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Objective: Skull base osteomyelitis (SBO) is a rare, life-threatening infection and frequently followed and treated by otolaryngologists previously. In this study, we analyzed the diagnosis, treatment and long-term outcomes of SBO from the perspective of infectious diseases and clinical microbiology (IDCM). Methods: Hospitalized patients with SBO between 2012-2019 were evaluated retrospectively. Epidemiological, clinical, laboratory data of the patients were recorded. The patients who recovered with and without sequelae were compared. Results: The mean age of 16 SBO cases was 66 years, 75% of them were male and 87.5% had diabetes mellitus (DM). Cranial nerve and vascular/dural involvement were present in 75% and 56.3% of them, respectively. The most common isolated microorganism were P. aeruginosa, staphylococci and Candida spp. 81.2%, 43.7%, and 56% of the patients received anti-pseudomonal antibiotics, additional glycopeptide and additional antifungal drugs, respectively. The sequelae rate was 46.7% in a 24-month follow-up. Hypertension (p=0.041), duration of complaints (p=0.003), bilateral involvement of skull base (p=0.001), vascular thrombosis/inflammation or dural involvement (p=0.007), previous surgical intervention (p=0.041) and elevated ESR at the end of treatment (p=0.014) were defined as risk factors for permanent sequelae. There was no in-hospital mortality. Conclusions: SBO mainly affects older male patients with DM and causes significant sequelae in half of them. In the cases unresponsive to anti-pseudomonal agents, the addition of antifungal therapy empirically may provide a clinical response. Permanent sequelae are more common in cases with delayed diagnosis/treatment, bilateral, vascular or dural involvement, and elevated ESR at the end of treatment. ESR can be used to determine the treatment response and duration. The follow-up and treatment of SBO cases by IDCM with the support of experienced surgeons may contribute to the positive clinical results. [ABSTRACT FROM AUTHOR]

[Display omitted] • Tocilizumab, anakinra and prednisolone did not affect the antibody response to SARS-CoV-2. • The antibody response correlated with and could be predicted by involvement on thoracic CT. • The antibody level also correlated with the level of lung involvement on thoracic CT. Disease severity, previous medications and immunosuppressive agents could affect the antibody response against SARS-CoV-2. This study aimed to analyze variables affecting the humoral response to SARS-CoV-2. This prospective cohort study included adult patients who recovered from COVID-19 and were admitted to a COVID-19 follow-up unit. Eight patient groups were defined in accordance with the results of thoracic computed tomography (CT), SARS-CoV-2 PCR test, and tocilizumab or anakinra use during active disease. Anti-S IgG antibodies were determined by ELISA in serum samples. Anti-S positive and negative cases were compared. A total of 518 patients were included in the study. SARS-CoV-2 IgG antibodies were positive in 82.8% of patients. SARS-CoV-2 PCR positivity, extent of lung involvement on CT, and time to antibody testing were independently associated with antibody positivity. Tocilizumab, anakinra or prednisolone use was not a factor affecting the antibody response. The rate of antibody response and sample/CO values among antibody-positive patients showed a linear relationship with the extent of lung involvement on CT. The use of tocilizumab, anakinra and prednisolone for COVID-19 did not affect the antibody response against SARS-CoV-2. The main driver of antibody response among patients with COVID-19 was the extent of pulmonary involvement on CT. [ABSTRACT FROM AUTHOR]

