Propensity Score and Desirability of Outcome Ranking Analysis of Ertapenem for Treatment of Nonsevere Bacteremic Urinary Tract Infections Due to Extended-Spectrum-Beta-Lactamase-Producing Enterobacterales in Kidney Transplant Recipients.

There are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with nonsevere bacteremic urinary tract infections (B-UTI) caused by ESBL-E. We performed a registered, retrospective, international (29 centers in 14 countries) cohort study (INCREMENT-SOT, NCT02852902). The association between targeted therapy with ertapenem versus meropenem and clinical cure at day 14 (the principal outcome) was studied by logistic regression. Propensity score matching and desirability of outcome ranking (DOOR) analyses were also performed. A total of 201 patients were included; only 1 patient (treated with meropenem) in the cohort died. Clinical cure at day 14 was reached in 45/100 (45%) and 51/101 (50.5%) of patients treated with ertapenem and meropenem, respectively (adjusted OR 1.29; 95% CI 0.51 to 3.22; P = 0.76); the propensity score-matched cohort included 55 pairs (adjusted OR for clinical cure at day 14, 1.18; 95% CI 0.43 to 3.29; P = 0.74). In this cohort, the proportion of cases treated with ertapenem with better DOOR than with meropenem was 49.7% (95% CI, 40.4 to 59.1%) when hospital stay was considered. It ranged from 59 to 67% in different scenarios of a modified (weights-based) DOOR sensitivity analysis when potential ecological advantage or cost was considered in addition to outcome. In conclusion, targeted therapy with ertapenem appears as effective as meropenem to treat nonsevere B-UTI due to ESBL-E in KT recipients and may have some advantages.

Timing of implant-removal in late acute periprosthetic joint infection: A multicenter observational study.

OBJECTIVES: We evaluated the treatment outcome in late acute (LA) periprosthetic joint infections (PJI) treated with debridement and implant retention (DAIR) versus implant removal. METHODS: In a large multicenter study, LA PJIs of the hip and knee were retrospectively evaluated. Failure was defined as: PJI related death, prosthesis removal or the need for suppressive antibiotic therapy. LA PJI was defined as acute symptoms <3 weeks in patients more than 3 months after the index surgery and with a history of normal joint function. RESULTS: 445 patients were included, comprising 340 cases treated with DAIR and 105 cases treated with implant removal (19% one-stage revision (n = 20), 74.3% two-stage revision (n = 78) and 6.7% definitive implant removal (n = 7). Overall failure in patients treated with DAIR was 45.0% (153/340) compared to 24.8% (26/105) for implant removal (p < 0.001). Difference in failure rate remained after 1:1 propensity-score matching. A preoperative CRIME80-score ≥3 (OR 2.9), PJI caused by S. aureus (OR 1.8) and implant retention (OR 3.1) were independent predictors for failure in the multivariate analysis. CONCLUSION: DAIR is a viable surgical treatment for most patients with LA PJI, but implant removal should be considered in a subset of patients, especially in those with a CRIME80-score ≥3.

Clinical outcome and risk factors for failure in late acute prosthetic joint infections treated with debridement and implant retention.

OBJECTIVES: Debridement, antibiotics and implant retention (DAIR) is the recommended treatment for all acute prosthetic joint infections (PJI), but its efficacy in patients with late acute (LA) PJI is not well described. METHODS: Patients diagnosed with LA PJI between 2005 and 2015 were retrospectively evaluated. LA PJI was defined as the development of acute symptoms (≤ 3 weeks) occurring ≥ 3 months after arthroplasty. Failure was defined as: (i) the need for implant removal, (ii) infection related death, (iii) the need for suppressive antibiotic therapy and/or (iv) relapse or reinfection during follow-up. RESULTS: 340 patients from 27 centers were included. The overall failure rate was 45.0% (153/340). Failure was dominated by Staphylococcus aureus PJI (54.7%, 76/139). Significant independent preoperative risk factors for failure according to the multivariate analysis were: fracture as indication for the prosthesis (odds ratio (OR) 5.4), rheumatoid arthritis (OR 5.1), age above 80 years (OR 2.6), male gender (OR 2.0) and C-reactive protein > 150 mg/L (OR 2.0). Exchanging the mobile components during DAIR was the strongest predictor for treatment success (OR 0.35). CONCLUSION: LA PJIs have a high failure rate. Treatment strategies should be individualized according to patients' age, comorbidity, clinical presentation and microorganism causing the infection.

