Prevalence of Cardiovascular Disease and Comparison of Risk Category Predictions of Systemic Coronary Risk Evaluation Score-2 and 4 Other Cardiovascular Disease Risk Assessment Tools Among People Living with Human Immunodefficiency Virus in Türkiye.

BACKGROUND: Cardiovascular disease (CVD) is a major cause of mortality among people living with HIV (PLWH). We aimed to assess the prevalence of diagnosed CVD and the risk of CVD among PLWH using 5 different tools. METHODS: This retrospective, cross-sectional study was conducted in 20 tertiary centers in Türkiye between October 2021 and March 2022, among 1425 PLWH aged 40-75 years. About 82.7% were male, with a median age of 51. Web-based tools for each score were used for CVD risk calculations. RESULTS: Of 1425 PLWH enrolled, 10.8% had confirmed CVD, and 1132 had their risk scores evaluated. Of those participants, 42.8% had a higher risk of CVD (10-year risk of atherosclerotic CVD risk score (ASCVD) above 7.5%), and according to the European Society of Cardiology systemic coronary risk evaluation 2 (SCORE2), 71.7% had a high- to very high-risk rate. The agreement between various CVD risk tools varied, with Framingham heart study risk score (FRS), modified FRS, data collection on adverse effects of anti-HIV drugs (DAD), and SCORE2 for high-risk countries showing overall agreement rates of 82%, 94%, 91%, and 36%, respectively, compared to ASCVD. According to the 2021 European and 2019 American Cardiology guidelines, 75.3% and 47.1% of PLWH would be eligible for lipid-lowering agents, respectively. CONCLUSION: The diagnosed CVD prevalence highlighted the importance of monitoring cardiovascular health and comorbidities in this population. SCORE2 identified a greater number of individuals at high/very high risk compared to other prediction tools. The implementation of CVD prevention through lipid-lowering therapy was far from desired levels in our cohort.

A study on the adaptation of the HIV/AIDS-related Stigma Scale into Turkish.

PURPOSE: This study aims to test the validity and reliability of the Turkish version of the HIV/AIDS-related Stigma Scale. DESIGN AND METHODS: The study has a methodological design. The sample included a total of 428 participants. of the participants, 198 were HIV/AIDS patients, 230 were HIV-negative individuals. The data were analyzed using the Exploratory and Confirmatory Factor Analysis. FINDINGS: The Turkish version of the HIV/AIDS-related Stigma Scale was found to be valid and reliable for the Turkish society. Cronbach's α was 0.93 for the community perspectives subscale and 0.89 for the patient perspectives subscale, and all the model fit indices were acceptable. PRACTICE IMPLICATIONS: The level of stigmatization revealed by the scale helps gain an insight into the community and patient perspectives on HIV/AIDS.

Clinical, Prognostic, and Predictive Value of Olfactory Dysfunction for COVID-19: A Prospective Controlled Study.

OBJECTIVE: To evaluate the effect of olfactory dysfunction on the course and severity of COVID-19 and its prognostic and predictive significance for COVID-19. STUDY DESIGN: Prospective case-control study. SETTING: Ondokuz Mayis University School of Medicine. METHODS: Reverse transcription polymerase chain reaction (PCR)-positive patients, patients with COVID-19-related symptoms who had a negative PCR result, and healthy controls were included in the study. Clinicodemographic characteristics, inflammatory markers, and computed tomography stages were recorded. Disease progression and intensive care unit admission were registered. The visual analog scale (0, worst; 10, best) was used to evaluate subjective olfactory, taste, and nasal breathing ability, and the Sniffin' Sticks identification (SS-ID) test was used for psychophysical olfactory assessment. RESULTS: Mean SS-ID scores were significantly lower in the positive group (8.77) than in the negative (10.43) and healthy control (12.17) groups. VAS-smell scores were significantly lower and anosmia was more prevalent in PCR-positive patients (P < .01). SS-ID and VAS-smell scores were significantly correlated (r = 0.681, P < .001). The inflammatory parameters, pulmonary infiltration stage, disease progression, and ICU admission were not associated with SS-ID scores. A cutoff SS-ID score <9 resulted in 55.56% sensitivity in predicting COVID-19 positivity, and a cutoff VAS-smell score <8 yielded 72.22% sensitivity. CONCLUSION: Olfactory dysfunction was detected objectively and subjectively in the PCR-positive group, and no difference was found in terms of taste function and nasal breathing. The severity and prognosis of COVID-19 are not exclusively dependent on olfactory dysfunction. The degree of olfactory dysfunction can be useful in predicting PCR positivity.

