Effect of N-acetyl cysteine, rifampicin, and ozone on biofilm formation in pan-resistant Klebsiella pneumoniae: an experimental study.

BACKGROUND: To the best of our knowledge, this is the first study to evaluate the effectiveness of specific concentrations of antibiofilm agents, such as N-acetyl cysteine (NAC), rifampicin, and ozone, for the treatment of pan-resistant Klebsiella pneumoniae (PRKp). OBJECTIVES: We evaluated the effectiveness of antibiofilm agents, such as NAC, rifampicin, and ozone, on biofilm formation in PRKp at 2, 6, 24, and 72 h. DESIGN AND SETTING: This single-center experimental study was conducted on June 15, 2017, and July 15, 2018, at Istanbul Faculty of Medicine, Istanbul University, Turkey. METHODS: Biofilm formation and the efficacy of these agents on the biofilm layer were demonstrated using colony counting and laser-screened confocal microscopy. RESULTS: NAC at a final concentration of 2 µg/mL was administered to bacteria that formed biofilms (24 h), and no significant decrease was detected in the bacterial counts of all isolates (all P > 0.05). Rifampicin with a final concentration of 0.1 µg/mL was administered to bacteria that formed biofilm (24 h), and no significant decrease was detected in bacterial count (all P > 0.05). Notably, ozonated water of even 4.78 mg/L concentration for 72 h decreased the bacterial count by ≥ 2 log10. CONCLUSION: Different approaches are needed for treating PRKp isolates. We demonstrate that PRKp isolates can be successfully treated with higher concentrations of ozone.

Effect of N-acetyl cysteine, rifampicin, and ozone on biofilm formation in pan-resistant Klebsiella pneumoniae: an experimental study

ABSTRACT BACKGROUND: To the best of our knowledge, this is the first study to evaluate the effectiveness of specific concentrations of antibiofilm agents, such as N-acetyl cysteine (NAC), rifampicin, and ozone, for the treatment of pan-resistant Klebsiella pneumoniae (PRKp). OBJECTIVES: We evaluated the effectiveness of antibiofilm agents, such as NAC, rifampicin, and ozone, on biofilm formation in PRKp at 2, 6, 24, and 72 h. DESIGN AND SETTING: This single-center experimental study was conducted on June 15, 2017, and July 15, 2018, at Istanbul Faculty of Medicine, Istanbul University, Turkey. METHODS: Biofilm formation and the efficacy of these agents on the biofilm layer were demonstrated using colony counting and laser-screened confocal microscopy. RESULTS: NAC at a final concentration of 2 μg/mL was administered to bacteria that formed biofilms (24 h), and no significant decrease was detected in the bacterial counts of all isolates (all P > 0.05). Rifampicin with a final concentration of 0.1 μg/mL was administered to bacteria that formed biofilm (24 h), and no significant decrease was detected in bacterial count (all P > 0.05). Notably, ozonated water of even 4.78 mg/L concentration for 72 h decreased the bacterial count by ≥ 2 log10. CONCLUSION: Different approaches are needed for treating PRKp isolates. We demonstrate that PRKp isolates can be successfully treated with higher concentrations of ozone.

The association of CMV infection with bacterial and fungal infections in hematopoietic stem cell transplant recipients: a retrospective single-center study.

This study aims to evaluate the probable association between CMV infection and bacterial or fungalinfections in 91 consecutive adult patients who underwent autologous or allogeneic HSCT within aperiod of two years.The medical records of the patients were retrospectively reviewed. Blood cultures were evaluatedby an automated blood culture system. A quantitative real-time polymerase chain reaction was performedto detect CMV DNA.CMV infection and CMV disease were detected in 42 (46%) and six (6.6%) patients, respectively. Ofthe 158 microorganisms isolated, 115 (73%) were Gram-positive bacteria. Bacteremia and fungemiadeveloped in 55 (60%) and eight (8%) patients, respectively. Concurrent CMV infection and bacteremiawere detected in 17 (18.7%) patients and concurrent CMV infection and fungal infection weredetected in five (5.5%) patients. Graft versus host disease (GVHD) developed in 15 (50%) allogeneicHSCT recipients and two (2.2%) autologous HSCT recipients. Twenty-one (23%) patients including13 (43%) allogeneic and eight (13%) autologous HSCT recipients died.The most common infection is bacteremia, and it develops concurrently with CMV infection in approximatelyone-fifth of HSCT recipients. Gram-positive bacteria are more common in bacteremia.Further studies on the follow-up and treatment of infections after HSCT will improve post-HSCTsurvival rates.

