Heterologous Versus Homologous COVID-19 Boosters: Immune Response Outcomes in Renal Transplant Recipients.

We aimed to investigate the immune responses to homologous and heterologous COVID-19 booster vaccinations in renal transplant recipients (RTRs) and to identify factors affecting these responses. In this prospective multicenter observational study, we measured the antibody kinetics of 90 RTRs using the chemiluminescent microparticle immunoassay method. The mean age of participants was 45.2 ± 11.4 years, with 35.6% being female. On the 42nd day after the first vaccine dose, the median antibody level was 16.7 (IQR 2.5-249.5) AU/mL, and the seropositivity rate was 60% (n = 36). Mycophenolic acid (MFA) (OR: 0.087, 95% CI: 0.024-0.311) and ACE inhibitor use (OR: 0.203, 95% CI: 0.052-0.794) were identified as independent factors affecting seropositivity. Patients who received the Pfizer/BioNTech booster had significantly higher antibody levels compared to those who received the CoronaVac/Sinovac booster (p = 0.021). Additionally, a significantly higher rate of COVID-19 positivity was observed among patients who received the CoronaVac/Sinovac booster (p = 0.031). Heterologous COVID-19 booster vaccination is significantly more effective than homologous inactivated booster vaccination in enhancing immune responses and preventing new infections in RTRs. MFA and ACE inhibitor usage were independent factors affecting seropositivity. Additional COVID-19 vaccine doses are needed in this patient group.

Polymyxin B vs. colistin: the comparison of neurotoxic and nephrotoxic effects of the two polymyxins.

BACKGROUND: The study aimed to compare polymyxin B with colistimethate sodium (CMS) regarding neurotoxicity, nephrotoxicity and 30-day mortality in patients with MDR Gram-negatives. METHODS: All adult patients who received polymyxin B or CMS for at least 24 h for the treatment of MDR microorganisms were evaluated retrospectively. RESULTS: Among 413 initially screened patients, 147 patients who were conscious and able to express their symptoms were included in the neurotoxicity analysis. 13 of 77 patients with polymyxin B and 1 of 70 with CMS had neurotoxic adverse events, mainly paresthesias. All events were reversible after drug discontinuation. Among 290 patients included in nephrotoxicity analysis, the incidence of acute kidney injury (AKI) was 44.7% and 40.0% for polymyxin B and CMS, respectively (p = 0.425). AKI occurred two days earlier with colistin than polymyxin B without statistical significance (median (IQR): 5 (3-11) vs. 7 (3-12), respectively, p = 0.701). Polymyxin therapy was withdrawn in 41.1% of patients after AKI occurred and CMS was more frequently withdrawn than polymyxin B (p = 0.025). AKI was reversible in 91.6% of patients with CMS and 79% with polymyxin B after the drug withdrawal. Older age, higher baseline serum creatinine and the use of at least two nephrotoxic drugs were independent factors associated with AKI (OR 1.05, p < 0.001; OR 2.99, p = 0.022 and OR 2.45, p = 0.006, respectively). Septic shock, mechanical ventilation, presence of a central venous catheter and Charlson comorbidity index (OR 2.13, p = 0.004; OR 3.37, p < 0.001; OR 2.47, p = 0.004 and OR 1.21, p p < 0.001, respectively) were the independent predictors of mortality. The type of polymyxin was not related to mortality. CONCLUSIONS: Neurotoxicity is a relatively common adverse event that leads to drug withdrawal during polymyxins, particularly polymyxin B. Nephrotoxicity is very common during polymyxin therapy and the two polymyxins display similar nephrotoxic events with high reversibility rates after drug withdrawal. Close monitoring of AKI is crucial during polymyxin therapy, particularly, for elderly patients, patients who have high baseline creatinine, and using other nephrotoxic drugs.

Comparison of homologous and heterologous inactivated and mRNA vaccination programme against SARS-CoV-2 in dialysis patients.