HIV and SARS-Cov-2 Co-Infection: A Local Perspective.

Objective: As the Coronavirus disease 2019 (COVID-19) pandemic spread globally, more human immunodeficiency virus (HIV) positive patients began to appear infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to evaluate the clinical course of HIV and SARS-CoV-2 co-infected patients from a local perspective. Methods: HIV and SARS-CoV-2 co-infected patients diagnosed between March 2020 to June 2021 at a tertiary hospital in Turkey were analyzed retrospectively. Results: Thirty HIV and SARS-CoV-2 co-infected patients were included. Five patients were female, 25 were male, and the mean age was 44.5 ±10.2 years. Twenty-three (76.7%) patients were known to be HIV-positive before their admission to the hospital, and seven (23.7%) patients, were detected by screening after the diagnosis of COVID-19. All patients were known to be HIV-positive; they were on antiretroviral therapy (ART) and virologically suppressed. Twenty-seven patients had a mild course. Three patients were hospitalized, and of them, two patients had died. All hospitalized patients were male and were ART-naïve. Conclusion: HIV infection alone did not increase the severity of the course of COVID-19 and did not increase the mortality in COVID-19.

Evaluation of pain in patients with COVID-19.

OBJECTIVES: A new type of coronavirus outbreak has emerged in China and caused a pandemic. World Health Organization (WHO) announced the official name of this disease 'COVID-19'. The main purpose of this study is to evaluate pain in COVID-19 patients. METHODS: Patients who were followed in the ward of an infectious diseases department because of possible or confirmed COVID-19 between May and September of 2020 were included in the study. The Turkish version of the Brief Pain Inventory (BPI) was applied. Demographic features, frequency, location, the intensity of pain, and response to analgesics were analyzed. RESULTS: A total of 178 participants were included in the study. Ninety-one (51.1%) of patients had pain complaints and the mean pain score (MPS) was 2.28±2.81 over 10. Fifty-nine (56.0%) of participants with pain required analgesic therapy and 41 (80.3%) of them showed ≥50% pain relief with simple analgesics. Twelve of the remaining 18 who did not get enough pain relief with simple analgesic were taking their analgesics pro re nata (PRN) rather than around the clock (ATC). Pain frequency and intensity and mean hospitalization duration (MHD) were similar between confirmed and possible cases. CONCLUSION: Regarding the results, we conclude that pain is not one of the challenging symptoms and easily manageable in patients with a mild-moderate intensity of COVID-19. Our results were not enough to make a correlation between pain and the clinical course of the disease. Further studies are required for the evaluation of pain including patients in intensive care units.

Relationship between acute phase reactants and prognosis in patients with or without COVID-19 pneumonia.

