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Introduction The efficacy of immune checkpoint inhibitors (ICIs) against malignant melanoma and numerously solid tumors has been demonstrated in several clinical studies. The incidence of immune-related adverse effects (irAEs) has increased after the rapidly expanding indications and clinical applications of ICIs. We present a case of nivolumab and ipilimumab-induced encephalitis with rapidly worsening consciousness and full recovery following ICIs suspension and high-dose steroid coupled with intravenous immunoglobulin (IVIG). Case Report A 67-year-old woman was diagnosed with stage 4 BRAF wild malignant melanoma with metastasis to the axillary and mediastinal lymph nodes. Beyond progression with dacarbazine, ipilimumab and nivolumab combination were administered at the second-line treatment of metastatic setting. A week after the first cycle patient was reported to have a fever of more than 38°C. Subacute cognitive impairment including mild changes in behavior was reported on the third day of fever. She suddenly developed confusion, dysarthria, and motor dysfunction a few days later. Due to the altered mental status accompanied by fever, lumbar puncture was performed with a pre-diagnosis of encephalitis, meningitis, and leptomeningeal carcinomatosis. Management & Outcome After excluding viral and autoimmune encephalitis, high-dose methylprednisolone was administered in addition to IVIG for 5 days with the diagnosis of immunotherapy-related encephalitis according to the recommendations for the management of irAEs. On the second day of the treatment patient's neurological status improved gradually. Discussion Being aware of symptoms of serious neurological irAEs associated with ICIs can prevent complications and improve survival.

Amaç: Kan dolaşımı infeksiyonları febril nötropenik hastalarda, ciddi morbidite ve mortalite ile seyretmektedir. Farklı merkezler arasında ve aynı merkezde yıllar içerisinde bakteriyemi epidemiyolojisi ve risk faktörleri değişiklikler göstermektedir. Bu çalışmanın amacı Kasım 2007-Kasım 2008 tarihleri arasında Ankara’da bir üniversite hastanesinde bakteriyemi sıklığını, risk faktörlerini ve epidemiyolojisini belirlemektir.Gereç ve Yöntemler: Çalışmamızda 115 hematolojik maligniteli hastada gelişen 177 febril nötropeni atağı ve 108 kan dolaşımı enfeksiyonu incelenmiştir. Olgular kan dolaşımı enfeksiyonu gelişen, kontrol grup ise gelişmeyen hasta grubu olarak tanımlanmıştır. Olgular ve kontroller risk faktörleri, komplikasyonlar ve mortalite oranları yönünden karşılaştırılmış; izole edilen mikroorganizmalar ve duyarlılık paternleri incelenmiştir.Bulgular: Epizodlarının %61’inde bakteriyemi gelişmiş, bunların %42.6’sı kateterle ilişkili bulunmuş ve atak ilişkili mortalite hızı %12.4 saptanmıştır. Altta yatan malignitesi kontrol altında olmayan, uzun süreli derin nötropenisi olanlarda bakteriyemi daha yüksek oranda izlenmiştir. Kök hücre nakil ünitesinde yatmak, altta yatan malignite tanıları, nakil uygulama türünden bağımsız olarak kök hücre nakli varlığı, malignite evresi, santral venöz kateter, mukozit ve ishal varlığı kan dolaşımı enfeksiyonu gelişimi ile ilişkili bulunmuş; altta yatan malignite evresi ve santral venöz kateter varlığı bağımsız risk faktörleri olarak tanımlanmıştır. En sık etkenleri olarak gram-pozitif bakteriler (%76.8); bunlar içinde de en sık koagülaz negatif stafilokoklar (%63.6) saptanmıştır. Metisilin direnci koagülaz negatif stafilokoklarda %64 bulunmuştur. Gram-negatif bakteriler içerisinde ise en sık Escherichia coli izole edilmiştir. Escherichia coli izolatlarında kinolon direnci %82.1 saptanmıştır.Sonuç: Sonuç olarak febril nötropenik hastalarda kan dolaşımı enfeksiyonu sıklığının, risk faktörlerinin ve epidemiyolojisinin izlemi, her merkezin kendi empirik tedavi yaklaşımını belirleyebilmesi için önemlidir., Aim: Bacteremia is considered as the most significant cause of mortality and morbidity in febrile neutropenic patients. The epidemiology and risk factors might differ among institutions and over the time period. The aim of this study is to evaluate the frequency, epidemiology and factors predictive of bacteremia in neutropenic patients in a university hospital in Ankara between November 2007 and November 2008.Material and Methods: 177 febrile neutropenic episodes of 115 patients with hematological malignancies were included in this study. Cases were defined as patients with bloodstream infection and controls were the patients without bloodstream infections. We evaluated the cases and controls for the risk factors, complications and mortality rates. Microorganisms isolated from blood samples and their susceptibility patterns were also analysed.Results: The prevalence of bacteremia was 61%, 42.6% of them were catheter related and mortality rate was 12.4%. Bloodstream infections are more common in the patients with uncontrolled underlying disease and long term severe neutropenia. Duration of severe neutropenia (neutrophile count