Multidrug-resistant and extensively drug-resistant Gram-negative prosthetic joint infections: Role of surgery and impact of colistin administration.

Factors influencing treatment outcome of patients with Gram-negative bacterial (GNB) multidrug-resistant (MDR) and extensively drug-resistant (XDR) prosthetic joint infection (PJIs) were analysed. Data were collected (2000-2015) by 18 centres. Treatment success was analysed by surgery type for PJI, resistance (MDR/XDR) and antimicrobials (colistin/non-colistin) using logistic regression and survival analyses. A total of 131 patients (mean age 73.0 years, 35.9% male, 58.8% with co-morbidities) with MDR (n = 108) or XDR (n = 23) GNB PJI were assessed. The most common pathogens were Escherichia coli (33.6%), Pseudomonas aeruginosa (25.2%), Klebsiella pneumoniae (21.4%) and Enterobacter cloacae (17.6%). Pseudomonas aeruginosa predominated in XDR cases. Isolates were carbapenem-resistant (n = 12), fluoroquinolone-resistant (n = 63) and ESBL-producers (n = 94). Treatment outcome was worse in XDR versus MDR cases (P = 0.018). Success rates did not differ for colistin versus non-colistin in XDR cases (P = 0.657), but colistin was less successful in MDR cases (P = 0.018). Debridement, antibiotics and implant retention (DAIR) (n = 67) was associated with higher failure rates versus non-DAIR (n = 64) (OR = 3.57, 95% CI 1.68-7.58; P < 0.001). Superiority of non-DAIR was confirmed by Kaplan-Meir analysis (HR = 0.36, 95% CI 0.20-0.67) and remained unchangeable by time of infection (early/late), antimicrobial resistance (MDR/XDR) and antimicrobials (colistin/non-colistin) (Breslow-Day, P = 0.737). DAIR is associated with higher failure rates even in early MDR/XDR GNB PJIs versus implant removal. Colistin should be preserved for XDR cases as it is detrimental in MDR infections.

A long-term multicenter study: Entecavir versus Tenofovir in treatment of nucleos(t)ide analogue-naive chronic hepatitis B patients.

BACKGROUND: Entecavir (ETV) and tenofovir disoproxil fumarat (TDF) are the two first-line therapies recommended in the treatment of chronic hepatitis B because of having potent antiviral effect and high genetic barriers against resistance. We aimed to compare efficacy of these drugs and to evaluate predictors of viral suppression. METHODS: This multicenter retrospective study was conducted in nucleos(t)ide analogue-naive chronic hepatitis B (CHB) patients from different 6 centers. RESULTS: Of the 252 patients, 166 received ETV and 86 TDF. The two groups were similar in terms of age, gender, baseline ALT levels and fibrosis scores. ETV had significantly higher baseline HBV DNA, histological activity index and lower hepatitis B early antigen (HBeAg) seropositivity. Treatment duration was longer in ETV group (P<0.001). In univariate analysis, undetectable HBV DNA and ALT normalization rates were detected significantly higher in ETV groups (P<0.001 and 0.049, respectively). There was no significant difference between groups in terms of HBeAg seroconversion, virological breakthrough, time to virological breakthrough and time to ALT normalization. Entecavir was more effective in reducing HBV DNA levels at the 3rd, 6th and 12th months of the treatment (P=0.06, 0.021 and 0.012, respectively). However, multivariate Cox regression analysis indicated that TDF therapy compared to ETV had an increased probability of achieving complete viral suppression (HR=1, 66; 95% CI 1.21-2.33; P=0.010). Hepatitis B surface antigen (HBsAg) seroconversion was occurred in only one patient in ETV group. CONCLUSION: ETV leads to an early response on HBV DNA decline in the first year of the treatment. However, TDF is more successful than entecavir in achieving virological suppression.