In December 2019, several cases of pneumonia of unknown origin were reported in the city of Wuhan, province of Hubei, China. The pathogen was named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the disease was named coronavirus disease 2019 (COVID-19). Acute phase reactans (APRs) are critical in the early diagnosis, treatment, and for monitoring the progression of COVID-19. Seventy two patients were included in the study and infections confirmed by real-time reverse transcription polymerase chain reaction. Clinical parameters, the level of APFs and D-dimer were assessed and results were retrived from the patients' medical records. Chest computed tomography (CT) findings were described for each patient and they were divided into two groups, with or without COVID-19 pneumonia. The correlation between APRs and CT findings and the patients' prognosis were evaluated. Twenty eight (38.8%) of the 72 patients were female and 44 (61.2%) were male. The most common symptom was cough (43%) and the most common associated chronic disease was hypertension (12.5%). Thirty (41.6%) patients had completely normal chest CT, while 42 (58.4%) patients had typical findings in terms of COVID-19 pneumonia. C reactive protein (CRP), lactate dehydrogenase (LDH), erythrocyte sedimentation rate (ESR), ferritin, procalcitonin and D-Dimer levels were statistically significantly higher in patients with pneumonia than in those without pneumonia and these parameters were also statistically significantly higher in patients with severe illness. In conclusion, CRP, LDH, ESR, ferritin, and D-Dimer were associated with severe COVID-19 pneumonia. These biomarkers can be used to evaluate the prognosis to predict the clinical course of disease, allowing a proper management and treatment of the patients.

Evaluation of neutrophil to lymphocyte ratio in predicting the prognosis of Crimean-Congo haemorrhagic fever.

Crimean-Congo haemorrhagic fever (CCHF) is a severe form of haemorrhagic fever identified in parts of Africa, Asia, Eastern Europe and the Middle East. CCHF continues to be a justifiable cause of concern for people in rural areas where the disease is endemic. A total of 151 patients, diagnosed with CCHF, were evaluated retrospectively. The demographic characteristics of these patients and the relationship between the neutrophil-lymphocyte ratio (NLR) at admission and survival were examined. There were 21 (13.9%) deaths. There was no relationship between age, gender and mortality, but elevated neutrophil-lymphocyte ratio (NLR) on admission was statistically associated with mortality. NLR is a laboratory marker that can be studied even in medical centres with limited facilities and may be helpful in predicting the clinical course of the disease.

Clinical significance of smell and taste dysfunction and other related factors in COVID-19.

PURPOSE: The objective of this study is to evaluate smell and taste dysfunction (STD) in coronavirus disease 2019 (COVID-19) positive and negative patients, and to assess the factors associated with STD in COVID-19 positive patients. METHODS: Patients who had been tested with the real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for COVID-19 were identified, and according to the RT-PCR test results, patients were separated into Positive and Negative Groups. A telephone-based assessment was applied to both groups using the American Academy of Otolaryngology-Head and Neck Surgery Anosmia Reporting Tool. Patients in Positive Group were also asked to rate STD, nasal breathing, and anxiety in three different time periods (pre-/during-/post-COVID) using the visual analog scale (VAS). RESULTS: A total of 53 COVID-19 positive and 51 negative patients completed the surveys. STD was eightfold more frequent (OR 8.19; CI 95% 3.22-20.84) in the Positive Group. Of the 53 COVID-19 positive patients, 32 reported STD and 21 did not. 'Ground-glass appearance' on chest-computed tomography was more frequent and median lymphocyte count was significantly lower in COVID-19 positive patients with STD. During-COVID STD and nasal breathing VAS scores were significantly lower than the pre- and post-COVID scores. During-COVID STD scores were significantly correlated with anxiety scores (Spearman's rho-0.404, p = 0.022) but not correlated with nasal breathing scores. CONCLUSION: STD may be related to increased inflammatory response as well as damage of olfactory neuronal pathway or non-neuronal olfactory mucosa. Understanding the exact cause of chemosensory impairment in COVID-19 can be helpful in explaining the pathophysiology of the disease.

Enterococcus hirae as a cause of bacteremic urinary tract infection: first case report from Turkey.