AIM: To evaluate the vaccine response and the effect of the booster dose on COVID-19 positivity in haemodialysis (HD) and peritoneal dialysis (PD) patients who received and did not receive BNT162b2 as a booster dose after two doses of CoronaVac. METHODS: The study included 80 PD and 163 HD patients, who had been administered two doses of the CoronaVac. Antibody levels were measured on Days 42 and 90 after the first dose. Measurements were repeated on Day 181 after the first dose in the patients that received two vaccine doses and on Day 28 after the third dose in those that also received the booster dose. Antibody levels below 50 AU/mL were considered negative. RESULTS: The seropositivity rate was similar in the HD and PD group on Days 42 and 90 (p = 0.212 and 0.720). All patients were seropositive in the booster group. The antibody level was lower in the patients that received CoronaVac as the booster compared to those administered BNT162b2 in HD and PD groups (p < 0.001 and 0.002). COVID-19 positivity was detected in 11 patients (7 = had not received the booster dose, 4 = had received third dose of CoronaVac). The multivariate analysis revealed that as age increased, COVID-19 positivity also increased (OR: 1.080, 95% CI: 1.017 - 1.146, p = 0.012), while booster dose administration decreased this positivity (OR: 0.113, 95% CI: 0.028 - 0.457, p = 0.002). CONCLUSION: Our results may indicate the need for additional vaccination doses in patients with HD and PD. Our findings indicate a higher antibody response in dialysis patients with heterologous BNT162b2 as a booster dose after two doses of CoronaVac compared to homologous CoronaVac.

Successful treatment of HIV-associated progressive multifocal leukoencephalopathy (PML) with mirtazapine, mefloquine, and IVIG combination therapy: a case report.

Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the central nervous system caused by reactivation of the polyomavirus JC (JCV). Human immunodeficiency virus (HIV) infection is one of the leading causes of PML which has high morbidity and mortality due to the lack of a proven standard treatment. We found clinical and radiological improvement with the combination of high-dose methylprednisolone, mirtazapine, mefloquine, and IVIG in our patient who presented with neurological symptoms and had diagnosed concurrent acquired immunodeficiency syndrome (AIDS) and PML. To our knowledge, our case is the first HIV-associated PML which responded to this combination therapy.

In Vitro Activity of Plazomicin Against Carbapenem Resistant Klebsiella pneumoniae Strains.

BACKGROUND: In our study, we evaluated the in vitro activities of plazomicin, amikacin, gentamicin, and tobramycin among fifty carbapenem resistant Klebsiella pneumoniae (CR-Kp) isolates. Aminoglycoside resistance genes in selected CR-Kp strains were also examined. METHODS: Minimum inhibitory concentration (MIC) of meropenem, plazomicin, tobramycin, gentamicin, and amikacin were determined by gradient test (G-test) method. In all strains carbapenemase activity was assessed by polymerase chain reaction (PCR). Aminoglycoside modifying enzyme (AME) genes in 14 CR-Kp strains that are resistant to at least one of tobramycin, gentamicin, and amikacin among fifty CR-Kp isolates, and 16S ribosomal methylase genes in 6 CR-Kp strains with plazomicin MIC ≥ 128 mg/L were investigated by PCR method. RESULTS: The most frequently detected carbapenemase enzyme in the strains in our study was OXA-48 (88%). Aminoglycoside susceptibilities of all isolates were determined; plazomicin 84%, amikacin 66%, gentamicin 50%, tobramycin 18%. The most common AME gene positivities were found, 93% (n = 13) ant(3')-I, 78% (n = 11) aac(6')-Ib, 57% (n = 8) aac(3')-IV, 42% (n = 6) aac(3')-IIa, and 29% (n = 4) aph(3')-VI. Most of the isolates examined for the presence of AME carry at least two or more AME genes. The most common 16S ribosomal methylase gene was rmtH. In our study, MIC values of ≥ 256 µg/mL were found in 6 (12%) of 50 isolates against amikacin, tobramycin, and gentamicin, including plazomicin. At least two 16S ribosomal methylase gene positivity has been shown in these 6 strains. CONCLUSIONS: In our study, increased in vitro efficacy of plazomicin was shown in CR-Kp isolates comparing to other aminoglycosides. Plazomicin is an effective treatment option against CR-Kp isolates and needs to be sup-ported by clinical studies.