Background:This study aimed to evaluate the impact of tocilizumab treatment on clinical improvement in severe COVID-19 cases and the factors affecting clinical response.Methods:This single-center, retrospective, descriptive study was conducted on severeCOVID-19 patients. The ordinal scale of clinical status scores on the 0th, 1st, 3rd, and 7th days of tocilizumab treatment was calculated and compared for each patient. The ordinal scale of clinical status scores calculated on different days for the same patient was compared with Wilcoxon tests. The correlation between the clinical score and some laboratory parameters was evaluated by Pearson correlation analysis. Patients were grouped as responders and non-responders and compared by logistic regression analysis.Results:Forty-two patients were enrolled in the study. The median of the ordinal scale of clinical status scores on the 0th, 1st, 3rd, and 7th days of tocilizumab treatment were 6 (5 to 6), 6 (5 to 6), 6 (5 to 6), and 5 (4 to 7), respectively. When the clinical status scores on the 0 to 7 days of tocilizumab treatment were compared, the difference was statistically significant (p = 0.024, Wilcoxon). There was no statistically significant difference between day 0 and day 1 (p=0.317, Wilcoxon), day 0 and day 3 (p=0.467, Wilcoxon). By multivariate analysis, we determined that age ( OR: 0.91, 95% 0.84-0.98) and respiratory rate (OR:0.78, 95% 0.62-0.98) were factors affecting the response of tocilizumab treatment. No relationship was detected between laboratory parameters before tocilizumab treatment, including IL-6 levels and clinical response (p=0.756, Mann Whitney-U).Conclusion:The use of tocilizumab in younger patients with low oxygen support increases the chance of clinical response after treatment. Since the effect of laboratory parameters in predicting the clinical response of tocilizumab is limited, treatment indications should be determined based on clinical parameters.

Background/aim Pneumonia is the most serious clinical presentation of COVID-19. This study aimed to determine the demographic, clinical, and laboratory findings that can properly predict COVID-19 pneumonia. Materials and methods This study was conducted in the Gazi University hospital. All hospitalized patients with confirmed and suspected SARS-CoV-2 infection between 16 March 2020 and 30 April 2020 were analyzed retrospectively. COVID-19 patients were separated into two groups, pneumonia and nonpneumonia, and then compared to determine predicting factors for COVID-19 pneumonia. Variables that had a P-value of less than 0.20 and were not correlated with each other were included in the logistic regression model. Results Of the 247 patients included in the study 58% were female, and the median age was 40. COVID-19 was confirmed in 70.9% of these patients. Among the confirmed COVID-19 cases, 21.4% had pneumonia. In the multivariate analysis male sex (P = 0.028), hypertension (P = 0.022), and shortness of breath on hospital admission (P = 0.025) were significant factors predicting COVID-19 pneumonia. Conclusion Shortness of breath, male sex, and hypertension were significant for predicting COVID-19 pneumonia on admission. Patients with these factors should be evaluated more carefully for diagnostic procedures, such as thorax CT.

OBJECTIVE: To evaluate the rate of pneumococcal pneumonia (PP) among patients with community-acquired pneumonia (CAP) in Turkey and to investigate and compare features of PP and non-PP CAP patients. MATERIAL AND METHODS: This multicenter, non-interventional, prospective, observational study included adult CAP patients (age = 18 years). Diagnosis of PP was based on the presence of at least 1 positive laboratory test result for Streptococcus pneumoniae (blood culture or sputum culture or urinary antigen test [UAT]) in patients with radiographic findings of pneumonia. RESULTS: Four hundred sixty-five patients were diagnosed with CAP, of whom 59 (12.7%) had PP. The most common comorbidity was chronic obstructive pulmonary disease (30.1%). The mean age, smoking history, presence of chronic neurological disease, and CURB-65 score were significantly higher in PP patients, when compared to non-PP patients. In PP patients, 84.8% were diagnosed based ony on the UAT. The overall rate of PP patients among CAP was calculated as 22.8% considering the UAT sensitivity ratio of 63% (95% confidence interval: 45-81). The rate of intensive care treatment was higher in PP patients (P =.007). While no PP patients were vaccinated for pneumococcus, 3.8% of the non-PP patients were vaccinated (P =.235). Antibiotic use in the preceding 48 hours was higher in the non-PP group than in the PP group (31.8% vs. 11.1%, P =.002). The CURB-65 score and the rate of patients requiring inpatient treatment according to this score were higher in the PP group. CONCLUSION: The facts that PP patients were older and required intensive care treatment more frequently as compared to non-PP patients underline the burden of PP., Pfizer Pharmaceuticals, Turkey, This work was supported by Pfizer Pharmaceuticals, Turkey.

This study aimed to detect carbapenemase genes and to determine the in vitro susceptibility of Ceftazidime-Avibactam (CZA) in Enterobacterales isolates. Carbapenemase genes were detected by polymerase chain reaction. CZA sensitivity of isolates was evaluated with broth microdilution (BMD) and disk diffusion methods. A total of 318 carbapenem-resistant Enterobacterales isolates were included. Most of the isolates (n = 290, 91.2%) were identified as Klebsiella pneumoniae. The most common carbapenemase type was OXA-48 (n = 82, 27.6%). CZA susceptibility was evaluated in 84 isolates with OXA-48 and KPC carbapenemase activity. Both BMD and disk diffusion methods revealed that 95.2% of the isolates were sensitive to CZA; whereas, 4 (4.76%) isolates were resistant to CZA. Among colistin resistant isolates, 96.5% (n = 80) of them were susceptible to CZA. Our study demonstrated high in vitro efficacy of CZA in Enterobacterales isolates producing OXA-48 carbapenemase. High susceptibility rates against colistin resistant isolates which generally are also pan drug resistant, makes CZA a promising therapeutic choice for difficult-to-treat infections. Due to its high correlation with the BMD, disk diffusion method is a suitable and more practical method in detecting CZA in vitro activity.