INTRODUCTION: Enterococcus hirae (E. hirae) constitutes less than 1% of the enterococci strains in human clinical specimens. In this article, we report the first case of urinary tract infection-related bacteremia due to E. hirae from Turkey. CASE PRESENTATION: A 74-year-old male patient with a history of coronary artery disease, hypertension, and chronic renal failure was admitted to the emergency department with abdominal pain, dysuria, and fever. The urine sample collected from the urinary catheter resulted as ampicillin-sensitive E. hirae. On the 4th day of hospitalization, E. hirae growth with the same sensitivity pattern was also reported in blood culture. Intravenous ampicillin 4×2 g/day treatment was initiated. There was no growth in subsequent blood and urine cultures. Fever resolved and general condition improved. The patient was discharged on the thirteenth day with clinical improvement after moxifloxacin treatment for four days and ampicillin treatment for nine days. DISCUSSION: The patient's medical history included risk factors for enterococcal bacteremia. There are a limited number of reports in the literature describing human infections caused by E. hirae. The reason for the rare isolation of E. hirae from clinical specimens may be the difficulty of identifying with standard diagnostic approaches. CONCLUSIONS: For diagnostic purposes, as in our case, rapid and high sensitive diagnostic methods such as Matrix-assisted Laser Desorption/Ionization Time of Flight (MALDI-TOF) and molecular techniques may be useful to guide the selection of the least toxic and optimal duration of antibiotic treatment.

Toxocariasis Presenting with Hypereosinophilia and Lymphadenopathy: A Case Report.

Human toxocariasis is a parasitic disease transmitted to humans by ingestion of Toxocara spp. larvae. Rural area residents and children have higher risk for this parasitic infection. The disease is frequently asymptomatic; however, it may cause symptoms such as cough, fever, headache, myalgia or other conditions such as lymphadenopathy and granulomatous hepatitis. Albendazole is used for the treatment of toxocariasis diagnosed by serologic and immunological methods. Herein, we report two cases of toxocariasis that were investigated due to hypereosinophilia and lymphadenopathy for a long time.

NS5A resistance - associated substitutions in chronic hepatitis C patients with direct acting antiviral treatment failure in Turkey.

OBJECTIVES: Chronic hepatitis C (CHC) is now a more curable disease with new direct acting antivirals (DAA). Although high sustained virologic response rates, failures still occur in DAA regimens. Our objective in this study was to characterize the real-life presence of clinically relevant resistance - associated substitutions (RASs) in the HCV NS5A gene in CHC patients whose DAA regimen has failed. METHODS: The study enrolled 53 CHC patients who experienced failure with DAA regimen as the prospective longitudinal cohort between 2017-2019. Genotypic resistance testing was performed via the viral population sequencing method and The Geno2pheno HCV tool was used for RAS analysis. RESULTS: The most frequent failure category was relapse (88%) followed by non-responder (12%). For a total of 36% of patients, RASs was detected in NS5A, Y93H was the most detected RAS in GT1b infected patients (89%). CONCLUSIONS: This study establishes an HCV failure registry for Turkey in which samples were combined with clinical, virologic and molecular data of adult patients whose DAA therapy failed. RASs can occur in CHC patients with DAA treatment failures. Evaluation of RAS after DAA failure is very important before re-treatment is initiated to prevent virologic failure.

Molecular Identification of HIV-1 in the Presence of Hepatitis B Virus and Hepatitis C Virus Co-infections

Background: Because of their similar modes of transmission, the simultaneous infection of viral hepatitis and human immunodeficiency virus are increasingly seen as a big problem related to human health. Aims: To determine the drug mutations in hepatitis B virus and/or hepatitis C virus co-infected human immunodeficiency virus-1 patients in Turkey. Study Design: Retrospective cross-sectional study. Methods: The present study was conducted between 2010 and 2017. HBsAg, anti-hepatitis C virus, and anti-human immunodeficiency virus were tested with ELISA. All anti-human immunodeficiency virus positive results by ELISA were verified for anti-human immunodeficiency virus positivity by a Western blot test, and Anti-human immunodeficiency virus positive patients with HBsAg and/or anti-hepatitis C virus positivity were included in the study. Subtyping and genotypic resistance analyses were performed by population sequencing of the viral protease and reverse transcriptase regions of the human immunodeficiency virus-1 pol gene. Results: We detected 3896 human immunodeficiency virus-1 positive patients whose sera were sent from numerous hospitals across the country to our polymerase chain reaction unit for detection of drug resistance mutations and whose molecular laboratory tests were completed. Viral hepatitis co-infections were detected in 4.3% (n=170) of patients. Hepatitis B virus and hepatitis C virus co-infection were observed in 3.2% and 0.5% of all human immunodeficiency virus-1 infected patients, respectively. The major human immunodeficiency virus-1 subtype detected was group M, subtype B (62.9%). However, 13.5% of drug resistance mutation motifs were found in human immunodeficiency virus-1 genomes of patients included in the study. Conclusion: Due to similar transmission routes, HIV1 patients are at risk of hepatitis B and C virus co-infection. However, antiretroviral drug resistance mutation model is similar to patients with hepatitis negative.