Prognostic Value of Serial Measurement of Serum Des-Arg(9)-Bradykinin Levels in Severe COVID-19 Patients.

BACKGROUND: Excessive inflammatory immune response during SARS-CoV-2 infection contributes to severe disease in COVID-19 patients. Recently, some researchers hypothesized that dysregulation of the bradykinin (BK) system may also play a role in the pathogenesis of severe disease. Des-Arg(9)-bradykinin (DABK), an active metabolite of BK, is responsible for vasodilatation and increased permeability in the lungs and regulated by angiotensin converting enzyme 2 (ACE-2). Viral inhibition of ACE-2 by SARS-CoV-2 increases DABK levels. Serum levels of this metabolite may be linked to disease severity in COVID-19 patients. In this study, it is aimed to investigate the prognostic value of serial measurement of serum DABK levels in severe COVID-19 patients. METHODS: This prospective cohort study was conducted in hospitalized severe COVID-19 patients. Serum DABK levels of patients were serially measured on day 0, day 3 and day 5. Patients were categorized as cases with poor or good prognosis and critical or non-critical cases. Serum DABK levels of these patient groups were compared with paired sample t-test. Serum DABK levels on different days in the same patients were compared with repeated measures ANOVA tests. RESULTS: There was no statistically significant difference in serum DABK levels measured at day 0, day 3, and day 5 between good and poor prognosis groups. DABK levels in critical and non-critical COVID-19 patients also did not show any significant difference. CONCLUSIONS: According to our results serially measured serum DABK levels did not correlate with outcome of severe COVID-19 and do not have prognostic value in severe COVID-19 patients.

Genomic characterization of SARS-CoV-2 isolates from patients in Turkey reveals the presence of novel mutations in spike and nsp12 proteins.

Novel mutations have been emerging in the genome of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2); consequently, the evolving of more virulent and treatment resistance strains have the potential to increase transmissibility and mortality rates. The characterization of full-length SARS-CoV-2 genomes is critical for understanding the origin and transmission pathways of the virus, as well as identifying mutations that affect the transmissibility and pathogenicity of the virus. We present an analysis of the mutation pattern and clade distribution of full-length SARS-CoV-2 genome sequences obtained from specimens tested at Gazi University Medical Virology Laboratory. Viral RNA was extracted from nasopharyngeal specimens. Next-generation sequencing libraries were prepared and sequenced on Illumina iSeq 100 platform. Raw sequencing data were processed to obtain full-length genome sequences and variant calling was performed to analyze amino acid changes. Clade distribution was determined to understand the phylogenetic background in relation to global data. A total of 293 distinct mutations were identified, of which 152 missense, 124 synonymous, 12 noncoding, and 5 deletions. The most frequent mutations were P323L (nsp12), D614G (ORF2/S), and 2421C>T (5'-untranslated region) found simultaneously in all sequences. Novel mutations were found in nsp12 (V111A, H133R, Y453C, M626K) and ORF2/S (R995G, V1068L). Nine different Pangolin lineages were detected. The most frequently assigned lineage was B.1.1 (17 sequences), followed by B.1 (7 sequences) and B.1.1.36 (3 sequences). Sequence information is essential for revealing genomic diversity. Mutations might have significant functional implications and analysis of these mutations provides valuable information for therapeutic and vaccine development studies. Our findings point to the introduction of the virus into Turkey through various sources and the subsequent spread of several key variants.

The prognostic role of neopterin in COVID-19 patients.

