Clinical Predictive Model of Multidrug Resistance in Neutropenic Cancer Patients with Bloodstream Infection Due to Pseudomonas aeruginosa.

We aimed to assess the rate and predictive factors of bloodstream infection (BSI) due to multidrug-resistant (MDR) Pseudomonas aeruginosa in neutropenic cancer patients. We performed a multicenter, retrospective cohort study including oncohematological neutropenic patients with BSI due to P. aeruginosa conducted across 34 centers in 12 countries from January 2006 to May 2018. A mixed logistic regression model was used to estimate a model to predict the multidrug resistance of the causative pathogens. Of a total of 1,217 episodes of BSI due to P. aeruginosa, 309 episodes (25.4%) were caused by MDR strains. The rate of multidrug resistance increased significantly over the study period (P = 0.033). Predictors of MDR P. aeruginosa BSI were prior therapy with piperacillin-tazobactam (odds ratio [OR], 3.48; 95% confidence interval [CI], 2.29 to 5.30), prior antipseudomonal carbapenem use (OR, 2.53; 95% CI, 1.65 to 3.87), fluoroquinolone prophylaxis (OR, 2.99; 95% CI, 1.92 to 4.64), underlying hematological disease (OR, 2.09; 95% CI, 1.26 to 3.44), and the presence of a urinary catheter (OR, 2.54; 95% CI, 1.65 to 3.91), whereas older age (OR, 0.98; 95% CI, 0.97 to 0.99) was found to be protective. Our prediction model achieves good discrimination and calibration, thereby identifying neutropenic patients at higher risk of BSI due to MDR P. aeruginosa The application of this model using a web-based calculator may be a simple strategy to identify high-risk patients who may benefit from the early administration of broad-spectrum antibiotic coverage against MDR strains according to the local susceptibility patterns, thus avoiding the use of broad-spectrum antibiotics in patients at a low risk of resistance development.

Prediction of unfavorable outcomes in cryptococcal meningitis: results of the multicenter Infectious Diseases International Research Initiative (ID-IRI) cryptococcal meningitis study.

Cryptococcal meningitis (CM) is mostly seen in immunocompromised patients, particularly human immunodeficiency virus (HIV)-positive patients, but CM may also occur in apparently immunocompetent individuals. Outcome analyses have been performed in such patients but, due to the high prevalence of HIV infection worldwide, CM patients today may be admitted to hospitals with unknown HIV status, particularly in underdeveloped countries. The objective of this multicenter study was to analyze all types of CM cases in an aggregate cohort to disclose unfavorable outcomes. We retrospectively reviewed the hospitalized CM patients from 2000 to 2015 in 26 medical centers from 11 countries. Demographics, clinical, microbiological, radiological, therapeutic data, and outcomes were included. Death, neurological sequelae, or relapse were unfavorable outcomes. Seventy (43.8%) out of 160 study cases were identified as unfavorable and 104 (65%) were HIV infected. On multivariate analysis, the higher Glasgow Coma Scale (GCS) scores (p = 0.021), cerebrospinal fluid (CSF) leukocyte counts > 20 (p = 0.038), and higher CSF glucose levels (p = 0.048) were associated with favorable outcomes. On the other hand, malignancy (p = 0.026) was associated with poor outcomes. Although all CM patients require prompt and rational fungal management, those with significant risks for poor outcomes need to be closely monitored.

Correction to: Prediction of unfavorable outcomes in cryptococcal meningitis: results of the multicenter infectious Diseases International Research Initiative (ID-IRI) cryptococcal meningitis study.

In the original version of this article, Mustafa Sunbul was not included in the list of authors for this article. The name has been added accordingly.

The burden and epidemiology of community-acquired central nervous system infections: a multinational study.