[First Case of COVID-19 Positive Candida auris Fungemia in Turkey]. / Türkiye'de Ilk COVID-19 Pozitif Candida auris Fungemi Olgusu.

Candida auris is a species of fungus that has gained importance in recent years owing to its ability to cause hospital infections and epidemics, resistant to antifungal agents and disinfection processes and frequently misidentified by commercial systems. Hospital outbreaks caused by C.auris have been reported from some countries. It has been determined that C.auris has lower virulence than Candida albicans; however, it is associated with high mortality rates in immunocompromised individuals. An increase in the incidence of invasive fungal infections which can lead to serious complications and death, has been identified in severe coronavirus-2019 (COVID-19) patients or immunocompromised individuals with underlying disease. Studies demonstrated an increase in the frequency of C.auris isolation in COVID-19 patients with candidemia. In this report, the first case of COVID-19 positive C.auris fungemia detected in Turkey was presented. A 71-year-old male patient with a history of myocardial infarction, diabetes mellitus, donation of a single kidney and lobectomy surgery due to lung cancer was hospitalized in the pandemic thoracic surgery service due to the findings consistent with viral pneumonia on thoracic computed tomography. Favipiravir 2 x 600 mg and intravenous dexamethasone 1 x 6 mg therapy was administered. The patient tested positive for SARS-CoV-2 polymerase chain reaction, and severe involvement of the left lung was detected in the following days. Antibiotics were administered, followed by insertion of a right jugular vein catheter and initation of tocilizumab. The patient was transferred to the intensive care unit due to increased respiratory distress. Yeast growth was detected in the patient's hemoculture. The yeast strain could not be identified using API ID 32C (bioMerieux, France) (Sacchromyces kluyveri, Candida sake, unacceptable profile), but was identified as C.auris using the VITEK MALDI TOF MS (bioMerieux, France) (99.9%) system and confirmed by sequencing. The minimum inhibitor concentration values were detected as 3 µg/ml for amphotericin B; > 256 µg/ml for fluconazole; 0.19 µg/ml for voriconazole; 0.19 µg/ml for itraconazole; 0.016 µg/ml for posaconazole; 1 µg/ml for caspofungin and 0.094 µg/ml for anidulafungin by using the antibiotic gradient method. The patient's initial treatment comprised meropenem 3 x 1 g, vancomycin 2 x 1 g, caspofungin 1 x 70 mg, and continued as caspofungine 1 x 50 mg after the loading dose, and vancomycin 1 x 1 g/48 hours from the third day of treatment. The patient died on the ninth day after developing candidemia. The present case is the first case of fungemia caused by C.auris in a COVID-19 positive patient in Turkey, and it emphasizes the need of caution for fungemia due to C.auris in intensive care units in our country which has a high COVID-19 incidence.

Complementary Roles of Cadaveric and Living Donor Liver Transplantation in Acute Liver Failure.

BACKGROUND: Living donor liver transplantation may complement cadaveric transplantation in acute liver failure (ALF) patients. METHODS: Between 2008 and 2017, 89 patients were treated for ALF; 15 patients (17%) recovered with intensive care treatment; 31 (35%) died without transplant. The records of the remaining 43 patients (median (range) age: 14 (1-62)) who underwent transplantation were evaluated. RESULTS: The etiologic factors were toxic agents (10; mushrooms: 8; herbs: 2), hepatitis viruses (7; A: 1; B: 6), Wilson's disease (7), autoimmune hepatitis (4), and Budd-Chiari syndrome (2); 13 cases were idiopathic. Cadaveric organs (whole, split, reduced) were transplanted to 32 patients; 11 patients underwent living donor transplantation. One patient (2%) died of septic shock on the second postoperative day. Bacterial infection was the most common early (< 3 months) complication in the remaining patients (31/42; 74%), followed by delirium (5/42; 12%) and acute rejection requiring steroid pulse (5/42; 12%). Seven other patients died during median (range) follow-up of 94 (14-142) months: various infections (5), leukemia (1), and acute myocardial infarction (1). The 1-, 5-, and 10-year survival rates were 100%, 96%, and 92% in children and 94%, 82%, and 65% in adults respectively. CONCLUSIONS: Cadaveric organ sharing and transplantation from living donors when appropriate yield a high survival rate, despite high early morbidity, in ALF patients whose conditions deteriorate despite intensive care treatment. Efforts to eliminate preventable causes of acute liver failure will lead to more efficient use of health care resources.