In Coronavirus disease-2019 (COVID-19) cases, hyper inflammation is associated with the severity of the disease. High levels of circulating cytokines were reported in severe COVID-19 patients. Neopterin produced by macrophages on stimulation with interferon-gamma, which is an important cytokine in the antiviral immune response, hence it can be used to predict the severity of disease in COVID-19 cases. In this study, it was aimed to determine the prognostic value of the neopterin for the prediction of severe disease in patients with COVID-19. This single-center, prospective study was conducted in hospitalized COVID-19 patients and healthy volunteers. Severe and mild COVID-19 cases were compared in terms of clinical and laboratory findings as well as serum neopterin levels on hospital admission. To assess the prognostic utility of neopterin between the severe and mild COVID-19 groups, a receiver-operating characteristic (ROC) curve was generated, and the area under the curve (AUC) was calculated. The median serum neopterin level was four times higher in COVID-19 patients than the healthy controls (46 vs. 12 nmol/L; p < .001). The AUC value of serum neopterin was 0.914 (95% confidence interval, 0.85-0.97). The sensitivity and specificity of serum neopterin for the cut-off value of 90 nmol/L to identify severe COVID-19 cases were 100% and 76%, respectively. Serum neopterin levels on hospitalization were significantly higher in severe COVID-19 disease than mild COVID-19 patients. Neopterin levels can be used as an early prognostic biomarker for COVID-19 on admission.

Prognostic value of interleukin-18 and its association with other inflammatory markers and disease severity in COVID-19.

BACKGROUND: The effectual immune response is crucial to defeat viral infections. However, exuberant immune response with features of macrophage activation syndrome (MAS) lead detrimental consequences in COVID-19 patients. Interleukin (IL)-18 is one of the leading cytokines in MAS which has not been studied in COVID-19. OBJECTIVE: To investigate the association of IL-18 with the other inflammatory markers and disease severity in COVID-19 for predicting disease prognosis. METHODS: Patients with COVID-19 who had confirmed diagnosis with SARS-CoV-2 nucleic acid RT-PCR were enrolled into the study. Data on demographic and clinical characteristics, and laboratory values of CRP, ferritin, d-dimer and procalcitonin were measured on admission. Patients were followed up prospectively with a standardized approach until hospital discharge or death. Individuals were classified as asymptomatic, mild and severe pneumonia according to their clinical, laboratory and radiological characteristics. Worse outcome was defined as requirement of intensive care unit (ICU) admission or death. Blood samples were collected at enrollment and serum levels of IL-6 and IL-18 were determined by ELISA. Association between IL-18 and other inflammatory markers and prognosis were analyzed. RESULTS: There were 58 COVID-19 patients (50% male) with a median age of 43 (min 22-max 81) years. Twenty age and sex matched healthy subjects were served as control group. The study population was divided into three groups according to disease severity: asymptomatic (n = 20), mild pneumonia group (n = 27) and a severe group (n = 11). During follow up nine (15.5%) patients required ICU admission and three of them were died eventually. Serum IL-18 were correlated with other inflammatory markers and biochemical markers of organ injury; creatinine, liver enzymes and troponin. Serum IL-18 levels were remarkably higher in COVID-19 patients compared to healthy subjects with being highest in severe pneumonia group (p < 0.001). IL-18 serum concentrations were almost four-fold higher in patients with worse outcome compared to good outcome (p < 0.001). Serum IL-18 above the cut off value of 576 pg/mL on admission was associated with 11.7 fold increased risk of ICU admission. CONCLUSIONS: The serum concentrations of IL-18 correlate with other inflammatory markers and reflect disease severity. Results of the present study shed light on role of IL-18 on COVID-19 pathogenesis and might provide an evidence for the clinical trials on IL-18 antagonists for the treatment of severe COVID-19 patients.

The assessment of serum ACE activity in COVID-19 and its association with clinical features and severity of the disease.

