laboratory tests revealed an amylase level of 1740 U/L (28-100), lipase level of 583 U/L (13-60), and total bilirubin level of 3.75 mg/dL (<0.3). The diagnosis of acute pancreatitis was confirmed with radiological findings. CONCLUSIONS: Until now, atypical presentations of CCHF have been reported in some case reports, but not acute pancreatitis. To the best of our knowledge, this is the first case of acute pancreatitis in the literature seen in the course of CCHF.

Two cases of acute hepatitis after a serial knife stabbing.

Three persons became victims of a serial knife stabbing in a fight. Three months later, one of the victims presented with acute hepatitis. On the fifth day of his admission to the hospital, another victim of this serial stabbing presented to our clinic with acute hepatitis B infection. The patients told that the first victim stabbed in this fight was their relative and he was a carrier of hepatitis B virus for a long time. They said that the carier of hepatitis B was stabbed first and then, with the same knife, the first and second patients were stabbed, respectively. After 8 months, the index case (first victim) was admitted to our clinic with elevation of liver enzymes. HBsAg and HBeAg were positive. HBV DNA was 2 × 10 (9) copy/mL. Histopathologic examination of liver biopsy showed chronic hepatitis with histologic activity index of 6/18 and grade I fibrosis.

Can hantavirus infections be predicted on admission to hospital?

The aim of this study was to investigate the predictive factors which contribute to diagnosis of hantavirus infection. One hundred patients from rural areas hospitalized with a preliminary diagnosis of hantavirus infection from different hospitals in Turkey were investigated. Hantavirus infection was confirmed in 20 patients (Group 1) using immunofluorescence and immunoblot assays at the Refik Saydam National Public Health Agency. Hantaviruses were not detected in the serum of the remaining 80 patients, other infectious and non-infectious diseases being diagnosed in this group (Group 2). Patients' demographic characteristics and clinical and laboratory data on admission were examined and compared between the two groups. Fever, proteinuria, hematuria, lethargy-weakness, and nausea-vomiting were the most frequent symptoms and findings in Group 1, seen in almost all patients. Proteinuria, hematuria, muscle pain, diarrhea/abdominal pain, hypotension, shock, and sweating were observed at significantly higher levels in Group 1 compared to Group 2. Serum urea, creatinine, uric acid, lactate dehydrogenase (LDH), aspartate transaminase (AST), alkaline phosphatase (ALP), and C-reactive protein (CRP) were significantly higher, but serum platelet counts were lower in Group 1 patients. Area beneath the receiver operating characteristics (ROC) curve analysis was used to calculate the discriminative ability of various laboratory values to identify patients with hantavirus infection. This analysis revealed that, serum CRP had a 100% negative predictive value, whilst, platelet, and creatinine had 75% and 70% positive predictive values for the diagnosis of hantavirus infection. In summary, laboratory markers used in clinical practice are of great importance predicting hantavirus infections.

Subclinical infections with Crimean-Congo hemorrhagic fever virus, Turkey.

To investigate Crimean-Congo hemorrhagic fever virus in Turkey, we conducted a seroepidemiologic survey during January-April 2009. Seroprevalence of infection was 10% in a sample from an outbreak region and increased with patient age, indicating that the virus had been previously present in Turkey. We also estimated that 88% of infections were subclinical.

[Evaluation of tularemia cases originated from Central Anatolia, Turkey]. / Orta Anadolu Kaynakli Tularemi Olgularinin Degerlendirilmesi.