AIMS: This study aimed to investigate the clinical and chest computed tomography (CT) features associated with clinical parameters for coronavirus disease (COVID-19) in the capital of Turkey, Ankara. MATERIALS AND METHODS: Epidemiological, clinical features, laboratory findings and radiological characteristics of 1563 hospitalised patients with COVID-19 in Ankara were collected, reviewed and analysed in this study. The risk factors associated with disease severity were investigated. RESULTS: Non-severe (1214; 77.7%) and severe cases (349; 22.3%) were enrolled in the study. Compared with the non-severe group, the severe group were significantly older and had more comorbidities (ie, hypertension, diabetes mellitus, cardiovascular disease and chronic kidney disease). Smoking was more common in the severe group. Severe patients had higher respiratory rates and higher incidences of cough and dyspnoea compared with non-severe patients. Compared with the non-severe patients, the severe patients had increased C-reactive protein (CRP), procalcitonin, neutrophil to lymphocyte ratio (NLR) and CRP/albumin ratio and decreased albumin. The occurrence rates of consolidation, subpleural sparing, crazy-paving pattern, cavity, halo sign, reversed halo sign, air bronchogram, pleural thickening, micronodule, subpleural curvilinear line and multilobar and bilateral involvement in the CT finding of the severe patients were significantly higher than those of the non-severe patients. CONCLUSIONS: Many factors are related to the severity of COVID-19, which can help clinicians judge the severity of the patient and evaluate the prognosis. This cohort study revealed that male sex, age (≥55 years), patients with any comorbidities, especially those with cardiovascular disease, dyspnoea, increased CRP, D-dimer and NLR, and decreased lymphocyte count and CT findings of consolidation and multilobar involvement were predictors of severe COVID-19.

This article aims to give practical information and concrete suggestions on what should be considered in emergency, semi-urgent and elective settings for common anorectal diseases in the hectic period of the COVID-19 pandemic, based on early results of a series of anorectal interventions.Referring to other related guidelines, general considerations specific to the diagnosis and treatment of highly prevalent anorectal diseases were developed to target the correct patients, evaluate and orientate by telemedicine, adapt the Proctology Unit to the new pandemic, and control contamination and infection. Specific considerations for common anorectal diseases were cited, and our initial results were retrospectively documented.From March 1 to April 10, 2020, we contacted 240 patients with anorectal diseases in two centers. We evaluated the results retrospectively on 16-17 April. At the end of this survey, 14 patients (5.8%) were lost for further contact and follow-up. Thirty-one patients (12.9%) were evaluated as nondeferrable cases and invited to the Proctology Unit. Twenty-eight patients required interventions at the same session. Adhering to the principles described here, more than 90 percent of benign anorectal disorders could be treated successfully, with 2.1 percent of suspected contamination and no confirmed cases. None of the Proctology personnel or their close contacts developed COVID-19, either.By adhering to the principles outlined in this practical guide, it was possible to treat most of the benign anorectal diseases safely in the initial, hectic period of the COVID-19 pandemic.

Purpose Cytokines are major mediators of COVID-19 pathogenesis and several of them are already being regarded as predictive markers for the clinical course and outcome of COVID-19 cases. A major pitfall of many COVID-19 cytokine studies is the lack of a benchmark sampling timing. Since cytokines and their relative change during an infectious disease course is quite dynamic, we evaluated the predictive value of serially measured cytokines for COVID-19 cases. Methods In this single-center, prospective study, a broad spectrum of cytokines were determined by multiplex ELISA assay in samples collected at admission and at the third day of hospitalization. Appropriateness of cytokine levels in predicting mortality were assessed by receiver-operating characteristic (ROC) analyses for both sampling times in paralel to conventional biomarkers. Results At both sampling points, higher levels of IL-6, IL-7, IL-10, IL-15, IL-27 IP-10, MCP-1, and GCSF were found to be more predictive for mortality (p Conclusion Our study results suggest that single-sample-based cytokine analyzes can be misleading and that cytokine levels measured serially at different sampling times provide a more precise and accurate estimate for the outcome of COVID-19 patients.

Micafungin was shown to be as efficacious as caspofungin in treating patients with candidaemia and invasive candidiasis (IC). However, it remains unknown if micafungin or caspofungin is a cost-effective definitive therapy for candidaemia and IC in Turkey. The present study aimed to determine the economic impact of using micafungin versus caspofungin for treatment of candidaemia and IC in the Turkish setting. A decision analytic model was constructed and was populated with data (i.e. transition probabilities, duration of initial antifungal treatment, reasons for treatment failure, percentage of patients who stepped down to oral fluconazole, and duration on oral fluconazole) obtained from a published randomised clinical trial. Cost inputs were derived from the latest Turkish resources while data that were not readily available in the literature were estimated by expert panels. One-way sensitivity analyses, threshold analyses, scenario analyses and probabilistic sensitivity analyses were conducted. Caspofungin (a,notsign2693) incurred a lower total cost than micafungin (a,notsign4422), with a net cost saving of a,notsign1729 per treated patient. Drug acquisition cost was the main cost driver for both study arms. The model outcome was robust over wide variations (of +/- 100.0% from the base case value) for all input parameters except for micafungin drug cost and the duration of initial treatment with micafungin. Caspofungin appears to be a cost-saving option in treating candidaemia and IC from the Turkish hospital perspective.