Molecular identification of viral agents associated with acute conjunctivitis: a prospective controlled study

Abstract Background: Viral conjunctivitis are the most frequent infections in ophthalmology clinics. The diagnosis is usually relying on clinical findings and medical history. However, topical antibiotics are often used unnecessarily addition to symptomatic treatment because of unsure agents. We aimed to detect the Adenovirus, Coxsackievirus and Enterovirus from conjunctiva and pharyngeal samples of patients. Methods: The conjunctiva and pharyngeal samples of the patients with conjunctivitis were taken by Virocult transport media and kept at -80 ºC up to study day. Adenovirus spp, Enterovirus 70 and Enterovirus 71, Coxsackie A24 and Coxsackie A16 were detected by real-time PCR. Samples from healthy health care workers of ophthalmology clinic were used for control group. Results: A total of 176 samples (conjunctival and pharyngeal samples of 62 patient and 26 healthy subjects) were included. The mean age of 34 (55.7%) male and 27 (44.3%) female patients was 34 ± 17. Twenty five (40.3%) of the patients were receiving antibiotic drops at first visit. The main etiologic agent in conjunctival samples was found to be Adenovirus (46/62, 74.2%) followed by Enterovirus 70 (4/62, 6.4%) and Enterovirus 71 (4/62, 6.4%). Coxsackievirus 16 and 24 were also found in 2 patients (1/62 each, 1.6%). Pharyngeal samples were also positive for Adenovirus (20/62, 32.3%), Enterovirus 70 and 71 (7/62, 11.3% and 5/62, 8.1% respectively), Coxsackievirus 16 and 24 (2/62, 3.2% and 1/61, 1.6%). Conclusions: It is very difficult in viral conjunctivitis to make clinical differentiation caused by different agents because of common clinical signs and symptoms. In routine clinical work, the viral conjunctivitis usually related with Adenovirus. But almost one fourth of the patients' conjunctivitis were not related to Adenovirus, which shows the importance of the laboratory diagnostics. True diagnosis plays an important role on prevention of contamination and unnecessary use of antibiotics in viral conjunctivitis.

Molecular identification of viral agents associated with acute conjunctivitis: a prospective controlled study.

BACKGROUND: Viral conjunctivitis are the most frequent infections in ophthalmology clinics. The diagnosis is usually relying on clinical findings and medical history. However, topical antibiotics are often used unnecessarily addition to symptomatic treatment because of unsure agents. We aimed to detect the Adenovirus, Coxsackievirus and Enterovirus from conjunctiva and pharyngeal samples of patients. METHODS: The conjunctiva and pharyngeal samples of the patients with conjunctivitis were taken by Virocult transport media and kept at -80̊C up to study day. Adenovirus spp, Enterovirus 70 and Enterovirus 71, Coxsackie A24 and Coxsackie A16 were detected by real-time PCR. Samples from healthy health care workers of ophthalmology clinic were used for control group. RESULTS: A total of 176 samples (conjunctival and pharyngeal samples of 62 patient and 26 healthy subjects) were included. The mean age of 34 (55.7%) male and 27 (44.3%) female patients was 34±17. Twenty five (40.3%) of the patients were receiving antibiotic drops at first visit. The main etiologic agent in conjunctival samples was found to be Adenovirus (46/62, 74.2%) followed by Enterovirus 70 (4/62, 6.4%) and Enterovirus 71 (4/62, 6.4%). Coxsackievirus 16 and 24 were also found in 2 patients (1/62 each, 1.6%). Pharyngeal samples were also positive for Adenovirus (20/62, 32.3%), Enterovirus 70 and 71 (7/62, 11.3% and 5/62, 8.1% respectively), Coxsackievirus 16 and 24 (2/62, 3.2% and 1/61, 1.6%). CONCLUSIONS: It is very difficult in viral conjunctivitis to make clinical differentiation caused by different agents because of common clinical signs and symptoms. In routine clinical work, the viral conjunctivitis usually related with Adenovirus. But almost one fourth of the patients' conjunctivitis were not related to Adenovirus, which shows the importance of the laboratory diagnostics. True diagnosis plays an important role on prevention of contamination and unnecessary use of antibiotics in viral conjunctivitis.

A retrospective controlled study of thiol disulfide homeostasis as a novel marker in Crimean Congo hemorrhagic fever.