Angiotensin-converting enzyme (ACE)/Angiotensin (Ang) II pathway has crucial regulatory effects on circulatory hemostasis and immune responses. This pathway has a major role in the development of acute lung injury and acute respiratory distress syndrome (ARDS), which is a devastating complication of SARS-CoV-2 infection. The aim of this study is to investigate the serum ACE activity and its correlation with clinical features and the disease severity in patients with COVID-19. Patients with confirmed COVID-19 by detecting SARS-CoV-2 nucleic acid RT-PCR were included in the study. Demographic data, clinical features, laboratory and radiologic investigations were recorded. Patients were classified by disease severity; asymptomatic, mild, and severe pneumonia. The serum ACE activity was evaluated with an autoanalyzer based on a spectrophotometric method. Fifty-five patients (50.9% female) and 18 healthy subjects (33.3 % female) were enrolled in the study. The median age of patients was 40 years, ranging from 22 to 81 years. Eighteen healthy subjects were served as the control group. The baseline characteristics were comparable between groups. The median serum ACE activity of patients and controls (38.00 [IQR 21] U/L and 32.00 [IQR 24] U/L, respectively) and of between patients grouped by disease severity (38.5 [IQR 19], 36 [IQR 25], and 38 [IQR 22] U/L, asymptomatic, mild and severe pneumonia group, respectively) were similar. There was no correlation between the serum ACE activity and conventional inflammatory markers. In this study, we did not find an association between serum ACE activity and COVID-19 and serum ACE activity on admission did not reflect disease severity.

Early predictors of acute kidney injury in COVID-19 patients.

AIM: This study aims to determine the frequency of COVID-19 related AKI and to identify the early predictors of AKI. METHODS: This study is a single-center, retrospective, observational study. Hospitalized COVID-19 patients between 24/03/2020 and 31/05/2020 were included in the study. All patients were evaluated for renal dysfunctions with urine dipstick, protein/creatinine ratio, albumin/creatinine ratio in spot urine, serum cystatin C, serum creatinine level on hospital admission, and 28th day of hospital admission. To assess the utility of these parameters to predict AKI, a receiver-operating characteristic curve was generated and the area under the curve (AUC) was calculated. RESULTS: 348 patients were included. The average incidence of AKI was 4.9% (n = 17). The incidence of AKI in mild, moderate and severe COVID-19 cases was 1.3% (n = 4), 9.0% (n = 3) and 76.9% (n = 10), respectively. Proteinuria was detected in 7.8% (n = 27) of patients with a urine dipstick test. In spot urine analysis, proteinuria was found in 20.1% (n = 70) of patients. The frequency of persistent proteinuria was 5.2% (n = 18). The AUC alue of serum cystatin C, D-dimer and albumin/creatinine ratio to predict COVID-19 related AKI were 0.96 (0.90 to 1.0), 0.94 (0.89-0.98), and 0.95 (0.91-0.98). CONCLUSION: In COVID-19 patients with normal serum creatinine levels on hospital admission, albuminuria, serum cystatin C and D-dimer levels may be an early predictor of COVID-19 related AKI and these patients should be monitored closely for AKI. Since the sample size in the AKI group was small, our study results should be confirmed with larger cohort studies.

Monoclonal outbreak of Ralstonia solanacearum catheter-related bloodstream infection associated with contaminated package of normal saline solution in a tertiary care hospital

Background/aim: Ralstonia solanacearum is a very rare cause of infection in humans. There is no described nosocomial outbreak due to R. solanacearum so far. We determined R. solanacearum as the source of catheter-related bloodstream infection (CRBSI) outbreak. Materials and methods: This outbreak analysis was carried out in a 1000-bed tertiary care university hospital in Turkey. The outbreak analysis included hematology, oncology, nephrology, gastroenterology wards, emergency department, and intensive care units. The first case with R. solanacearum CRBSI was detected on May 20, 2019 and R. solanacearum was isolated in catheter blood cultures in 34 patients until October 3, 2019 Results: Standard outbreak analysis procedures were applied. Culture samples were taken from the fluids administered via catheters. The cultures did not yield any bacteria. As a result of the investigation in storage area, it was found that there were leaks, air bubbles, and water drops inside the packaging of saline solutions. R. solanacearum was yielded in the cultures obtained from the surface of saline bags and the inner sides of plastic packings. To validate our hypothesis, a clonal analysis was performed using arbitrarily primed-PCR method and Sanger sequencing of the 16S rRNA gene for identification among isolates. All R. solanacearum isolates were monoclonal and identical. Conclusion: This is the first outbreak of R. solanacearum CRBSI described in a hospital setting. The source of the outbreak was a contamination in the surface of saline bags and the inner sides of plastic packings. Efficacy of an active surveillance system, accurate and rapid conduction of microbiological identification are essential for outbreak management.