In this article, we report a case of a 25-year-old male patient who was under follow-up for nephrolithiasis and repeated urological interventions. His last operation was carried out 9 months ago for insertion of a double-J catheter. Pseudomonas aeruginosa, which is susceptible to only colistin treatment, was detected in the urine culture. Before the removal of the double-J catheter, colistin and ceftazidime antibiotics were started to prevent the risk of bloodstream infection. However, the treatment was stopped urgently due to signs of nephrotoxicity. His treatment was restarted with colistin 300 mg once as the initial loading dose, followed by 150 mg/day. However, this time, colistin neurotoxicity has developed and the treatment was again stopped. Meropenem 6 g/day, gentamicin 2 mg/kg and rifampicin 300 mg were prescribed. Negative urine culture was achieved on the fifth day of treatment.

Background This article aims to give practical information and concrete suggestions on what should be considered in emergency, semi-urgent and elective settings for common anorectal diseases in the hectic period of the COVID-19 pandemic, based on early results of a series of anorectal interventions. Methods Referring to other related guidelines, general considerations specific to the diagnosis and treatment of highly prevalent anorectal diseases were developed to target the correct patients, evaluate and orientate by telemedicine, adapt the Proctology Unit to the new pandemic, and control contamination and infection. Specific considerations for common anorectal diseases were cited, and our initial results were retrospectively documented. Results From March 1 to April 10, 2020, we contacted 240 patients with anorectal diseases in two centers. We evaluated the results retrospectively on 16-17 April. At the end of this survey, 14 patients (5.8%) were lost for further contact and follow-up. Thirty-one patients (12.9%) were evaluated as nondeferrable cases and invited to the Proctology Unit. Twenty-eight patients required interventions at the same session. Adhering to the principles described here, more than 90 percent of benign anorectal disorders could be treated successfully, with 2.1 percent of suspected contamination and no confirmed cases. None of the Proctology personnel or their close contacts developed COVID-19, either. Conclusion By adhering to the principles outlined in this practical guide, it was possible to treat most of the benign anorectal diseases safely in the initial, hectic period of the COVID-19 pandemic.

Pneumococcal diseases, including pneumonia with or without bacteremia, remain an important cause of morbidity and mortality in adults, especially among the elderly and those with certain medical conditions, including immunocompromising conditions all over the world. Two pneumococcal vaccines are currently licensed for adults in Turkey, 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23). PPSV23 has been available for many years for use in adults. A 7-valent pneumococcal conjugate vaccine (PCV7) included in the Expanded Programme on Immunization for use in infants and children in 2008, and thereafter PCV13 replaced PCV7 in 2011. Recently, the Ministry of Health of Turkey accepted risk groups for vaccine-preventable diseases, and implemented their immunization schedules in accordance with the decisions of Immunization Advisory Committee, including adult pneumococcal vaccination greatly compatible with those of updated U.S. Advisory Committee on Immunization Practices (ACIP) recommendations such as PCV13 for selected high-risk adults and for all adults >= 65 years of age. Furthermore, surveillance of invasive pneumococcal disease has already been included as part of the Surveillance of Vaccine-Preventable Invasive Bacterial Diseases announced that would be started soon in Turkey. In this consensus report prepared by Study Group for Adult Immunization of the Turkish Society of Clinical Microbiology and Infectious Diseases, relevant literature and international recommendations were reviewed, and recommendations agreed are presented. Examples of some selected recommendations are as follows: [1] All individuals aged >= 65 years should receive PCV13 followed by PPSV23, as well as adults of any age with the high-risk conditions (ie, patients with an immunocompromising condition, functional or anatomic asplenia, a cerebrospinal fluid leak, and a cochlear implant). [2] Pneumococcal vaccination is also recommended for adults = 1 year after PCV13 for most immunocompetent adults, it should be administered >= 8 weeks later for high-risk patients. [5] In patients who have already received PPSV23, >= 1 year should elapse before they are given PCV13. [6] For immunocompromised and asplenic patients, a booster dose of PPSV23 is recommended >= 5 years after the first dose. [7] A booster dose of PCV13 is not recommended for any age group. [8] Both vaccines may be administered concurrently with influenza vaccine, but at a separate site. [9] Use of PCV13 in adults may not always provide expected benefit because of the trend for vaccine strains to disappear from the population following childhood immunization with same vaccine. Therefore, surveillance for adult pneumococcal diseases is highly important to understand local epidemiology including serotype distribution and antibiotic resistance rates.