Tularemia is an infection caused by Francisella tularensis with a worldwide distribution and diverse clinical manifestations. In recent years, tularemia cases are increasing in Turkey, with a special attention to Marmara, western Blacksea and Central Anatolia regions. The aim of this study was to evaluate tularemia cases admitted to our hospital during an outbreak emerged at Central Anatolia between December 2009 and September 2010, making a point for the disease. A total of 32 patients (17 female, 15 male; age range: 15-80 years, mean age: 41 ± 16 years) with fever, sore throat, cervical mass and failure to respond to beta-lactam antibiotics, were followed up with the preliminary diagnosis of tularemia. The diagnosis was confirmed by specific laboratory tests. Serum samples were obtained from 25 patients and in 17 (68%) of them microagglutination test yielded positive result (≥ 1/160) in their first serum samples. All of the 8 patients who had negative results in their first samples (< 1/160), revealed seroconversion in their second samples. In 10 (91%) of the 11 patients from whom lymph node aspirates were obtained, PCR performed with species specific (tul4) primers yielded positivity and subspecies differentiation done by RD1 primers identified the agent as F.tularensis subspecies holarctica. F.tularensis growth was not detected in the cultures of lymph aspirates and/or throat swabs of the cases (n= 16). All the patients had oropharyngeal tularemia and eight of them also had oculoglandular form. The mean duration of the symptoms were 25.6 ± 17.2 (2-60) days. They had a history of oral intake of contaminated water. Cervical or submandibular lymphadenopathy were detected in all patients. One patient had cervical abscess and the other one had erythema nodosum. Elevated sedimentation rate was found in 26 (81.3%) patients and elevated CRP in 24 (75%) patients. Spontaneous drainage was detected in nine cases during follow-up. Lymph node aspiration was performed in patients when fluctuation was detected. Streptomycin 2 g/day for 10 days was given to 21 patients and doxycycline 2 x 100 mg for 14 days was given to 11 patients. Twelve (37.5%) patients received further antibiotic treatment since they failed to respond to the first therapy. Of the patients, 21 recovered completely and two patients had lymph node excision. No severe complications were observed. The patients who applied to the hospital within 10 days of the initiation of the symptoms were treated successfully, while the others that applied later were not. In conclusion, tularemia which is an endemic disease in Turkey, should be kept in mind in patients with fever, sore throat and lymphadenopathy.

Effect of oral ribavirin treatment on the viral load and disease progression in Crimean-Congo hemorrhagic fever.

OBJECTIVES: Crimean-Congo hemorrhagic fever (CCHF) is a lethal hemorrhagic disease. There is currently no specific antiviral therapy for CCHF approved for use in humans. In this study we aimed to investigate the effect of oral ribavirin treatment on the viral load and disease progression in CCHF. METHODS: The study population was composed of patients who had a definitive diagnosis of CCHF by means of clinical presentation plus detection of viral RNA by reverse transcriptase polymerase chain reaction (RT-PCR). Ten patients who received oral ribavirin for 10 days and 40 control patients who received supportive treatment only were included in the study. Ribavirin treatment consisted of oral ribavirin 4 g/day for 4 days and then 2.4 g/day for 6 days. Viral load and hematological and biochemical laboratory parameters, which were measured daily, were analyzed. RESULTS: Mean age (37.4 vs. 45.5, p=0.285), gender (male 50% vs. 62.5%, p=0.470), days from the appearance of symptoms to admission (4.3 vs.4.4 days, p=0.922), and initial complaints were similar between the ribavirin group and the control group. Upon hospital admission, mean viral load was 8.2×108 copies/ml in the ribavirin group and 8.3×108 copies/ml in the control group (p=0.994). During follow-up, no statistically significant differences were found between the groups with regard to the decrease in viral load, the reduction in alanine aminotransferase and aspartate aminotransferase levels, and the increase in platelet count. The case-fatality rate was 20% (2/10 patients) in the ribavirin group and 15% (6/40 patients) in the control group (p=0.509). CONCLUSION: In this study, oral ribavirin treatment in CCHF patients did not affect viral load or disease progression.

Evidence of vascular endothelial damage in Crimean-Congo hemorrhagic fever.

BACKGROUND: Endothelial infection has an important role in the pathogenesis of Crimean-Congo hemorrhagic fever (CCHF). In this study, we investigated the causes of vascular endothelial damage in patients with CCHF. METHODS: This prospective case-controlled study was carried out at Ankara Numune Education and Research Hospital between April and September 2007. Seventy-five patients with a laboratory-confirmed diagnosis of CCHF and 88 healthy controls were enrolled in the study. Serum levels of soluble cell adhesion molecules (sICAM-1, sVCAM-1, sE-selectin, sP-selectin, sL-selectin), vascular endothelial growth factor (VEGF), and macrophage migration inhibitory factor (MIF) were investigated in these patients by quantitative sandwich ELISA technique. RESULTS: In the patient group, serum levels of sVCAM-1, sL-selectin and MIF were significantly higher than in the control group; serum levels of sICAM-1, sP-selectin, sE-selectin, and VEGF were significantly lower than in the control group. Serum levels of sVCAM-1 and sICAM-1 were significantly higher in severe cases than in non-severe cases, whereas the serum level of VEGF was significantly lower. sVCAM-1 was significantly higher in non-survivors than in survivors, while serum VEGF was significantly lower in non-survivors. The optimum cut-offs of sVCAM-1 and VEGF for the prediction of mortality were 205 ng/ml and 125 ng/ml, respectively. At these cut-offs, sVCAM-1 and VEGF had a sensitivity of 100% and specificity of 42.5% and 54.5%, respectively, in identifying CCHF patients who would die from the disease. The positive predictive values were 19% and 23%, respectively; negative predictive values were 100% for both. CONCLUSION: Endothelial activation can affect the course of CCHF, and vascular endothelial damage is probably indirect. Further studies are needed for general conclusions to be drawn.