Background: There is limited evidence on the modification or stopping of antiretroviral therapy (ART) regimens, including novel antiretroviral drugs. The aim of this study was to evaluate the discontinuation of first ART before and after the availability of better tolerated and less complex regimens by comparing the frequency, reasons and associations with patient characteristics. Methods: A total of 3019 ART-naive patients registered in the HIV-TR cohort who started ART between Jan 2011 and Feb 2017 were studied. Only the first modification within the first year of treatment for each patient was included in the analyses. Reasons were classified as listed in the coded form in the web-based database. Cumulative incidences were analysed using competing risk function and factors associated with discontinuation of the ART regimen were examined using Cox proportional hazards models and Fine-Gray competing risk regression models. Results: The initial ART regimen was discontinued in 351 out of 3019 eligible patients (11.6%) within the first year. The main reason for discontinuation was intolerance/toxicity (45.0%), followed by treatment simplification (9.7%), patient willingness (7.4%), poor compliance (7.1%), prevention of future toxicities (6.0%), virologic failure (5.4%), and provider preference (5.4%). Non-nucleoside reverse transcriptase inhibitor (NNRTI)-based (aHR = 4.4, [95% CI 3.0–6.4]; p < 0.0001) or protease inhibitor (PI)-based regimens (aHR = 4.3, [95% CI 3.1–6.0]; p < 0.0001) relative to integrase strand transfer inhibitor (InSTI)-based regimens were significantly associated with ART discontinuation. ART initiated at a later period (2015-Feb 2017) (aHR = 0.6, [95% CI 0.4–0.9]; p < 0.0001) was less likely to be discontinued. A lower rate of treatment discontinuation for intolerance/toxicity was observed with InSTI-based regimens (2.0%) than with NNRTI- (6.6%) and PI-based regimens (7.5%) (p < 0.001). The percentage of patients who achieved HIV RNA < 200 copies/mL within 12 months of ART initiation was 91% in the ART discontinued group vs. 94% in the continued group (p > 0.05). Conclusion: ART discontinuation due to intolerance/toxicity and virologic failure decreased over time. InSTI-based regimens were less likely to be discontinued than PI- and NNRTI-based ART. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the comorbidities, antiretroviral therapy (ART) switches, and drug side-effects in HIV-infected patients who were followed in the Department of Infectious Diseases and Clinical Microbiology, Istanbul Faculty of Medicine, Istanbul University. Methods: This study was designed as a retrospective cohort study. Files of HIV-infected patients admitted to the outpatient clinic between years 2002 and 2018 were evaluated. Among them, 210 patients over 18 years of age, whose HIV/AIDS diagnosis was confirmed with ELISA and Western Blot test, without loss to follow up longer than six months, and using ART for at least 6 months were included in the study. Their demographic and clinical features, laboratory results, initial ART regimen, and its side-effects, reasons for ART switches, and subsequent ART regimen were recorded. Results: 165 (78.5%) out of 210 patients were men, and 45 (21.4%) patients were women. Mean age of the patients was 40.4±12.373. 152 (72.4%) patients identified themselves as heterosexual, and 39 (18.6%) were men who had sex with men. Comorbidities of patients during their follow-up were hyperlipidemia in 42 (20%), hypertension in 22 (10.4%), cardiovascular disease in 13 (6.1%), type 2 diabetes mellitus in 12 (5.7%), renal dysfunction in 9 (3.8%), osteopenia/osteoporosis in 8 (3.8%) patients. Although two most common regimens in the first step therapy were tenofovir disoproxil fumarate/emtricitabine + lopinavir/ritonavir, and tenofovir disoproxil fumarate/ emtricitabine + elvitegravir/cobisistate, the second step therapy was detected as an interchange in the order of these two regimens. ART switch was detected in 71 (33.8%) patients. Leading reasons of ART switch were intolerance/toxicity in 22 (30.9%) patients, and simplification of regimen in 19 (26.7%) patients. Frequency of disorders developed after ART were 5 (2.3%) diabetes mellitus, 4 (1.9%) renal diseases, 5 (2.3%) cardiovascular events, 4 (1.9%) osteopenia, and 4 (1.9%) osteoporosis. Conclusions: HIV infection is controlled with ART and life expectancy is prolonged. Patients must be evaluated carefully for metabolic risk factors in the beginning of the treatment and treatment regimen should be selected by considering these situations. The side-effects such as hyperlipidemia, diabetes mellitus, cardiovascular diseases, bone metabolic disorders, osteopenia ve osteoporosis may also develop during the treatment. Therefore, patients must be closely monitored for the possible side-effects, and physicians must work in cooperation with the related specialties, and ART switch must be performed when required. Klimik Dergisi 2020; 33(3): 241-7. [ABSTRACT FROM AUTHOR]