Micafungin was reported to be non-inferior to liposomal amphotericin B (LAmB) in treating patients with candidaemia and invasive candidiasis (IC). The current study aimed to evaluate the economic impact of using micafungin versus LAmB for treatment of candidaemia and IC in Turkey. A decision analytic model, which depicted economic consequences upon administration of micafungin or LAmB for treating patients with candidaemia and IC in the Turkish hospitals, was constructed. Patients were switched to an alternative antifungal agent if initial treatment failed due to mycological persistence. All patients were followed up until treatment success or death. Outcome probabilities were obtained from published literature and cost inputs were derived from the latest Turkish resources. Expert panels were used to estimate data that were not available in the literature. Cost per patient treated for each intervention was then calculated. Sensitivity analyses including Monte Carlo simulation were performed. For treatment of candidaemia and IC, micafungin ((sic)4809) was associated with higher total cost than LAmB ((sic)4467), with an additional cost of (sic)341 per treated patient. Cost of initial antifungal treatment was the major cost driver for both comparators. The model outcome was robust over a wide variation in input variables except for drug acquisition cost and duration of initial antifungal treatment with micafungin or LAmB. LAmB is cost-saving relative to micafungin for the treatment of candidaemia and IC from the Turkish hospital perspective, with variation in drug acquisition cost of the critical factor affecting the model outcome.

Summary Anidulafungin has been shown to be non-inferior to, and possibly more efficacious, than fluconazole in treating patients with invasive candidiasis (IC). This study aimed to determine the cost-effectiveness of anidulafungin vs fluconazole for treatment of IC in the Turkish setting. A decision analytic model was constructed to depict downstream economic consequences of using anidulafungin or fluconazole for treatment of IC in the Turkish hospitals. Transition probabilities (ie treatment success, observed or indeterminate treatment failures) were obtained from a published randomised clinical trial. Cost inputs were from the latest Turkish resources. Data not available in the literature were estimated by expert panels. Sensitivity analyses were performed to assess the robustness of the model outcome. While anidulafungin [TL 17 171 (USD 4589)] incurred a higher total cost than fluconazole [TL 8233 (USD 2200) per treated patient, treatment with anidulafungin was estimated to save an additional 0.58 life-years, with an incremental cost-effectiveness ratio of TL 15 410 (USD 4118) per life-years saved. Drug acquisition cost and hospitalisation were the main cost drivers for anidulafungin and fluconazole arms respectively. The model findings were robust over a wide range of input variables except for anidulafungin drug cost. Anidulafungin appears to be a cost-effective therapy in treating IC from the Turkish hospital perspective.

Invasive fungal infections (IFIs) are a major concern within healthcare systems. This pharmacoeconomic study evaluated the use of caspofungin (CAS) versus liposomal amphotericin B (L-AmB) in the empirical treatment of IFIs within the Turkish healthcare system. A decision-analytic model was adopted, utilising data from a randomised, non-inferiority clinical trial and a panel of clinical experts in Turkey. A five-point composite outcome measure was used to evaluate both agents. Sensitivity analyses were performed. In the base-case scenario, CAS was preferred over L-AmB by Turkish Lira (TL) 3961 per patient treated, TL 12 904 per successfully treated patient and TL 3972 per death averted. One-way sensitivity analysis did not change the study outcome. Monte Carlo simulation concluded a 71.0% chance of the outcome favouring CAS. The results were most sensitive to changes in length of stay. This is the first economic evaluation of the empirical treatment of IFIs in Turkey and suggests that CAS is more cost effective than L-AmB. (C) 2013 Elsevier B. V. and the International Society of Chemotherapy. All rights reserved.

Pneumococcal disease is responsible for significant morbidity and mortality. All over the world, 1.6 million people die of pneumococcal disease every year; this estimate includes the deaths of 1 million children aged less than 5 years and the deaths of 600.000- 800.000 adults. The burden of pneumococcal disease is high in adults. Increasing age and the presence of comorbidity has a significant affected of the risk of developing the disease. During mass gatherings, such as pilgrimage individuals, is exposed to severe community-acquired pneumococcal infections. Individuals who has Streptococcus pneumoniae in nasopharynx, have the potential to infection and leave exposed to the risk of pneumococcal disease the other Individuals with sneezing, coughing or out of breath, given breath through droplets of these microorganisms. In the present review, the relationship of pneumococcal disease in adults and pilgrimage, vaccination strategies will be considered and then during a visit to Pilgrimate and Umrah pilgrims against the current vaccine recommendations will be summarised.

Introduction: Recently, a decreased susceptibility to teicoplanin has been observed among coagulase-negative staphylococci (CNS) isolated from bloodstream infections in patients with hematological malignancies. In this study, we aimed to determine the minimum inhibitory concentrations (MIC) of teicoplanin, which is frequently used in the empirical treatment, and of a new agent, daptomycin, against CNS isolated from bloodstream infections. Materials and Methods: The study was performed on CNS strains isolated from bloodstream infections of patients with hematological malignancies during the period 2009-2011. Susceptibility to oxacillin was tested by disk diffusion method. Daptomycin and teicoplanin MIC were determined using the E-test method. Results: A total of 179 CNS strains causing bloodstream infections were studied. Among them, S. epidermidis (36.3%) and S. haemolyticus (35.2%) were the most frequent CNS species. The oxacillin resistance rate was found statistically higher among S. haemolyticus (61%) strains than among S. epidermidis (32%) (p= 0.001). Although teicoplanin and daptomycin resistance was not detected among the CNS isolates, two (1.1%) of the isolates demonstrated intermediate susceptibility to teicoplanin. Conclusions: S. haemolyticus and S. epidermidis were the major causes of bloodstream infections in patients with hematological malignancies. Oxacillin resistance was more frequent among S. haemolyticus isolates. Teicoplanin resistance was not detected among the CNS isolates. However, because two of the isolates demonstrated decreased susceptibility to teicoplanin, resistance rates to teicoplanin should be closely monitored. Daptomycin was found to be effective against both oxacillin-resistant and teicoplanin-intermediate CNS isolates.