Incomplete or inappropriate endoscopic and radiologic interventions as leading causes of cholangitis.

BACKGROUND: Iatrogenic factors persist as leading mechanisms of cholangitis at a referral center. METHODS: The records of 51 patients treated for cholangitis due to incomplete or inappropriate nonoperative biliary interventions between 2005-2016 were evaluated retrospectively. RESULTS: Twenty-nine patients were men; median (range) age was 60 (30-90). An incomplete or inappropriate ERCP and percutaneous transhepatic biliary drainage (PTBD) had been performed in 45 and 6 patients respectively. Inappropriate endoscopic stenting for hilar obstruction (perihilar cholangiocarcinoma: 22 and gallbladder carcinoma:3) was the most common scenario (n: 25, 49%). Twenty other patients had undergone an ERCP with incomplete (n: 12) or no (n:8) drainage. The errors in the PTBD group were passage of the catheter to the duodenum in patients with hilar obstruction (n: 4) and incomplete drainage in patients with perihilar cholangiocarcinoma (n: 2). Two patients (4%) died of infection. The surgery of 6 operable tumor patients was delayed for median (range) 5 (1-7) months. CONCLUSIONS: Incomplete or inappropriate nonoperative biliary interventions put patients' lives at risk and delay radical treatments.

Consensus Report on Diagnosis, Treatment and Prevention of Infective Endocarditis by Turkish Society of Cardiovascular Surgery (TSCVS), Turkish Society of Clinical Microbiology and Infectious Diseases (KLIMIK), Turkish Society of Cardiology (TSC), Turkish Society of Nuclear Medicine (TSNM), Turkish Society of Radiology (TSR), Turkish Dental Association (TDA) and Federation of Turkish Pathology Societies (TURKPATH) Cardiovascular System Study Group.

Infective endocarditis (IE) is rare, but associated with significant morbidity and mortality rates. Estimates of the incidence of IE in Turkey are compromised by the absence of population-based prospective studies. Due to the frequent presence of predisposing cardiac conditions and higher rates of nosocomial bacteremia in highrisk groups, the incidence of IE is expected to be higher in Turkey. Additionally, while IE generally affects older people in developed countries, it still affects young people in Turkey. In order to reduce the mortality and morbidity, it is critical to diagnose the IE to determine the causative agent and to start treatment rapidly. However, most of the patients cannot be diagnosed in their first visits, about half of them can be diagnosed after three months, and the disease often goes unnoticed. In patients diagnosed with IE, the rate of identification of causative organisms is significantly lower in Turkey than in developed countries. Furthermore, most of the centers do not perform some essential microbiological diagnostic tests as a routine practice. Some antimicrobials that are recommended as the first-line of treatment for IE, particularly antistaphylococcal penicillins, are not available in Turkey. These problems necessitate reviewing the epidemiological, laboratory, and clinical characteristics of IE in our country, as well as the current information about its diagnosis, treatment, and prevention together with local data. Physicians can follow patients with IE in many specialties. Diagnosis and treatment processes of IE should be standardized at every stage so that management of IE, a setting in which many physicians are involved, can always be in line with current recommendations. Study Group for Infective Endocarditis and Other Cardiovascular Infections of the Turkish Society of Clinical Microbiology and Infectious Diseases has called for collaboration of the relevant specialist organizations to establish a consensus report on the diagnosis, treatment, and prevention of IE in the light of current information and local data in Turkey.

Tuberculosis Mastitis: Fever of Unknown Origin in a Kidney Transplant Recipient.

Tuberculous mastitis is a rare presentation of tuberculosis, which is a major health problem in kidney transplant recipients due to its high incidence and prevalence, and difficulty in diagnosis as well as high risk of morbidity and mortality. In daily practice, physicians may frequently be led to a misdiagnosis such as breast carcinoma or abscess. We believe it is crucial for clinicians to recognize this important presentation of the disease. Therefore, we present a case of tuberculous mastitis in a kidney transplant recipient who was admitted with fever of unknown origin and successfully treated using standard anti-tuberculosis therapy without any complications.