Assessment of olfactory and gustatory functions in COVID-19 patients

Background/aim: This study aims to evaluate of olfactory and gustatory functions of COVID-19 patients and possible risk factors for olfactory and gustatory dysfunctions. Materials and methods: The cross-sectional study included adult patients who were diagnosed with COVID-19 in Gazi University Hospital between April 2020 and June 2020. Volunteered patients participated in a survey in which olfactory and gustatory functions and various clinical information were questioned. Sinonasal Outcome Test-22 was also administrated to all patients. Results: A hundred and seventy-one patients participated in this study. Olfactory and gustatory dysfunctions rates were 10.5% (n: 18) and 10.5% (n: 18), respectively. Patients without any symptom other than smell and taste dysfunctions were clustered as group 1 and patients who are clinically symptomatic were clustered as group 2. Olfactory dysfunction occurred in 8% of group 1 and 17.4% of group 2 (p = 0.072). Gustatory dysfunction rate of smokers was 19.7% and significantly higher than gustatory dysfunction rate of nonsmokers (5.5%) (p = 0.007). Twenty-seven-point-eight percent of the patients with olfactory dysfunction (n = 5) were male and 72.2% (n: 13) were female. Sex did not show significant effect on rate of olfactory dysfunction. Twenty-five patients participated in psychophysical olfactory function test. No participant reported olfactory dysfunction at the time of test. Of the participants, 64% (n: 16) were normosmic and 36% (n: 9) were hyposmic according to Sniffin' Stick test. Conclusion: Olfactory and gustatory dysfunctions are more common in patients who are clinically symptomatic than those diagnosed during contact tracing. Objective tests may show that frequency of olfactory dysfunction is greater than frequency of self-reported olfactory dysfunction.

The factors predicting pneumonia in COVID-19 patients: preliminary results from a university hospital in Turkey

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.

Daptomycin vs. glycopeptides in the treatment of febrile neutropenia: results of the Izmir matched cohort study.

PURPOSE: In this multicentre, retrospective, matched cohort study we aimed to evaluate the outcomes of neutropenic fever cases that were treated with daptomycin or a glycopeptide (vancomycin or teicoplanin). METHODS: Data and outcomes of adult (aged > 18-years old) patients with neutropenic fever [(1) without clinical and radiological evidence of pneumonia, (2) who were treated with daptomycin or a glycopeptide (teicoplanin or vancomycin) for any reason and for at least 72 h] were extracted from the hospital databases. Matching was performed with all of the three following criteria: (1) underlying disease, (2) reason for starting daptomycin or glycopeptide (microbiologic evidence vs. microbiologic evidence, clinical infection vs. clinical infection and empirical therapy vs. empirical therapy) and (3) neutropenic status. RESULTS: Overall 128 patients [(69/123) (56.1%) in the daptomycin cohort (D) and 59/123 (48%) in the glycopeptide cohort (G)] had a resolution of fever at the end of 72 h antibiotic treatment (p = 0.25). There was no significant difference in cured, improved and (cured + improved) rates between (D) and (G) cohorts as well as fever of unknown origin cases or microbiologically confirmed infections or clinically defined infections subgroups (p > 0.05). There was also no significant difference (p > 0.05), in terms of persistent response in the (D) versus (G) cohorts, CONCLUSIONS: These findings suggest that although not better, daptomycin efficacy is comparable to vancomycin if used as empiric therapy in the treatment of adult febrile neutropenia. We conclude that daptomycin may be used at least as a salvage therapy alternative to glycopeptides in the treatment of adult febrile neutropenia cases. A large, randomized-controlled trial may further consolidate the evidence related to this question.