OBJECTIVES: Crimean Congo hemorrhagic fever (CCHF) is the second most common hemorrhagic fever worldwide. This study aimed to evaluate the oxidant-antioxidant balance of patients with CCHF by detecting dynamic thiol disulfide homeostasis (TDH), which is a novel oxidative stress marker, and other molecules, including paraoxonase (PON), arylesterase (ARES), ceruloplasmin (CLP), myeloperoxidase (MPO), and catalase. METHODS: This retrospective, cross-sectional, controlled study, which involved patients with CCHF and healthy volunteers, measured dynamic TDH using a novel automated method developed by Erel. RESULTS: We recruited 69 adult patients with CCHF (31 females, 38 males, median age 46 years). The case fatality rate was 1.49% (1/69). Increased disulfide/native thiol and disulfide/total thiol ratios, decreased total antioxidant status (TAS), and increased total oxidant status (TOS) were found in patients with CCHF. TAS, PON, and ARES values were found to be positively correlated with both native and total thiol levels, whereas TOS and CLP were negatively correlated with both, at a significant level. MPO activity was similar in both groups. DISCUSSION: This is the first study in the literature to evaluate dynamic TDH in CCHF. TDH shifts to the oxidative side in patients with CCHF, leading to an increase in TOS.

The Knowledge of the Physicians about Sepsis Bundles is Suboptimal: A Multicenter Survey.

OBJECTIVES: Sepsis is a severe condition with possible high mortality outcomes. A multicentre-survey to detect the knowledge of the physicians who are involved in sepsis management in daily work was conducted. MATERIALS AND METHODS: The study was held in October 2013. A questionnaire consisting of questions about sepsis bundles was prepared. Eight centers from different regions of the country were invited to join the survey. The questionnaires were introduced to physicians from infectious diseases, internal diseases, emergency (ER) and anaesthesiology departments. RESULTS: Two-hundred-and-twenty-three physicians from eight different centers were included. Of total 112 (50%) were male, median age was 30 years (24-59 years). Median working duration of participants was 5 years; 153 (69%) were residents, 70 (31%) were consultants. Of total 131 (59%) declared that they have enough knowledge on sepsis management. About the most important approach in sepsis, 151 (68%) voted for fluid replacement while 59 (26%) and 13 (6%) said early antibiotic use and inotropic support are the most important approaches respectively. Physicians from ER (56.5%) and anaesthesiology departments (55.4%) were more aware of the fluid replacement element of the bundle (30ml/kg, 3-hours bundle) in severe sepsis. The ID physicians, who routinely follow sepsis patients, were not aware of the fluid resuscitation (only 20% replied the element correctly) but almost all of them answered the question on early antibiotic use and blood culture sampling correctly. The knowledge of target CVP and MAP in severe sepsis were also below expectant among ID physicians. The overall knowledge of sepsis bundles of internal medicine physicians was poor. Almost all of the ER physicians knew that they have to measure lactate level upon admission but they were not aware of the threshold of the lactate level. CONCLUSION: The knowledge of the sepsis bundles of the physicians, who are in charge of sepsis patients in routine work, was suboptimal. Most of the participants were unaware of SSC and new bundles. Training of the physicians of all centers about sepsis bundles is suggested according to these results.

Sonographic findings in patients with Crimean-Congo hemorrhagic fever.

OBJECTIVES: Crimean-Congo hemorrhagic fever (CCHF) has been endemic in Turkey since 2002. Some radiologic findings are considered common by clinicians and radiologists. In this regard, we aimed to assess the sonographic findings in patents with CCHF in a pilot study to obtain basic knowledge for planning further controlled studies. METHODS: An observational descriptive study was planned. Patients with a CCHF diagnosis monitored by the infectious diseases department of a tertiary care hospital were included. Sonographic examinations were conducted by 2 radiologists for each patient, and the findings were recorded. RESULTS: Twenty-five patients with CCHF were included. Hepatomegaly (40%), splenomegaly (28%), paraceliac lymphadenopathy (48%), gallbladder wall thickening (36%), increased echogenicity in the renal parenchyma (40%), and fluid/effusion in the perihepatic, perisplenic, pleural, and hepatorenal recesses of the subhepatic space (Morison pouch) as well as between the intestinal loops (52%) were the primary findings. A decrease in the gallbladder wall thickening and limited resorption of intraperitoneal and pleural effusion were noted during follow-up. CONCLUSIONS: Hepatosplenomegaly, paraceliac lymphadenopathy, and gallbladder wall thickening as well as intraperitoneal and pleural effusion were the primary findings in CCHF, and they became prominent on the third day of the disease in some patients. The relationship between sonographic findings and disease severity will be investigated in an upcoming study.