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.

Effects of different recruitment maneuvers on bacterial translocation and ventilator- induced lung injury.

BACKGROUND: Investigated in the present study were the effects of various recruitment maneuvers (RMs) using the same inflation pressure-time product on bacterial translocation from lung to blood, and ventilator-induced lung injury (VILI). METHODS: Tracheotomy was performed on anesthetized rats, and ventilation was initiated using pressure-controlled mode. Subsequently, Pseudomonas aeruginosa was inoculated through the tracheotomy tube and ventilated for 30 minutes before rats were randomly separated into 4 groups. Group 1 underwent sustained inflation (SI), Group 2 underwent low-pressure SI, Group 3 underwent modified sigh, and Group 4 was a control group. Blood cultures were taken at baseline, 15 minutes after randomization (after each RM for the first hour), and finally at 75 minutes after the last RM. The rats were euthanized and the lungs were extirpated. The left lung was taken for measurement of wet:dry weight ratio, and the right lung was used for pathologic evaluation. RESULTS: Positive blood cultures were found to be higher in Group 3 at early study periods. Total pathological scores were also higher in Group 3. CONCLUSION: Higher severity of ventilator-induced lung injury occurred in the modified sigh group, evidenced by bacterial translocation and results of histopathological evaluation.

Recommendations for the Treatment of Invasive Fungal Infections in Hematological Malignancies: A Critical Review of Evidence and Turkish Expert Opinion (TEO-1).

The introduction of novel antifungal agents for the treatment of invasive fungal disease in hematological malignancies and also changing treatment strategies have had a great impact in managing affected patients. The medical literature includes some important clinical studies that are being used as evidence for guidelines. The problem with these studies and the guidelines is that they are not very easy to interpret, they include controversial issues, and they are not easy to apply to every patient or country. This paper was designed to critically show the main problems associated with these approaches and provide important information that will help Turkish doctors to adopt them in daily clinical practice.

Hemophagocytic Syndrome Associated with Immune Reconstitution Inflammatory Syndrome in a Patient with AIDS Related Burkitt's Leukemia/Lymphoma.

Highly active antiretroviral therapy (HAART) has markedly decreased human immunodeficiency virus- (HIV-) related mortality and the incidence of opportunistic infections. The dramatic reduction in HIV-1 RNA and increase in CD4 lymphocyte count mean a recovery in immune function. This restoration in immune function may be associated with paradoxical deterioration in subclinical opportunistic infections in some patients, a condition called immune reconstitution inflammatory syndrome (IRIS). IRIS, a "paradoxical" inflammatory response to either previously treated or subclinical infections or noninfectious diseases, can manifest during the restoration phase of immunity hemophagocytic syndrome (HS) which is a very rare complication in patients with acquired immune deficiency syndrome (AIDS). We describe a case of hemophagocytic syndrome associated with IRIS in a patient with AIDS related Burkitt's leukemia/lymphoma (BL). IRIS was probably the cause of hemophagocytosis for our patient. Zoster infection may facilitate to IRIS. With the increasing number of people with HIV infection and the accompanying use of HAART, much more clinical manifestations of IRIS will be experienced especially in patients given high dose chemotherapy, just like in our case.

A rare complication after transcanalicular dacryocystorhinostomy: tissue necrosis and nasal-cutaneous fistula.

Transcanalicular dacryocystorhinostomy (TCDCR) with diode laser is a minimally invasive technique with good cosmetic results. The reported complication rate is low. In this brief report, the authors describe a patient with tissue necrosis and nasal-cutaneous fistula after TCDCR. A 65-year-old woman attended the authors' clinic 1 month after TCDCR. Examination revealed a large tissue defect and nasal-cutaneous fistula in the medial canthal region. Aspergillus growth was noted in culture specimens taken from the nasal cavity. The patient was treated with intravenous amphotericin B. The treatment resulted in granulation and closure of the defect.

Haemophagocytosis in a patient with Crimean Congo haemorrhagic fever.