In vitro combination of tigecycline with other antibiotics in Stenotrophomonas maltophilia isolates

Background/aim: The aim of this study was to determine the usefulness of tigecycline in combination treatment of Stenotrophomonas maltophilia infections by evaluating the in vitro synergistic effects of tigecycline with various antibiotics using the E-test method. Materials and methods: Synergy testing by E-test was performed with various antibiotic combinations in 10 S. maltophilia isolates identified as a cause of infection. The antibiotics used in the study included tigecycline (TGC), cefoperazone-sulbactam (CPS), ceftazidime (TZ), levofloxacin (LEV), and trimethoprim-sulfamethoxazole (cotrimoxazole) (TS). Four different combinations (TGCCPS, TGC-TZ, TGC-LEV, TGC-TS) were studied with the E-test synergy method. Results: S. maltophilia isolates were found to have the highest level of susceptibility to trimethoprim-sulfamethoxazole, tigecycline, and levofloxacin. The fractional inhibitory concentration (FIC) index was calculated as FIC = MICAB/MICA + MICBA/MICB. The FIC index values were calculated and classified as synergistic (FIC < 0.5), additive (FIC = 0.5­1), indifferent (FIC = 1­4), and antagonistic (FIC > 4). According to FIC index values, synergy was found with the highest rate with TGC-CPS and TGC-LEV combinations (20%). Antagonistic activity was not found in any combination. Conclusion: When trimethoprim-sulfamethoxazole cannot be used because of resistance or allergy, tigecycline alone or in combination may be included as an alternative option. Although in vitro results are promising, clinical data are required.

Peripheral arterial disease increases the risk of multidrug-resistant bacteria and amputation in diabetic foot infections

Background/aim: The aim of this study was to investigate the microbiological profile and resistance rates of diabetic foot infections (DFIs) and to determine the effect of peripheral arterial disease (PAD) on the microbiology, clinical condition, and treatment outcomes. Materials and methods: Characteristics, laboratory and imaging data, and the treatment modalities of patients admitted to our hospital with a diagnosis of DFI (PEDIS classification 3­4) during 2005­2016 were analyzed according to the presence of PAD. Results: Of 112 patients who were included in this study, 86 (76.8%) had PAD. Patients with PAD were older and had higher amputation rates (P < 0.05). A microbiological profile of patients revealed a predominance of gram-positive bacteria (57.1%). Staphylococcus aureus and Streptococcus spp. were the most frequently encountered bacteria. Incidence of Pseudomonas spp. infection was higher in the PAD group (P < 0.05). Of all patients, 24.1% had multidrug-resistant (MDR) microorganisms in their wound cultures. Presence of MDR bacteria in patients with PAD was 4.9-fold higher than that in patients without PAD (P < 0.05). Conclusion: This retrospective study indicates that PAD has a significant role, especially in elderly patients with DFIs. Patients should be promptly evaluated and treated for PAD to prevent infections with resistant microorganisms and limb loss.

The in vitro effect of antimicrobial photodynamic therapy on Candida and Staphylococcus biofilms

Background/aim: This study was designed to evaluate the effect of antimicrobial photodynamic treatment (APDT) in a biofilm model using combinations of various dyes (rose bengal, riboflavin, and methylene blue) as photosensitizers and light sources (LED and UVA) against staphylococcal and candidal biofilms. Materials and methods: Sterile microtiter plates were used for the development and quantification of the biofilms. APDT was carried out using combinations of the light sources and dyes. The percentage of the growth inhibition was then calculated using a spectrophotometer. The broth media in the wells were aspirated, wells were stained with crystal violet, and optical density values were measured spectrophotometrically. SEM analysis of the impact of APDT on bacterial and fungal biofilms was also performed. Results: The experiments showed that the most efficacious combination was red LED + methylene blue against both staphylococcal and candidal biofilms. A marked inhibition (45.4%) was detected on both C. albicans and C. parapsilosis biofilms. Red LED + methylene blue was also effective on S. aureus and S. epidermidis biofilms. SEM images suggested that the number of adherent cells and biofilm mass were markedly reduced after APDT treatment. Conclusion: Although the results of this study indicated the in vitro efficacy of APDT, it might also be a promising technique for the control of biofilm growth within intravenous catheters.