Detection of Crimean-Congo hemorrhagic fever virus genome in saliva and urine.

BACKGROUND: The Crimean-Congo hemorrhagic fever (CCHF) virus is transmitted by tick bites and by contact with the blood or tissues of infected patients and livestock. This study was designed to investigate the genome of CCHF virus in saliva and urine samples of patients with CCHF. METHODS: Eight patients with laboratory-confirmed CCHF were included in the study. The diagnosis was made by detection of viral RNA in blood by real-time reverse transcriptase-polymerase chain reaction (real-time RT-PCR). Samples of saliva from six patients and samples of urine from three patients were collected at the same time as the blood samples and analyzed for viral RNA. RESULTS: The genome of CCHF virus was detected in the saliva from five of the six patients and in the urine from two of the three patients. The levels of viral load in the saliva and urine samples were similar to those in the blood samples in all but one patient, in whom higher levels were detected in blood compared to saliva or urine. CONCLUSIONS: This study shows that during human infection with CCHF virus, viral genomes are present in the saliva and urine. Further studies to isolate infectious viruses from these fluids and to study whether they represent an infectious risk are underway.

Serum chitotriosidase enzyme activity in patients with Crimean-Congo hemorrhagic fever.

BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF) is a public health problem in many countries. Chitotriosidase (ChT) is an enzyme secreted by activated macrophages that catalyzes the hydrolysis of chitin and chitin-like substrates. The goal of this study was to assess the relationship between serum ChT activity and mortality. METHODS: ChT activities on the first day of hospitalization were analyzed in serum from 46 patients with CCHF and 36 healthy controls. Serum ChT activities and other clinical and laboratory parameters for patients with non-fatal and fatal CCHF were compared. RESULTS: The median ChT activity was increased in all patients with CCHF [189.9 (134.8-246.6) nmol/mL/h]. The median ChT activity in the non-fatal CCHF group [220.2 (180.6-290.1) nmol/mL/h] was higher compared with the fatal CCHF group [29.2 (16.5-45.7) nmol/mL/h] (p<0.001). In univariate analysis, platelet count, lactate dehydrogenase (LDH), and activated partial thromboplastin time were associated with mortality. CONCLUSIONS: This is the first study investigating the association of serum ChT enzyme activity with mortality from CCHF. This study suggested that relatively low ChT enzyme activities may be a prognostic marker in patients with CCHF.

Analysis of lymphocyte subgroups in Crimean-Congo hemorrhagic fever.

OBJECTIVES: This study examined the association between lymphocyte subgroups and mortality in patients with Crimean-Congo hemorrhagic fever (CCHF) in Turkey. METHODS: During the spring and summer of 2007, peripheral blood was collected from hospitalized patients with suspected CCHF. Lymphocyte subgroups were characterized by fluorescence-activated cell sorting. CCHF cases were confirmed by detecting viral RNA by PCR and/or IgM antibodies by ELISA. Lymphocyte subgroups were compared between fatal and non-fatal cases. The correlation between lymphocyte subgroups and viral loads was also investigated. RESULTS: Seventy-seven confirmed cases of CCHF were included in this study (five cases were fatal (6.5 %)). No differences in lymphocyte subgroups were found between fatal and non-fatal cases, except for significantly higher CD3+CD8+ T cells in the fatal cases (p=0.017). A positive correlation between viral load and CD3+CD8+ T cells was also detected (p=0.044). There was no correlation between other lymphocyte subgroups and viral load. CONCLUSIONS: Higher levels of CD3+CD8+ T lymphocytes were detected in fatal compared to non-fatal CCHF cases. Despite this cytotoxic immune activation, a fatal outcome could not be prevented. We hypothesize that high viral load and other factors may influence this outcome, although more studies are required to explain the pathogenesis of CCHF.