Current status of HIV/AIDS-syphilis co-infections: a retrospective multicentre study.

OBJECTIVE: Treponema pallidum and HIV are transmitted frequently through sexual contact, these agents with epidemiological similarities co-infect the same host. The current number of HIV-infected cases in Turkey is increasing. For this reason, we aimed to reveal the characteristics of syphilis in HIV/AIDS cases. METHODS: A retrospective longitudinal cohort study was performed, patients were followed up at 24 clinics in 16 cities from all seven regions of Turkey between January 2010 to April 2018. We examined the socio-demographic characteristics, laboratory parameters and neurosyphilis association in HIV/AIDS-syphilis co-infected cases. RESULTS: Among 3,641 patients with HIV-1 infection, 291 (8%) patients were diagnosed with syphilis co-infection. Most patients were older than 25 years (92%), 96% were males, 74% were working, 23% unemployed, and 3% were students. The three highest prevalence of syphilis were in Black Sea (10.3%), Mediterranean (8.4%) and Marmara Regions (7.4%). As for sexual orientation, 46% were heterosexuals, 42% men who have sex with men (MSM), and no data available for 12%. Patients with the number of CD4+ ≤ 350 mm3 reached 46%, 17% of the patients received antiretroviral therapy and neurosyphilis association reached 9%. CONCLUSION: Although HIV/AIDS-syphilis co-infection status appeared high in heterosexuals, MSM had a moderate level increase in cases. Our results suggested syphilis co-infection in HIV/AIDS cases should be integral part of monitoring in a national sexual transmitted diseases surveillance system. However, our data may provide base for HIV/syphilis prevention and treatment efforts in the future.

Echocardiographic assessment of pulmonary arterial stiffness in human immunodeficiency virus-infected patients.

BACKGROUND: Pulmonary hypertension (PH) is one of the complications of human immunodeficiency virus (HIV) infection. Despite the emergence of effective therapies, pulmonary arterial hypertension is commonly seen, especially at advanced stages. At the time of diagnosis, a majority of patients are at New York Heart Association-Functional Class III or IV. Many of the current screening modalities are dependent on detecting a rise in pulmonary arterial pressure (PAP). However, high capacitance of the pulmonary circulation implies that early microcirculation loss is not accompanied by a change in resting PAP. Therefore, we aimed to demonstrate early changes in pulmonary vascular disease in HIV-infected patients with a new echocardiographic parameter, called as pulmonary arterial stiffness (PAS). METHODS AND RESULTS: Thirty-six HIV-infected patients and 36 age- and sex-matched healthy control subjects were enrolled in this study. PAS was calculated echocardiographically by using maximal frequency shift and acceleration time of the pulmonary artery flow trace. There was no significant difference in diastolic functions, right ventricular diameters, systolic PAP, inferior vena cava widths, right atrial area, and tricuspid annular plane systolic excursion values between the two groups. However, PAS was calculated as 24.3 ± 6.4 Hz/msn in HIV-infected patients and 19.3 ± 3.1 Hz/msn in healthy control group (P < 0.001). Increase in PAS was correlated with duration of HIV infection (P < 0.05). CONCLUSION: Our results suggest that HIV infection affects pulmonary vascular bed starting early onset of disease and this can be demonstrated by an easy-to-measure echocardiographic parameter.