Risk assessment of central nervous system (CNS) infection patients is of key importance in predicting likely pathogens. However, data are lacking on the epidemiology globally. We performed a multicenter study to understand the burden of community-acquired CNS (CA-CNS) infections between 2012 and 2014. A total of 2583 patients with CA-CNS infections were included from 37 referral centers in 20 countries. Of these, 477 (18.5%) patients survived with sequelae and 227 (8.8%) died, and 1879 (72.7%) patients were discharged with complete cure. The most frequent infecting pathogens in this study were Streptococcus pneumoniae (n = 206, 8%) and Mycobacterium tuberculosis (n = 152, 5.9%). Varicella zoster virus and Listeria were other common pathogens in the elderly. Although staphylococci and Listeria resulted in frequent infections in immunocompromised patients, cryptococci were leading pathogens in human immunodeficiency virus (HIV)-positive individuals. Among the patients with any proven etiology, 96 (8.9%) patients presented with clinical features of a chronic CNS disease. Neurosyphilis, neurobrucellosis, neuroborreliosis, and CNS tuberculosis had a predilection to present chronic courses. Listeria monocytogenes, Staphylococcus aureus, M. tuberculosis, and S. pneumoniae were the most fatal forms, while sequelae were significantly higher for herpes simplex virus type 1 (p < 0.05 for all). Tackling the high burden of CNS infections globally can only be achieved with effective pneumococcal immunization and strategies to eliminate tuberculosis, and more must be done to improve diagnostic capacity.

Infections in travellers returning to Turkey from the Arabian peninsula: a retrospective cross-sectional multicenter study.

Mass gatherings pooling people from different parts of the world-the largest of which is to Mecca, Saudi Arabia, for Hajj-may impose risks for acquisition and dissemination of infectious diseases. A substantial number of pilgrims to Hajj and Umrah are Turkish citizens (456,000 in 2014) but data are lacking on scale of the problem. We did a retrospective cross-sectional multicenter study in Turkey to explore the range of infections among inpatients who had recently returned from the Arabian Peninsula. Our inclusion criteria were patients who had acquired an infection during their trip to an Arabian Peninsula country, or who became symptomatic within 1 week of their return. The data were collected retrospectively for January 1, 2013 and March 1, 2015. 185 Turkish patients were recruited to the study across 15 referral centers with travel associated infectious diseases after returning from Arabian Peninsula countries (predominantly Saudi Arabia 163 [88.1 %] for religious purposes 162 [87.5 %]). Seventy four (40.0 %) of them were ≥ 65 years old with numerous comorbidities including diabetes (24.3 %) and COPD (14.1 %). The most common clinical diagnosis was respiratory tract infections (169 [91.5 %]), followed by diarrheal diseases (13 [7 %]), and there was one case of MERS-CoV. Patients spent a median of 5 (3-7) days as hospital inpatients and overall mortality was 1.1 %. Returning travellers from the Arabian Peninsula present as inpatients with a broad range of infectious diseases similar to common community acquired infections frequently seen in daily medical practices in Turkey.

The clinical features, diagnosis, treatment, and prognosis of neuroinvasive listeriosis: a multinational study.

The aim of this study was to determine the independent risk factors, morbidity, and mortality of central nervous system (CNS) infections caused by Listeria monocytogenes. We retrospectively evaluated 100 episodes of neuroinvasive listeriosis in a multinational study in 21 tertiary care hospitals of Turkey, France, and Italy from 1990 to 2014. The mean age of the patients was 57 years (range, 19-92 years), and 64% were males. The all-cause immunosuppression rate was 54 % (54/100). Forty-nine (49 %) patients were referred to a hospital because of the classical triad of symptoms (fever, nuchal rigidity, and altered level of consciousness). Rhombencephalitis was detected radiologically in 9 (9 %) cases. Twenty-seven (64 %) of the patients who had cranial magnetic resonance imaging (MRI) performed had findings of meningeal and parenchymal involvement. The mean delay in the initiation of specific treatment was 6.8 ± 7 days. Empiric treatment was appropriate in 52 (52 %) patients. The mortality rate was 25 %, while neurologic sequelae occurred in 13 % of the patients. In the multivariate analysis, delay in treatment [odds ratio (OR), 1.07 [95 % confidence interval (CI), 1.01-1.16]] and seizures (OR, 3.41 [95 % CI, 1.05-11.09]) were significantly associated with mortality. Independent risk factors for neurologic sequelae were delay in treatment (OR, 1.07 [95 % CI, 1.006-1.367]) and presence of bacteremia (OR, 45.2 [95 % CI, 2.73-748.1]). Delay in the initiation of treatment of neuroinvasive listeriosis was a poor risk factor for unfavorable outcomes. Bacteremia was one of the independent risk factors for morbidity, while the presence of seizures predicted worse prognosis. Moreover, the addition of aminoglycosides to ampicillin monotherapy did not improve patients' prognosis.