High serum levels of neopterin in patients with Crimean-Congo hemorrhagic fever and its relation with mortality.

OBJECTIVE: Neopterin is generated and released in increased amounts by macrophages upon activation by interferon-gamma during cellular immune response. In this study, we aimed to investigate serum neopterin levels in patients with Crimean-Congo hemorrhagic fever (CCHF) and its clinical significance as a predictor factor of mortality. METHODS: Neopterin concentrations on the first day of hospitalization were measured in serum samples from 51 CCHF patients. Serum neopterin levels and other clinical-laboratory parameters for fatal and nonfatal CCHF patients were compared. RESULTS: Serum neopterin levels (73.22+/-54.30 nmol/L) were highly elevated in all CCHF patients (p<0.0001) with higher levels in fatal group (153.66+/-81.34 nmol/L, p=0.0001) compared to nonfatal disease (55.99+/-24.09 nmol/L). In univariate analysis, the level of neopterin on the first day of hospitalization, bleeding, platelet count, aspartate transferase and lactate dehydrogenase were associated with mortality. In multivariate analysis, only the serum level of neopterin was associated with mortality. As a mortality risk factor, area under the curve was 0.939 (p=0.0001, 95% confidence interval: 0.85-1.00). CONCLUSIONS: In this first study of serum neopterin levels for CCHF, elevated serum neopterin level showing strong activation of monocytes/macrophages was a risk factor for CCHF.

Risk factors for nosocomial imipenem-resistant Acinetobacter baumannii infections.

OBJECTIVES: To identify the risk factors for nosocomial imipenem-resistant Acinetobacter baumannii (IRAB) infections. METHODS: A prospective case-control study, set in an 1100-bed referral and tertiary-care hospital, of all patients who had nosocomial A. baumannii infections between January 1 and December 31, 2004. Only the first isolation of A. baumannii was considered. RESULTS: IRAB was isolated from 66 (53.7%) patients and imipenem-sensitive Acinetobacter baumannii (ISAB) was isolated from 57 (46.3%) patients during the study period. The mean duration of hospital stay until A. baumannii isolation was 20.8+/-13.6 days in IRAB infections, whereas it was 15.4+/-9.4 days in ISAB infections. Of the patients, 65.2% with IRAB infections and 40.4% with ISAB infections were followed at the intensive care unit (ICU). Previous carbapenem use was present in 43.9% of the patients with IRAB and 12.3% of the patients with ISAB infection. In univariate analysis female sex, longer duration of hospital stay until infection, ICU stay, emergent surgical operation, total parenteral nutrition, having a central venous catheter, endotracheal tube, urinary catheter or nasogastric tube, previous antibiotic use, and previous administration of carbapenems were significant risk factors for IRAB infections (p<0.05). In multivariate analysis, longer duration of hospital stay until A. baumannii isolation (odds ratio (OR) 1.043; 95% confidence interval (CI) 1.003-1.084; p=0.032), previous antibiotic use (OR 5.051; 95% CI 1.004-25.396; p=0.049), and ICU stay (OR 3.100; 95% CI 1.398-6.873; p=0.005) were independently associated with imipenem resistance. CONCLUSIONS: Our results suggest that the nosocomial occurrence of IRAB is strongly related to an ICU stay and duration of hospital stay, and that IRAB occurrence may be favored by the selection pressure of previously used antibiotics.

Breastfeeding in Crimean-Congo haemorrhagic fever.

Crimean-Congo haemorrhagic fever (CCHF) is potentially a fatal disease transmitted by tick bite, close contact with blood or tissues of infected humans or viraemic livestock. We present the clinical course of 2 breastfeeding women with CCHF and their babies. Both the mothers had positive reverse transcriptase-polymerase chain reaction for CCHF virus in blood and it was negative in breast milk. At follow-up, babies did not develop CCHF infection.

Imipenem-resistant Pseudomonas aeruginosa: risk factors for nosocomial infections.