[Prevalence of human leukocyte antigen (HLA)-B*57:01 in HIV-infected patients]. / HIV ile enfekte hastalarda insan lökosit antijeni (HLA)-B*57:01 prevalansi.

Deaths related with human immunodeficiency virus (HIV) infections have been decreased by the introduction of combined anti-retroviral therapy (ART) into the clinical practice. Combined ART usually consists of two nucleoside/nucleotide analogs reverse transcriptase inhibitors (NRTI) that is called backbone and a third drug that belongs to either non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI), integrase strand transfer inhibitors (INSTI) or entry inhibitors. During abacavir therapy which is a member of NRTI, hypersensitivity reactions can occur approximately 4-9% of the patients that lead difficulties for the management of HIV infections. It is known that, the development of hypersensitivity reactions to abacavir is strongly associated with the presence of HLA-B*57:01 allel, therefore, HLA-B*57:01 screening should be performed prior to abacavir use. Since there is no data on HLA-B*57:01 prevalence in HIV-1-infected cases in Turkey, this is the first study that screened HLA-B*57:01 allels among HIV-1 infected adults in Turkey. A total of 100 HIV-1-infected patients (81 male, 19 female; mean age: 42.31±11.97 years) who have admitted to the Department of Infectious Diseases and Clinical Microbiology of Ondokuz Mayis University School of Medicine, Samsun, Turkey, were included in the study. Genomic DNAs were isolated from the blood samples of patients by using a commercial spin column procedure (QIAamp® DNA Blood Mini Kit; QIAGEN GmbH, Germany). HLA-B*57:01 genotyping was performed by the method of sequence-specific primer (SSP)-based amplification using a commercial OlerupSSP® HLA-B*57:01 high-resolution test kit (Olerup SSP AB, Sweden) according to the manufacturer's protocol. The products of polymerase chain reaction were electrophoresed on a 2% agarose gel stained with Olerup SSP GelRed dye (Olerup SSP AB, Sweden), and the bands were evaluated under UV light. In our study, three (2 male, 1 female) out of 100 patients were found positive for HLA-B*57:01 gene with a prevalence of 3%, which is a moderate level. Although the medical usefulness of HLA-B*57:01 screening before the abacavir therapy is emphasized, it was also noted that this application is not cost-effective for the populations with low HLA-B*57:01 prevalence, in contrast to populations with high prevalence. Considering of the incidence of HIV/AIDS in Turkey which is 0.12, the value and cost-effectiveness of HLA-B*57:01 screening in HIV-1 positive cases before abacavir therapy should be analysed by further studies.

[Detection of the first QnrS gene positivity in aquatic Aeromonas spp. isolates in Turkey]. / Türkiye'de su kaynakli Aeromonas spp. izolatlarinda saptanan ilk QnrS gen pozitifligi.