Cutaneous aspergillosis is very rare and occurs predominantly in immunocompromised patients including transplant recipients. We report a 26-year-old male with acute lymphoblastic leukemia who developed cutaneous aspergillosis after undergoing combined immunosuppressive treatment including corticosteroid, cyclosporine A, mychophenolate mofetil and mesenchymal stem cells for steroid refractory skin acute graft versus host disease after myeloablative haematopoietic stem cell transplantation. The patient was treated with oral voriconazole therapy and recovered partially.

Influenza A H1N1 virus, causing a pandemic since spring 2009, has been an important cause of morbidity and mortality worldwide. Patients with hematological malignancies and hematopoietic stem cell transplant (HCT) recipients are in a high-risk group and might require hospitalization more commonly because of H1N1 infection. Early demonstration of H1N1 influenza virus and commencing antiviral therapy promptly can be life saving particularly in immunosuppressed patients. We retrospectively reviewed the data of 10 HCT recipients who were diagnosed with influenza H1N1 infection at the Stem Cell Transplantation Unit of Gazi University Hospital in Turkey, from October through December 2009. All patients, except 1, were started empirically on oseltamivir on admission, after nasopharyngeal and oropharyngeal sampling for H1N1 virus. Four of the patients, 2 of whom developed pneumonia, required hospitalization. One of the patients with pneumonia died of respiratory failure caused by bacterial co-infection. The course of the remaining patients was uneventful. In conclusion, HCT recipients infected with H1N1 during the influenza H1N1 pandemic did not necessarily have an adverse prognosis, particularly with prompt administration of the appropriate antiviral therapy.

Summary Objectives Invasive fungal infections (IFI) are a significant cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. Hepatosplenic candidiasis (HSC) is defined as a distinct form of invasive candidiasis, with liver, spleen, and kidney involvement, in patients with hematological disorders. Methods The charts of 255 patients (male/female 168/87; median age 35 (range 16–71) years) who were evaluated pre-HSCT at the Gazi University Hospital Stem Cell Transplantation Unit between 2003 and 2008, were retrospectively reviewed. Results HSC, which was demonstrated in six (2.3%) patients, was found to be more common in allogeneic HSCT recipients than in autologous HSCT recipients and in patients who had received two or more previous chemotherapy courses than in patients who had received fewer than two ( p >0.05). Patients with HSC tended to have a worse performance status than patients without HSC according to the World Health Organization ( p =0.001) and Karnofsky scale ( p =0.007). Pre-transplantation ferritin ( p =0.008) and acute phase reactant levels, including erythrocyte sedimentation rate ( p =0.025) and C-reactive protein ( p =0.007), were significantly higher in patients with HSC than in patients without HSC. Conclusions This study shows the predictive role of pre-transplantation ferritin levels in selecting a subset of patients at increased risk for HSC. Pre-transplantation risk assessment and targeted strategies might lower the morbidity and mortality of IFI in HSCT recipients.

Background Immune-compromised patients with latent TB infection (LTBI) are at risk for TB reactivation and should receive prophylaxis. Whereas the tuberculin skin test (TST) has limitations particularly in immune-compromised patients. Aims This retrospective study was conducted to determine the incidence of TB infection in adult HSCT recipients whose preventive therapy for LTBI was determined according to the guidance of targeted TST. Patients and methods Five hundred and fifty-eight consecutive HSCT recipients (287 autologous and 271 allogeneic) who survived ≥100 days post-transplantation were included in this analysis. Results Tuberculin skin test results were available in 493 of 558 transplants (88.3%). The incidence of negative TST was 54.5% (269 of 493 patients). One multiple myeloma patient with a history of TB and negative TST result and was not on INH prophylaxis developed reactivation of TB infection. None of the recipients under INH prophylaxis (151 of 558 transplants; 27.1%) and none of the 224 patients with TST ≥5 mm developed TB infection. Discussion Despite the limitations of being a retrospective analysis and variable prophylaxis thresholds of TST, there are some remarkable results of this analysis. We had no TB infection in the allogeneic HSCT recipients. The high incidence of negative TST results may be attributed to the underlying immune-deficiency. TST may not be a reliable guide for predicting TB reactivation risk in hematology patients. Conclusion Tuberculin skin test may have a high rate of false-negative and false-positive results in HSCT recipients. The general guidelines for targeted TST to guide treatment of LTBI may not apply to all regions and situations. More reliable methods are required to predict and treat LTBI in these specific conditions.

This study spreading over a span of eight months described Candida kefyr infections in hematolology patients from a Turkish University hospital. A total of 18 strains were isolated from various body locations of 18 patients. DNA fingerprinting of the isolates was performed by using randomly amplified polymorphic DNA (RAPD) method and karyotyping by pulsed-field get electrophoresis (PFGE). RAPD analysis of all the C. kefyr strains revealed that strains collected from 18 different patients exhibited seven different genotypes, while those were six in PFGE. Taken together, this is probably the first molecular survey of C. kefyr infections in the hematology unit documenting nosocomial transmission of C. kefyr isolates. (C) 2007 Elsevier Masson SAS. All rights reserved.