The aim of this study was to determine the risk factors for nosocomial infections of imipenem-resistant Pseudomonas aeruginosa (IRPA). A prospective case-control study was performed at a tertiary care hospital in Ankara from January to December 2004. The patients with nosocomial P. aeruginosa infection were included in the study. The features of the patients with IRPA infections were compared to those with imipenem-sensitive P. aeruginosa (ISPA) infections. Only the first isolation of P. aeruginosa was considered. Nosocomial infections were defined according to Center for Disease Control (CDC) criteria. IRPA was isolated from 75 (44.1%) patients, and ISPA was isolated from 95 (55.9%) patients during the study period. IRPA were most frequently isolated from endotracheal aspirate (19%) cultures (p=0.048), whereas ISPA were most frequently isolated from urine (28%) cultures (p=0.023). In multivariate analysis, a longer duration of hospital stay until P. aeruginosa isolation (odds ratio [OR], 1.027; 95% confidence interval [CI], 1.002-1.054, p=0.034), arterial catheter administration (OR, 2.508; 95% CI, 1.062-5.920, p=0.036), vancomycin (OR, 2.882; 95% CI, 1.130-7.349, p=0.027), piperacillin-tazobactam (OR, 6.425; 95% CI, 2.187-18.875, p=0.001), and imipenem (OR, 3.580; 95% CI, 1.252-10.245, p=0.017) treatment within the 14 days before isolation of IRPA were independently associated with imipenem resistance. It was concluded that treatment with imipenem, vancomycin and piperacillin-tazobactam were major risk factors for IRPA infections in hospitalized patients. The nosocomial occurrence of IRPA was also strongly related to the duration of hospital stay, arterial catheter administration.

Viral load as a predictor of outcome in Crimean-Congo hemorrhagic fever.

Crimean-Congo hemorrhagic fever (CCHF) is a potentially fatal disease affecting multiple organ systems. To determine the association between viral load and severity of CCHF infection, quantitative measurement of CCHF virus was performed using 1-step reverse-transcriptase polymerase chain reaction for 36 patients with CCHF infection. Viral loads ranged from 1.1x10(3) copies/mL to > or = 9.9x10(9) copies/mL. Nine (25%) of 36 patients died. In 8 of the 9 patients with fatal outcomes, viral loads were detected that were > or = 1x10(9) copies/mL, whereas in 25 of the 26 patients with nonfatal outcomes, viral loads were detected that were < 1x10(9) copies/mL (P<.001). A viral load > or = 1x10(9) RNA copies/mL can be considered to predict a fatal outcome with a positive predictive value of 80%, with 88.9% sensitivity and 92.6% specificity. We suggest that viral load is a measure of the severity of CCHF.

Fever of unknown origin: analysis of 71 consecutive cases.

BACKGROUND: Fever of unknown origin (FUO) is still an important problem in clinical practice. Evaluation of patient characteristics may clarify the utility of diagnostic tests and etiologies of FUO. METHODS: Fever of unknown origin in 71 patients was investigated at Ankara Numune Education and Research Hospital in Turkey between February 2001 and December 2004. RESULTS: Mean hospital stay and fever duration was 20.5 days and 44 days, respectively. Etiologies of FUO were as follows: infections 32 (45.1%), collagen vascular disease 19 (26.8%), neoplasm 10 (14.1%), and miscellaneous diseases 4 (5.6%). Diagnosis remained obscure in 6 patients (8.5 %). Tuberculosis was found to be 40% of the infectious causes of FUO. Mean hospital stay and fever duration were prolonged in infectious cases. Female predominance was observed in collagen vascular diseases (P = 0.047). Splenomegaly and lymphadenopathy were common in the neoplasm group (P = 0.017, P = 0.017, respectively). Erythrocyte sedimentation rate, aspartate aminotransferase, alanine aminotransferase and lactate hydrogenase levels were elevated in patients with collagen vascular diseases. Nine (12.7%) patients died during the follow-up period. CONCLUSIONS: Hospital stay and fever duration were prolonged in the infectious group of FUO patients. Infectious diseases, particularly tuberculosis, were the most important cause of FUO in our series. Tuberculosis should be kept in mind as an important etiology of FUO countries where tuberculosis is endemic.