Objective: In order to manage the antimicrobial treatment of patients with cholangitis/cholecystitis properly, it is very important to predict the potential causative pathogens and their antimicrobial resistance patterns. The aim of this study is to provide data for empirical treatment approaches by identifying the causative agents of biliary tract infections and their antimicrobial susceptibilities, and the risk factors in patients infected with drug-resistant microorganism. Methods: Hospitalized patients with cholangitis/cholecystitis developed primarily or secondary to a biliary tract intervention, and whose bile samples for culture could be obtained, were included in the study during a 9-month period. Bile cultures were incubated in an aerobic environment, and antimicrobial susceptibilities were tested by disk diffusion method. Isolated strains that were resistant to at least two major antimicrobial groups were regarded as "drug-resistant". Risk factors for development of infection with a drug-resistant pathogen were evaluated by univariate analysis. Results: A total of 76 bacteria were isolated from 58 bile samples obtained from patients with biliary tract infections. While 30 (39.5%) bacteria were in the drug-resistant group, patients infected with these agents were found to be 26 (44.8%). All drugresistant strains of Escherichia coli were producing extendedspectrum β-lactamases, and carbapenem resistance was seen among Pseudomonas aeruginosa strains only. Antimicrobial usage during last 3 months before diagnosis (p=0.01) and duration of hospital stay before the infective episode (p=0.03) were found to be risk factors for cholangitis due to drug-resistant agents. Conclusions: In order to guide the empirical treatment of patients with cholangitis/cholecystitis properly, antimicrobial susceptibility patterns of causative agents should be monitored closely and drug-resistant pathogens should be considered in patients with a history of antimicrobial usage during the last 3 months or who have been hospitalized for a long time before the infective episode. closely and drug-resistant pathogens should be considered in patients with a history of antimicrobial usage during the last 3 months or who have been hospitalized for a long time before the infective episode. [ABSTRACT FROM AUTHOR]

Objective: Methicillin-sensitive Staphylococcus aureus (MSSA) is frequent cause of bacteraemias and associated with substantial mortality. We defined risk factors for mortality among patients with either community-acquired (CA) or healthcare-associated (HCA) MSSA bacteraemia with special emphasis on treatment options including cefazolin and other antimicrobials (mainly ampicillin- sulbactam). Material and Method: All adult patients who were hospitalized and whose blood cultures were positive for MSSA between 2009 and 2014 were included. Patients with CA and HCA MSSA bacteraemia were compared. Results: 83% of the 127 patients with MSSA bacteraemia had HCA. The mortality rate of patients was 20.5% and this did not differ between patients with either CA or HCA MSSA bacteraemia. In the multivariate analysis, higher comorbidity index (HR 1.557), presence of metastatic foci (HR 2.883), and requirement for ICU support (HR 16.239) were found as independent risk factors for mortality, and cefazolin use was found to be protective against mortality (HR 0.178). Conclusion: Patients with MSSA bacteraemia should be treated with cefazolin instead of other antimicrobial options, especially in countries where anti-staphylococcal penicillins are not available or in patients who cannot tolerate anti-staphylococcal penicillins, as cefazolin was found to be protective against mortality. [ABSTRACT FROM AUTHOR]

Objective: Recommended combination for the treatment of serious Stenotrophomonas maltophilia infections is ticarcillinclavulanate and co-trimoxazole (SXT). However, first agent is not available in our country, and the second component may be a matter of antimicrobial resistance or intolerance. Therefore, we aimed to evaluate antimicrobial susceptibility testing results of S. maltophilia and in vitro activity of ceftazidime and moxifloxacin as a potential therapeutic alternative. Methods: S. maltophilia strains isolated from clinical samples in Infectious Diseases and Clinical Microbiology Laboratory between 1 October 2007-23 November 2017 were included in the study. Disk diffusion antimicrobial susceptibility test results of the strains were