Plasmodium falciparum malaria case originating from Uganda.

Malaria is the fifth infection leading to death in the world. Plasmodium species is the malarial parasite that infects human cells. The five species of the human Plasmodium parasites are P. falciparum, P. vivax, P. ovale, P. malariae and P. knowlesi. Recently, the World Health Organization reported that Uganda has the world's highest malaria incidence, with a rate of 478 cases per 1000 population per year. In this article, a patient who had specific clinical signs and symptoms of malaria after work-related travel to Uganda has been evaluated. The major clinical findings of the patient were chills and fever. After examination of thin and thick blood smears prepared from the peripheral blood of the patient, P. falciparum parasites were observed. Cerebral malaria was suspected as the patient's consciousness, orientation and cooperation had deteriorated. No Plasmodium was seen in control blood smears after treatment.

Acupuncture for depression and myalgia in patients with hepatitis: an observational study.

BACKGROUND: Depressive symptoms and myalgia are commonly seen in patients with chronic hepatitis B and chronic hepatitis C. OBJECTIVE: To investigate the efficacy of acupuncture treatment on depressive symptoms and myalgia in patients with hepatitis. METHODS: Of 44 patients with hepatitis screened for depression and myalgia, 28 were enrolled and included in the study. The main outcome measure for depressive symptoms was Beck's Depression Inventory (BDI). For pain/myalgia, patients rated their pain on a scale from 0 to 10. Patients with a score greater than the cut-off point in either score were allocated to acupuncture treatment. The Chinese method of acupuncture was used. Treatment continued for 6 weeks. RESULTS: At baseline, 17/44 patients (39%) had a BDI score ≥17 and 24 (55%) had a pain score ≥5. A total of 28 patients were allocated to acupuncture treatment, forming three groups: group 1, 13 patients with high BDI and high myalgia scores; group 2, 11 patients with low BDI score but high myalgia score; group 3, 4 patients with high BDI score but low myalgia score. Adherence to treatment was good; all patients completed the sessions and there were no drop-outs. Significant improvements in end-treatment BDI and in myalgia scores compared with baseline levels was found. CONCLUSION: Acupuncture seems to be a promising treatment for patients with hepatitis. Further studies are warranted in large populations to establish the therapeutic role of acupuncture.

[An overlooked disease of tick bites: Lyme disease]. / Kene isiriklarinda gözden kaçan bir hastalik: Lyme hastaligi.

The exact prevalence of Lyme disease caused by Borrelia burgdorferi is unknown in Turkey. However, B. burgdorferi seropositivity ranges between 6-44% among high risk groups. B. burgdorferi is transmitted to humans by the bite of infected ticks belonging to the genus Ixodes, which may be seen throughout our country. Since the Crimean-Congo Hemorrhagic Fever (CCHF) is attracting attentions to tick bites more than ever in Turkey, the patients with tick bites are followed up more cautiously and have been referred to central hospitals. In this study 4 patients who were referred to our center with prediagnosis of CCHF but later appeared to be Lyme cases, were presented. All of the cases were women, age ranging between 25-67 years old. The patients were from areas where there is high risk of CCHF. CCHF were ruled out in these patients by agent specific polymerase chain reaction and IgM results. All of the patients were clinically diagnosed as Lyme disease since they had lesions compatible with erythema migrans. B. burgdorferi total antibodies investigated by ELISA (Zeus Scientific Inc., USA) were found positive in all patients. Since Western blot method could not be performed, positive serologic results have not be confirmed. However, the diagnosis of Lyme disease was done according to Centers for Disease Control and Prevention (CDC) criteria and all of the cases have recovered following treatment with antibiotics (cefuroxime axetil or sulbactam ampicillin or amoxicillin clavulanic acid). When the increase in the incidence of arthropod-borne infections in our country is considered, it should be noted that tick-bite cases should also be evaluated in terms of Lyme disease besides CCHF. Differential diagnosis of these infections is of critical value since early appropriate therapy is important to prevent the development of serious complications in both of the disease settings.