Mild anemia and leukopenia are the most common hematologic findings in the course of acute brucellosis. However severe form of thrombocytopenia is less frequently reported. The patient was admitted to the hospital with fever, gingival bleeding, and petechial skin lesions related to severe thrombocytopenia. He was investigated for the causes of thrombocytopenia. Test results showed that Wright agglutination test was positive at 1/5120 titer, and blood culture was positive for Brucella melitensis. Finally, he was diagnosed as acute brucellosis. Rifampicin and doxycycline treatment was started on he third day of admission. A bone marrow aspiration was performed on the seventh day of admission because of severe thrombocytopenia did not response to brucellosis treatment. The result of bone marrow aspiration was consistent with idiopathic thrombocytopenic purpura. With the addition of corticosteroid treatment, his complaints resolved immediately, and thrombocyte count rose to normal range. He was discharged on the 12th day of rifampicin and doxycycline therapy, and he was successfully completed 6-week therapy. In cases of brucella induced immune thrombocytopenia, corticosteroid treatment might be useful for the prevention of bleeding complications.

This is the last of a series of articles on invasive fungal infections prepared by opinion leaders in Turkey. The aim of these articles is to guide clinicians in managing invasive fungal diseases in hematological malignancies and stem cell transplantation based on the available best evidence in this field. The previous articles summarized the diagnosis and treatment of invasive fungal disease and this article aims to explain the risk categorization and guide the antifungal prophylaxis in invasive fungal disease.Bu makale Türkiye’de invazif fungal enfeksiyon ile uğraşan uzmanlar tarafından hazırlanan bir seri yazının sonuncusudur. Bu makaleler hematolojik malignitelerde ve kök hücre nakli hastalarında invazif fungal hastalıkların yönetimini eldeki kanıtların ışığında en iyi hale getirmeyi amaçlamaktadır. İlk yazılar tanı ve tedaviyi özetlerken, bu makale invazif fungal hastalıkta risk kategorizasyonu ve profilaksiyi ele almaktadır.

A systematic evaluation of the attributable mortality of Stenotrophomonas maltophilia bacteremia was undertaken in a matched, retrospective, case-control study. We determined the attributable mortality rate (26.7%) and mortality risk ratio (an 8-fold increase) of S. maltophilia bacteremia. The attributable mortality rate for S. maltophilia bacteremia is similar to the attributable mortality rate for other nosocomial bloodstream infections.

We report a breast cancer pa-tient with Sweet’s syndrome associated with herpessimplex infection.Case reportA 34-year-old woman was found to have infiltratingductal left breast carcinoma (T2N1M0) in March1999. Treatment modality included modified left rad-ical mastectomy, local regional radiation therapy andfive courses of adjuvant chemotherapy containing 5-fluorouracil, cyclophosphamide and doxorubicin. Shecould not receive a sixth course of chemotherapy be-301cause of neutropenia. In February 2001, progressivebone pain was shown to be caused by bone metastasisin the lumbar column and pelvis. She received radi-ation therapy to the T10-S1 and pelvis. One monthafterradiotherapy,shecomplainedoftypicalvesicularlesions for herpetic infection on her lips and thelesions then spread all over the face (Fig.1). The pa-tient’s temperature was 38aeC. Her hemoglobin was5.8g/dl and platelet count was 25.000/mm

Aim: We aimed to determine the relationship between teicoplanin use and increased minimal inhibitor concentrations of coagulase-negative staphylococci (CNS) isolated from catheter related bloodstream infections (CRBSI) in patients with hematological malignancies. Methods : The study was performed on CNS strains isolated from CRBSI of FN patients during the period between 2006-2010. Teicoplanin MICs were determined by using the Etest method. Demographic characteristics of patients, underlying hematological diseases, the dose and course of teicoplanin were recorded. Grams and international units of teicoplanin were further converted into defined daily doses (DDD). Results: A total of 72 CNS strains causing CRBSI isolated from FN attacks of the patients were analyzed. Among them, Staphylococcus. epidermidis (47%) and Staphylococcus haemolyticus (42%) were the most frequent CNS species. Oxacillin resistance was detected in 74% of all isolates. Increase in MIC values among CNS strains were detected in 44 patients (61%). Mean MIC value for teicoplanin among CNS strains before the treatment was 2.1±1.76 µg/ml, and it was 4.4±3.89 µg/ml after the treatment (p

Introduction of high-dose chemotherapy and the novel agents including bortezomib, Lenalidomide, and Thalidomide has provided a significant progress in the treatment of multiple myeloma (MM) with an increase in median overall survival up to 6-8 years. However, the advances in myeloma treatment comes at a price with new spectrum of treatment-related infectious complications which should be taken into consideration while treating these patients.We report here two patients with Ig G λ MM presenting with intracerebral mass lesions in the abscence of constitutional symptoms that would suggest an infectious etiology. Both patients had severe hypogammaglobulinemia and lymphopenia, which was attributed to treatment regimens including bortezomib. Intervention The surgical intervention-revealed abscess in both cases caused by Nocardia cyriacigeorgica, a relatively new pathogen which rarely causes infections in humans and also an unexpected pathogen in myeloma patients.Although every aspect of immune system is known to be affected in MM, humoral immune deficiency is the hallmark of the inherent immune defect in this disease. Introduction of the novel agents, bortezomib in particular seems to have changed the characteristics of the immune dysfunction and the spectrum of the opportunistic infections by causing qualitative and quantitative changes in cellular immunity. The new spectrum of infectious agents might not be limited to hepatitis B and herpes zoster. Monitoring lymphopenia and administration of prophylactic antimicrobial agents accordingly could be considered in patients treated with bortezomib.