Investigation of human leukocyte antigen in osteoarticular brucellosis

Background/aim: To determine the relationship between human leukocyte antigen (HLA) antigens and osteoarticular brucellosis by evaluating HLA Class I and II antigens in control subjects and patients developing osteoarticular brucellosis in Turkey.Materials and methods: The study included 28 patients with osteoarticular involvement diagnosed with brucellosis and 100 controls. The HLA Class I and II antigens were studied in isolated DNA samples using sequence-specific oligonucleotide procedure.Results: The mean age of the 28 patients and 100 controls was 42.3 ± 20.2 years and 50.1 ± 16.3 years, respectively. When the frequency of HLA Class I was examined, HLA-A*02 and HLA-B*27 antigens were detected in 50% and 28.57% of the patients, respectively. However, there was no significant difference when compared to the control group. Among the HLA Class I antigens, HLA-Cw*10 was determined in 35.71% of the patients and 17% of the controls; the difference was significant (P = 0.039).Conclusion: In the development of brucellosis, the frequency of HLA-Cw*10 among HLA Class I antigens was observed to be increased, and HLA-Cw*10 was considered likely to cause predisposition to brucellosis. Further studies to be performed on a higher number of patients and controls could demonstrate that genetic factors play a role in the diagnosis of osteoarticular brucellosis.

[Evaluation of risk factors for invasive pulmonary aspergillosis and detection of diagnostic values of galactomannan and PCR methods in bronchoalveolar lavage samples from non-neutropenic intensive care unit patients]. / Nötropenik olmayan yogun bakim hastalarinda invazif pulmoner aspergilloz için risk faktörlerinin degerlendirilmesi ve bronkoalveoler lavaj örneklerinde galaktomannan ve PCR testlerinin tanisal degerinin belirlenmesi.

Non-neutropenic intensive care unit (ICU) patients are at particular risk for invasive pulmonary aspergillosis. In these cases, radiological and microbiological methods (direct microscopy, culture), which can be used for diagnosis, have quite low sensitivity and specificity. The aims of this study were to evaluate the risk factors for invasive pulmonary aspergillosis (IPA) in non-neutropenic ICU patients and to determine the diagnostic values of galactomannan (GM) antigen and Aspergillus nucleic acid detection methods. A total of 44 patients (13 female, 31 male; age range: 36-96 years) who had been followed at pulmonary ICU with invasive mechanical ventilation and undergone bronchoscopy between January to December 2013, were included in the study. Consecutive bronchoalveolar lavage (BAL) and serum samples were obtained from all of the patients. BAL samples were tested for the presence of Aspergillus DNA by polymerase chain reaction (PCR) and both serum and BAL samples were tested for GM antigen by EIA method (Platelia Aspergillus, BioRad, France). EORTC/MSG criteria were used for the case definition of IPA. Patients were classified as high-probable IPA, possible IPA and non-IPA. ROC (receiver operating characteristics) analysis was used to determine the diagnostic values of BAL Aspergillus PCR and BAL GM in the diagnosis of IPA. Five patients were defined as high-probable IPA and six were defined as possible IPA; thus the incidence rate of IPA was estimated as 11.4% (5/44) among non-neutropenic intensive care unit patients. In high-probable IPA patients, BAL GM levels were significantly higher than non-IPA patients (p< 0.05). The prolonged duration in ICU, presence of septic shock and the use of high cumulative doses (> 460 mg) of steroid were found to be risk factors for IPA development. The cut-off value for GM in BAL samples was determined as 0.7, with a sensitivity rate of 100% (95% confidence interval: 47.9-100) and a specificity rate of 87.9% (95% confidence interval: 71.7-96.5), so optimal GM level in BAL was considered as ≥ 0.7 for the diagnosis of IPA. The specificity rates of serum GM and BAL Aspergillus PCR methods were high (97.1% and 93.9%, respectively), however their sensitivity rates were found quite low (33.3% and 40%, respectively), in the diagnosis of IPA. In conclusion, development of IPA should be assessed in non-neutropenic patients when the stay in ICU extends and high dose cumulative steroids are used. GM antigen detection in BAL can be used effectively for diagnosis of IPA in these patients compared to other diagnostic methods.