Crimean-Congo haemorrhagic fever (CCHF) is a severe disease with a case fatality of 2.8 to 80 %. A patient dwelling in an endemic region for CCHF was admitted with fever preceding bleeding diathesis and pancytopenia. Despite no history of tick exposure, CCHF was highly suspected. With an oral ribavirin therapy, clinical and laboratory improvements were obtained. The diagnosis was confirmed by detection of IgM antibody to CCHF virus and positive RT-PCR. Although the main pathogenesis of CCHF infection is not elucidated yet, haemophagocytosis, a symptom rarely reported in viral haemorrhagic fevers, was observed in this case. Haemophagocytosis is suggested to have a role in the development of pancytopenia in CCHF, the mechanism of which still needs to be investigated, probably with cytokine studies. Together with clinical symptoms and patient history, haemophagocytosis may be an indicator for CCHF.

Idiopathic necrotizing fasciitis: risk factors and strategies for management.

The prognosis of necrotizing fasciitis (NF) depends on early diagnosis and management. Idiopathic NF may be more challenging, because it occurs in the absence of a known causative factor. Therefore, our purpose in this study was to identify the distinct features of idiopathic NF that may be important in early recognition of this disease and determine the factors associated with mortality. A retrospective chart review was performed in patients with a diagnosis of NF between 1988 and 2003. Patients were classified as idiopathic and secondary NF, and data were analyzed in terms of etiological and predisposing factors, causative microbiological organisms, and clinical outcome. The study included 98 patients, 63 men and 35 women, with a diagnosis of NF. The median age was 55.5 years (range, 13 - 80). Idiopathic NF occurred in 60 of 98 patients (61%). The principal anatomic sites of infection for NF were perineal localisation in 55 patients (66%) and extremities in 31 patients (32%). Characteristics that distinguish patients with idiopathic NF from secondary NF were as follows: age older than 55 years (P = 0.0001), presence of comorbid illnesses like DM (P = 0.007) or chronic renal failure (P = 0.041), and perineal localization (P = 0.008). By logistic regression analysis, independent risk factors for idiopathic NF remained age > 55 years and perineal localization as statistically significant factors, when all the significant variables found in univariate analysis were included in the model. The majority of patients (82%) had polymicrobial infections. The mortality rate was 35 per cent. All patients were treated with radical surgical debridement and a combination of antibiotics. Female gender, presence of malignant disease, and diabetes mellitus (DM) were found to be associated with increased mortality as independent factors in logistic regression analysis, when all of these three factors were included in the model. Understanding the distinct clinical characteristics and the factors associated with mortality in patients with NF may lead to rapid diagnosis and improve the survival rates. Therefore, idiopathic NF is a crucial entity that requires serious suspicion for its diagnosis.

[The effects of immunonutrition on the development of nosocomial infections and on clinical outcome in critically ill patients]. / Yogun bakim hastalarinda uygulanan immünonütrisyonun nozokomiyal enfeksiyon gelisimine ve klinik sonuca etkisi.

BACKGROUND: We investigated the effects of early immunonutrition on the development of nosocomial infections and clinical outcome in intensive care patients. METHODS: Thirty mechanically ventilated patients were randomly assigned to two enteral nutrition regimens in the intensive care unit. Fifteen patients (8 males, 7 females; mean age 54 years; range 21 to 72 years) received immunonutrition solution containing arginine, nucleotides, and polyunsaturated fatty acids, while controls (10 males, 5 females; mean age 55 years; range 24 to 78 years) received isocaloric solution. The patients were evaluated daily using the APACHE II and SOFA (Simplified Organ Failure Assessment) scoring systems. Infections were sought in tracheal, blood, urine, and catheter cultures. Changes in nitrogen balance, leukocyte count, and APACHE II and SOFA scores were compared. RESULTS: Significant changes in nitrogen balance, APACHE II and SOFA scores, and leukocyte count were found in the study group (p<0.001, p<0.0001, p<0.0001, p<0.05, respectively), whereas no significant differences were detected in the control group. Cultures were positive in nine patients in the immunonutrition group, and in 12 patients in the control group. Septic shock and mortality rates were 26% and 20% in the study patients, and 40% and 33% in the controls, respectively (p>0.05). CONCLUSION: Patients receiving immunonutrition exhibit better nutritional status and improved scores showing clinical severity and organ failure.