We describe a case of cavitary pneumonia due to Candida dubliniensis along with fungemia due to Candida kefyr in a leukemic patient. This is the first case of C. dubliniensis isolated in our laboratory. The identification was performed by phenotypic and molecular methods such as thermotolerance test, carbohydrate fermentation and polymerase chain reaction.

Background Invasive fungal infections (IFI) are associated with considerable expense and mortality on healthcare systems. There is a need to provide evidence of both clinical efficacy and value for money with any health technology. The current pharmacoeconomic evaluation investigated the use of liposomal amphotericin B (LAmB) and voriconazole for the empiric treatment of IFI in the Turkish setting. Methods Decision analytic modelling was used to create a pathway for patient treatment with a 5-point composite outcome measure. The data was obtained from a major non-inferiority multicentre randomised controlled study, with an expert panel of clinicians in Turkey providing transition probabilities and cost not available in the literature. Sensitivity analyses were performed on the inputs from the clinical trial and the expert panel. Results As per the base case analysis, voriconazole was preferred by Turkish Lira (TL) 2,523 per patient treated and TL2,520 per surviving patient. LAmB was the preferred alternative by TL5,362 per successfully treated patient. Removing fever resolution as part of the composite outcome measure resulted in voriconazole being the preferred alternative per successfully treated patient. Univariate sensitivity analysis highlighted that increasing the duration of voriconazole by >1.2 days or decreasing LAmB by >1.0 days changes the result. Monte Carlo Simulation resulted in 69.4% of simulations favouring voriconazole per patient treated. Conclusion There is a strong likelihood that voriconazole is economically more favourable than LAmB in the empiric treatment of IFI in Turkey.

Brucellosis may be seen in any age group, but it still involves young and middle aged adults more frequently. Our aim was to investigate the relationship between age and the duration of disease on clinical findings of brucellosis in adults in this study. One hundred and sixty-three patients with brucellosis, treated in our hospital, between 1997 and 2003, were evaluated retrospectively. Fever was found in 60.7% of the patients, and it was significantly higher when the duration of disease was less than one month (p = 0.03). Fever was significantly lower in the ≥ 65 age group (p = 0.01). Sacroiliitis was detected in 44.1% of patients. Sacroiliitis was significantly higher in the 15–35 age group (p = 0.03). There were no differences between age groups and other clinical and laboratory findings. Sacroiliac involvement was noted particularly in young adults who manifested lumbar pain and fever, but this might not be a major symptom of brucellosis in the elderly, or in patients showing symptoms for more than a month.

Increasing use of more aggressive treatment approaches in patients with hematologic malignancies leads to an increased frequency of invasive fungal infections, which is a major cause of transplant-related mortality in hematopoietic stem cell recipients. In this respect, the presence of an active fungal infection prior to transplantation may hinder subsequent hematopoietic stem cell transplantation (HSCT); which sometimes is the only curative treatment. We report here the results of 13 consecutive patients transplanted with active fungal infection. Thirteen patients (7 males and 6 females) with a median age of 34 years (range, 16-53 years) underwent 15 HSCT between September 2003 and April 2007. In this group of 15 patients, consisting of hematologic malignancies with high risk of relapse or severe aplastic anemia, 11 (73%) transplants performed in subjects with active invasive fungal infection (IFI) patients survived 30 days after transplantation. Three patients (1 patient with primary disease relapse, 1 patient with graft versus host disease [GVHD] complicated with fungal pneumonia, and 1 patient with severe sinusoidal obstruction syndrome and GVHD complicated with aspiration pneumonia) died on days +66, +74, and +62 posttransplantation, respectively, within the first 100 days of HSCT. After a median follow-up time of 306 days (range, 145-680 days), four of 13 (31%) patients with active IFI were alive and disease free. Among a population of HSCT recipients with a dismal prognosis without transplantation, performing the procedure despite active IFI saved a considerable proportion of the patients. The presence of active IFI did not seem to be an absolute contraindication for HSCT, particularly among high-risk patients in whom a treatment delay could be fatal.

We describe a case in which a patient immunocompromised by acute myeloid leukemia experienced acute fulminating invasive fungal sinusitis followed by pneumonia and then death. Though the microbiology of the pneumonia could not be directly investigated, nasal lesions revealed fungal mycelium. Valsa sordida was consistently cultured from a biopsied sample. The fungus was identified to the genus level based on morphology in culture and DNA sequence homology, and then was placed at species level by means of phylogenetic analysis of the nuclear ribosomal internal transcribed spacer region. The fungus is in the order Diaporthales, family Valsaceae in the Ascomycota and is distributed worldwide as a pathogen of trees in the genera Populus and Salix. Koch's postulates were demonstrated to apply in a neutropenic rat model. The fungus was susceptible to antifungals with MIC-0 scores of 0.0313 microg/ml for amphotericin B, 0.25 microg/ml for voriconazole, 0.0313 microg/ml for caspofungin, and MIC-2 of 16 microg/ml for fluconazole. This is the first substantiated report of an isolate in the genus Valsa (anamorph Cytospora) being identified in human disease.