evaluated retrospectively. The in vitro activity of combination of ceftazidime and moxifloxacin against 24 of these strains was investigated by Etest®. Results: During the study period, 649 S. maltophilia strains were isolated from 649 different patients, and 94%, 93%, 92%, 81%, 60%, 55%, 45%, 41%, 38% of the strains were susceptible to tigecycline, moxifloxacin, SXT, ciprofloxacin, cefoperazonesulbactam, ceftazidime, netilmicin, gentamicin and amikacin, respectively. For the 24 strains included in the combination study, the moxifloxacin minimal inhibitory concentration (MIC)50/MIC90 values were defined as 0.064/0.125 µg/mL (MIC range 0.023-4 µg/mL) and ceftazidime MIC50/MIC90 values were defined as 32/256 µg/mL (MIC range 1.5-256 µg/mL). According to the results of fractional inhibitor concentration (FIC) index; ceftazidime and moxifloxacin combination displayed synergism, additivity and indifference for 1 (4%), 18 (75%) and 5 (21%) strains, respectively and there was no antagonism. The FIC50/ FIC90 value is calculated as 0.75/1.01 (FIC range 0.5-1.01). Conclusions: SXT resistance in S. maltophilia strains is below 10%, but it should be closely monitored because of the limited treatment options. Tigecycline and moxifloxacin can be among the treatment alternatives because of their high sensitivity rates similar to SXT. The combination of moxifloxacin plus ceftazidime demonstrated in vitro synergism or additivity against majority of the strains. So, this combination may be used as an alternative for the treatment of patients with S. maltophilia infections if there is resistance or side effects to the antibiotics used as the first option. [ABSTRACT FROM AUTHOR]

Objective: We aimed to find the incidence and risk factors of hematologic adverse effects of piperacillin-tazobactam (TZP). Materials and Methods: Adult patients who used TZP for more than 10 days were included in the study. Results: The incidence of leukopenia, neutropenia, and eosinophilia in 110 TZP therapy episodes was found to be 16.3%, 10%, and 10%, respectively. Lower Charlson Comorbidity Index score, lower initial leukocyte count, combination of TZP with another antibiotic, and total duration of TZP therapy were found to be independent risk factors for leukopenia, while initial higher eosinophil count (IHEC) and usage of TZP for >20 days were independent risk factors for neutropenia and IHEC and total duration of TZP therapy were independent risk factors for eosinophilia. Conclusion: Longer duration of therapy, combination with other antibiotics, younger age with fewer comorbidities, and IHEC could result in hematologic adverse effects in patients treated with TZP. Patients with IHEC may be more prone to allergic reactions, so immunological mechanisms may facilitate the development of hematological adverse effects of TZP. [ABSTRACT FROM AUTHOR]

Objectives We described the clinical outcomes of the diabetic patients who had foot infections with multidrug resistant organisms. Methods We included the patients with diabetic foot infections (DFI) from 19 centers, between May 2011 and December 2015. Infection was defined according to IDSA DFI guidelines. Patients with severe infection, complicated moderate infection were hospitalized. The patients were followed-up for 6 months after discharge. Results In total, 791 patients with DFI were included, 531(67%) were male, median age was 62 (19–90). Severe infection was diagnosed in 85 (11%) patients. Osteomyelitis was diagnosed in 291(36.8%) patients. 536 microorganisms were isolated, the most common microorganisms were S. aureus (20%), P. aeruginosa (19%) and E. coli (12%). Methicillin resistance (MR) rate among Staphylococcus aureus isolates was 31%. Multidrug resistant bacteria were detected in 21% of P. aeruginosa isolates. ESBL (+) Gram negative bacteria (GNB) was detected in 38% of E. coli and Klebsiella isolates. Sixty three patients (8%) were re-hospitalized. Of the 791 patiens, 127 (16%) had major amputation, and 24 (3%) patients died. In multivariate analysis, significant predictors for fatality were; dialysis (OR: 8.3, CI: 1.82–38.15, p = 0.006), isolation of Klebsiella spp. (OR:7.7, CI: 1.24–47.96, p = 0.028), and chronic heart failure (OR: 3, CI: 1.01–9.04, p = 0.05). MR Staphylococcus was detected in 21% of the rehospitalized patients, as the most common microorganism (p < 0.001). Conclusion Among rehospitalized patients, methicillin resistant Staphylococcus infections was detected as the most common agent, and Klebsiella spp. infections were found to be significantly associated with fatality. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) has a high mutation rate due to its unusual replication strategy leading to the production of a large number of virions with single and double mutations. The mutations, in turn, are associated with the development of drug resistance to nucleos(t)ide analogs (NUCs) in patients before and during NUCs therapy. Objectives: The current study aimed at investigating the molecular characterization of HBV in Turkish patients with chronic hepatitis B (CHB) infection. Methods: Polymerase chain reaction (PCR) amplificationanddirect sequencing procedures were used to analyze mutations. The detected drug resistance mutations were divided into the nucleos(t)ide analogs primary, partial, and compensatory resistance groups. The amino acid substitutions of hepatitis B surface antigen (HBsAg) were categorized into antiviral drug - associated potential vaccine - escape mutations (ADAPVEMs) and typical HBsAg amino acid substitutions, which included hepatitis B hyperimmunoglobulin (HBIg) - selected escape mutation, vaccine escape mutation, hepatitis B misdiagnosis, and immune - selected amino acid substitutions. Results: The number of patients included in the study was 528 out of which 271 (51.3%) were treatment - naive and 351 (66.3%) were hepatitis B e antigen (HBeAg) - negative. Moreover, 325 (61.6%) were males with a mean age of 38 years (range: 18 - 69). Primary, partial, and compensatory resistance to NUCs was reported in 174 (32.9%) patients. Six different ADAPVEM motifs were determined in both treatment - naive and treatment - experienced patients, namely, sF161L/rtI169X, sE164D/rtV173L, sL172L/rtA181T, sL173F/rtA181V, sS195M/rtM204V, and sS196L/rtM204I. The prevalence of ADAPVEMs and typical HBsAg escape mutations was 5.3% (n = 28) and 34.8% (n = 184), respectively. Conclusions: The analysis of drug resistance should constitute a fundamental part of the follow - up period of patients with CHB undergone treatment with NUCs. The surveillance of development of drug resistance mutations, while receiving treatment for hepatitis B is of paramount importance to monitor and control the emerging resistance. [ABSTRACT FROM AUTHOR]

Objective: Plasmodium falciparum acquired abroad, has become the main causative malaria agent in Turkey due to the elimination of endemic P. vivax in recent years. By describing clinical, laboratory and treatment features of imported malaria cases caused by P. falciparum, we aimed to distinguish it from other infectious diseases with similar epidemiological and clinical features, such as viral haemorrhagic fevers, and therefore to ensure the recognition of this kind of deadly malaria earlier. Methods: All cases hospitalized in Department of Infectious Diseases and Clinical Microbiology, Istanbul Faculty of Medicine, Istanbul University with a diagnosis of malaria between 2000 and 2016 were included in the study. Epidemiological, clinical, laboratory features and antimalarial drugs used either for prophylaxis or treatment of the cases were retrieved from the hospital database retrospectively. Results: A total of 16 patients diagnosed as having malaria caused by P. falciparum were followed our clinic during the study period. Apart from one patient who had visited Afghanistan, all of the cases acquired the infection during an Africa visit. Except two patients who received irregular prophylaxis, none of the patients had used prophylactic drugs for prevention of malaria. All of the patients had fever and shaking chills. The most frequently encountered pathologic laboratory findings were thrombocytopenia and elevated serum LDH levels. Of the patients, 50% had severe malaria and 31% were followed in intensive care unit. Artemether-lumefantrine was the most frequent (44%) regimen for treatment. All patients were discharged with full recovery except one lost due to cerebral malaria. Conclusions: Patients who acquired malaria abroad are most likely to acquire a more severe form of the disease because of the lack of the antibodies resulting from previous exposure. To avoid this severe disease, it is important to give more attention to appropriate prophylaxis against malaria among persons who plan to visit endemic areas. [ABSTRACT FROM AUTHOR]