Aeromonas spp. are oxidase positive, gram-negative, facultative anaerobic bacilli that are widely distributed in aquatic environments. A.hydrophila, A.sobria and A.bestiarum may cause severe infections in both human and cold-blooded animals. Environmental persistance of quinolones that are widely used in both human and veterinary medicine plays an important role in the selection of resistant mutants. Plasmid-mediated resistance is one of the main mechanisms involved in quinolone resistance, and qnr, qepA, aac(6')-Ib-cr, oqxAB genes are identified as resistance determinants. Determination of various types of qnr gene in different bacteria mainly in Enterobacteriaceae, suggests that they are widely distributed in nature. Recently, plasmid-mediated quinolone resistance was defined among Aeromonas species isolated from water. The aim of this study was to investigate the presence of qnr genes among aquatic Aeromonas spp. in Turkey. A total of 45 Aeromonas strains isolated from water and fishes collected from three different geographical regions (Aegean, Mediterranean and Blacksea) in Turkey, were included in the study. The isolates were identified at species level by the use of 16S rDNA-RFLP (Restriction fragment length polymorphism) analysis and multiplex polymerase chain reaction (M-PCR). Among the isolates, 20 were identified as A.sobria, 10 as A.hydrophila, nine as A.salmonicida, four as A.bestiarum and two as A.veronii. The plasmid-mediated quinolone resistance determinants, qnrA, qnrB, qnrC and qnrS genes, were investigated by M-PCR, and sequence analysis was performed for nine qnr-positive isolates. According to the sequence analysis of the genes, qnr genes were characterized in six A.sobria, in two A.bestiarum and in one A.hydrophila isolate (9/45; 20%). When the sequence was compared with GenBank database, this gene was found as qnrS2. All qnrS-positive Aeromonas spp. isolates were ciprofloxacin-susceptible, while five of them were resistant to nalidixic acid. This study is the first research about the plasmid-mediated quinolone resistance and the presence of qnrS2 genes among Aeromonas spp. isolated from fishes and water in Turkey. In conclusion, various resistance genes of aquatic bacteria may constitute a potential risk for the transmission of those genes to other bacteria as well as clinical isolates.

Optimum management of Citrobacter koseri infection.

Low virulent Citrobacter koseri can cause life threatening infections. Neonates and other immunocompromised patients are particularly susceptible to infection from C. koseri. Any infection due to C. koseri mandates antimicrobial therapy based on the sensitivity of the pathogen microorganism. Various types of antibiotics, including aminoglycosides carbapenems, cephalosporins, chloramphenicol and quinolones, are used for the treatment of C. koseri infections. The rational choice of antimicrobial therapy for Citrobacter infections is a challenge for clinicians because there is a sustained increase in antibacterial resistance. We reviewed antimicrobial agents used for C. koseri infections in this review.

Nitrate reductase assay for rapid detection of isoniazid, rifampin, ethambutol, and streptomycin resistance in Mycobacterium tuberculosis: a systematic review and meta-analysis.

Colorimetric phenotypic tests recently gained interest because traditional primary drug susceptibility testing of Mycobacterium tuberculosis isolates takes a long time. We used meta-analysis techniques to review the reliability and accuracy of the nitrate reductase assay (NRA), which is one of the most popular colorimetric methods to detect resistance to first-line drugs. Medline, PubMed, ISI Web, Web of Science, and Google Scholar were used to search for studies enrolled in the meta-analysis. The analysis included 35 studies for isoniazid (INH), 38 for rifampin (RIF), and 22 for ethambutol (EMB) and streptomycin (STR). Summary receiver operating characteristic (SROC) curves were applied to summarize diagnostic accuracy. The meta-analyses were performed by the use of Meta-DiSc software (version 1.4) and were focused on sensitivity and specificity values for measurements of accuracy. The pooled sensitivities were 96% for INH, 97% for RIF, 90% for EMB, and 82% for STR. The pooled specificities for INH, RIF, EMB, and STR were 99%, 100%, 98%, and 96%, respectively. The times required to obtain results were between 5 and 28 days by the direct NRA and between 5 and 14 days by the indirect test. In conclusion, the present meta-analysis showed that the NRA is a reliable low-cost rapid colorimetric susceptibility test that can be used for the detection of multidrug-resistant (MDR) tuberculosis, including detection of EMB resistance. However, the test appears to have a relatively low sensitivity for STR and needs further improvement.

Resazurin microtiter assay for isoniazid, rifampicin, ethambutol and streptomycin resistance detection in Mycobacterium tuberculosis: Updated meta-analysis.