Piperacillin/tazobactam vs. cefoperazone/sulbactam in adult low-risk febrile neutropenia cases.

AIM: The aim of this study was to compare the efficacy of piperacillin/tazobactam (P/T) and cefoperazone/sulbactam (C/S) in the empirical treatment of adult neutropenic fever. METHODS: Data and outcomes of low-risk adult cases with neutropenic fever and treated with P/T (4.5 g q6h) or C/S (2 g q8h) between 2005 and 2011 June were extracted from our database. Risk evaluation was made according to criteria of Multinational Association for Supportive Care in Cancer (MASCC) and a score of ≥ 21 was considered as low risk. Data were collected prospectively by daily visits and evaluated retrospectively. Primary outcome was - fever defervescence at 72 h in combination with success without modification (referring to episodes where the patient recovered from fever with disappearance of signs of infection without modification to initial empirical treatment). All-cause mortality referred to death resulting from a documented or presumed infection or unidentified reason during the treatment and 30-day follow-up period. RESULTS: A total of 172 patients (113 cases P/T and 59 cases C/S) fulfilled the study inclusion criteria. Persistent response in P/T arm was 73.5%, whereas it was 64.5% in C/S arm (p > 0.05). Rates of any modification were also similar in both treatment arms. All-cause mortality during the treatment and 30-day follow-up period was not significantly different (P/T: 4/113 vs. C/S: 2/59, p > 0.05). There was no severe adverse effect requiring antibiotic cessation in both cohorts. CONCLUSION: In conclusion, our data suggest that C/S may be a safe alternative to P/T in the empirical treatment of adult low-risk febrile neutropenia cases.

Nursing students' immunisation status and knowledge about viral hepatitis in Turkey: a multi-centre cross-sectional study.

BACKGROUND: The aims of this multi-centre cross-sectional survey were to detect Turkish nursing students' level of knowledge on viral hepatitis, to evaluate their rates of exposure to blood and to find out their hepatitis A (HAV), hepatitis B (HBV) vaccination status. METHODS: This multi-centre cross-sectional study was conducted in 14 nursing schools located in the seven geographical regions of Turkey. A questionnaire composed of 47 questions on socio-demographic factors, level of knowledge on HAV, HBV, hepatitis C (HCV) immunisation status, exposure history and attitudes was applied to the study group. RESULTS: A total of 1491 third- and fourth-year nursing students participated with an 89% response rate. The mean age of the participating students was 21.4 ± 1.3. Their mean knowledge score was 23.7 ± 4.6 (71/100) and was significantly higher in fourth-year students than third-year students. There were significant differences in mean scores among nursing schools. Among the participants, 85.3% had received HBV vaccine and 9.1% had received HAV vaccine. The percentage of students who signify themselves at increased risk of acquiring viral hepatitis was 97.3%. Of the students, 28.1% had sustained a needle-stick injury and 5.4% had experienced conjunctival exposure to blood. CONCLUSIONS: Curriculum differences among nursing schools have a significant effect on nursing students' level of knowledge. For this reason, nursing schools should organize HBV immunisation programmes for their students to increase vaccination coverage.

Daptomycin versus teicoplanin in the treatment of osteomyelitis: Results of the Göztepe retrospective cohort study.