AIMS: The present meta-analysis aims to assess the evidence regarding the diagnostic accuracy and performance characteristics of the colorimetric redox indicator (CRI) assay with a special emphasis on the use of the resazurin microtiter assay (REMA) for determination of primary anti-tuberculosis drug resistance. SUBJECT AND METHODS: By updating previous literature searches in Medline PubMed, ISI Web, Web of Science and Google academic databases of the REMA test for determination of primary anti-tuberculosis drug resistance, this meta-analysis includes 14 studies for isoniazid (INH); 15 studies for rifampicin (RIF); 6 studies for streptomycin (STR); and 5 studies for ethambutol (EMB). SROC curve analysis was performed for meta-analysis and diagnostic accuracy was summarized. RESULTS: Pooled sensitivity was 96% (94-98%) for INH, 97% (95-98%) for RIF, 92% (87-96%) for EMB and 92% (88-95%) for STR. Pooled specificity for INH, RIF, EMB and STR was 96% (95-98%), 99% (98-99%), 86% (81-89%) and 90% (87-93%), respectively. Susceptibility testing results had been obtained in 8-9days. CONCLUSION: In conclusion, REMA seems to be a reliable test for the determination of multi-drug resistant (MDR) isolates in laboratories with limited resources. However, few studies for STR and EMB have been found, and cost-effectiveness studies need to be determined to recommend its widespread use.

[In Vitro Effect of Ankaferd Blood Stopper®, a Plant Extract Against Mycobacterium tuberculosis Isolates]. / Bir Bitki Ekstresi Olan Ankaferd Blood Stopper®'in Mycobacterium tuberculosis Izolatlarina Karsi In Vitro Etkinligi.

Treatment of drug-resistant Mycobacterium tuberculosis infections requires combination of anti-tuberculosis drugs which have several toxic side effects. Thus there is a need for safer and effective new drugs. Ankaferd Blood Stopper® (ABS), which is a mixture of plant extracts prepared from Alpinia officinarum, Glycyrrhiza glabra, Thymus vulgaris, Urtica dioica and Vitis vinifera, has homeostatic and antibacterial effects. Standard solutions of ABS are already being used topically for post-traumatic and post-operative bleeding control in our country. This study was aimed to evaluate the in vitro activity of ABS against M.tuberculosis isolates. A total of 57 clinical isolates [17 multidrug resistant (MDR), 11 resistant to only isoniazid (INH), one resistant to INH and streptomycin (STR), two resistant only to STR, two resistant only to ETM, and 24 susceptible to all drugs] and three standard strains [H37Rv (susceptible to all drugs), ATCC 35822 (INH-resistant), ATCC 35820 (STR-resistant)] were included in the study. Agar dilution method was used to detect the MIC values of ABS. In the study, ABS MIC value was determined as 10.94 µg/ml for M.tuberculosis H37Rv strain which was susceptible to all anti-tuberculosis drugs, whereas it was determined as 21.88 µg/ml for INH-resistant ATCC 35822 and STR-resistant ATCC 35820 strains. The MIC values for 24 susceptible clinical isolates were as follows; 10.94 µg/ml (n= 17), 21.88 µg/ml (n= 6) and < 1.37 µg/ml (n= 1). When evaluating 17 MDR clinical isolates, MIC values were determined as 5.47 µg/ml (n= 1), 10.94 µg/ml (n= 5) and 21.88 µg/ml (n= 11). MIC values were ranging between < 1.37-21.88 µg/ml among 11 INH-resistant isolates. These isolates were susceptible to other first line anti-tuberculosis drugs. MIC value of one isolate resistant to both of INH and STR was determined as 21.88 µg/ml. MIC value of the two sole STR-resistant isolates was 21.88 µg/ml. MIC values of the two sole ETM-resistant isolates were determined as 21.88 µg/ml and 10.94 µg/ml. MIC50 and MIC90 values for the tested bacteria were 10.94 µg/ml and 21.88 µg/ml, respectively. It was concluded that 16 fold diluted concentration of the topically used ABS solution was found to be active against tuberculosis bacilli in vitro. Thus ABS might be used as a supportive agent together with anti-tuberculous drugs during debridement of multiple drug-resistant M.tuberculosis caused osteomyelitis and lymphadenitis lesions.