OBJECTIVES: Daptomycin is highly effective against Gram-positive multidrug-resistant bacteria. Publications on daptomycin in osteomyelitis treatment are limited. PATIENTS AND METHODS: In this multicenter retrospective cohort study, the aim was to evaluate the outcomes of osteomyelitis cases having received daptomycin or teicoplanin. This multicenter retrospective cohort study gathered data from seven centers located in five cities of Turkey. Study inclusion criteria were as follows: (a) magnetic resonance imaging and/or direct X-ray revealed osteomyelitis or biopsy pathologic examination results concomitant with osteomyelitis. Chi-squareand Student t-tests were used for statistical comparison. RESULTS: A total of 72 patients, 38 cases in the daptomycin group and 34 cases in the teicoplanin group diagnosed with osteomyelitis fulfilling the study inclusion criteria, were included in the study. Clinical success at the end of induction therapy was achieved in 32/38 cases in the daptomycin cohort vs. 30/34 cases in the teicoplanin cohort (p: 0.73). CONCLUSION: Although this is a limited experience in a small but well-defined cohort, our data suggest that daptomycin may be a safe alternative to glycopeptides in osteomyelitis treatment. A randomized controlled clinical study involving larger cohorts may increase the available evidence.

Tigecycline-based prolonged salvage therapy in patients presenting with complex bone and joint infection.

OBJECTIVES: To assess the clinical experience of tigecycline-based salvage therapy in patients presenting with Bone and Joint Infections (BJI). PATIENTS AND METHODS: Multicenter retrospective cohort study in France and Turkey (2007-2014). RESULTS: Thirty-six patients (age 58.2±17.8 years; 21 men) were included. The most frequently isolated bacteria were Enterobacteriaceae and staphylococci. Tigecycline (50mg BID, mainly in combination (69.4%), mean duration of 58 days) was indicated for multidrug resistance (90.6%) and/or previous antibiotic intolerance (36.1%), and/or as second- or third-line therapy (69.4%). Six patients (16.7%) experienced early treatment discontinuation for adverse event (4 severe vomiting, 1 pancreatitis, 1 asymptomatic lipase increase). Clinical success was observed in 23 of 30 assessable patients who completed the tigecycline therapy (mean follow-up: 54.1±57.7 weeks). CONCLUSION: Prolonged tigecycline-based therapy could be an alternative in patients presenting with BJI requiring salvage therapy, especially if multidrug-resistant Enterobacteriaceae and/or staphylococci are involved.

Managing atypical and typical herpetic central nervous system infections: results of a multinational study.

There have been many studies pertaining to the management of herpetic meningoencephalitis (HME), but the majority of them have focussed on virologically unconfirmed cases or included only small sample sizes. We have conducted a multicentre study aimed at providing management strategies for HME. Overall, 501 adult patients with PCR-proven HME were included retrospectively from 35 referral centres in 10 countries; 496 patients were found to be eligible for the analysis. Cerebrospinal fluid (CSF) analysis using a PCR assay yielded herpes simplex virus (HSV)-1 DNA in 351 patients (70.8%), HSV-2 DNA in 83 patients (16.7%) and undefined HSV DNA type in 62 patients (12.5%). A total of 379 patients (76.4%) had at least one of the specified characteristics of encephalitis, and we placed these patients into the encephalitis presentation group. The remaining 117 patients (23.6%) had none of these findings, and these patients were placed in the nonencephalitis presentation group. Abnormalities suggestive of encephalitis were detected in magnetic resonance imaging (MRI) in 83.9% of the patients and in electroencephalography (EEG) in 91.0% of patients in the encephalitis presentation group. In the nonencephalitis presentation group, MRI and EEG data were suggestive of encephalitis in 33.3 and 61.9% of patients, respectively. However, the concomitant use of MRI and EEG indicated encephalitis in 96.3 and 87.5% of the cases with and without encephalitic clinical presentation, respectively. Considering the subtle nature of HME, CSF HSV PCR, EEG and MRI data should be collected for all patients with a central nervous system infection.

The microbiological diagnosis of tuberculous meningitis: results of Haydarpasa-1 study.

We aimed to provide data on the diagnosis of tuberculous meningitis (TBM) in this largest case series ever reported. The Haydarpasa-1 study involved patients with microbiologically confirmed TBM in Albania, Croatia, Denmark, Egypt, France, Hungary, Iraq, Italy, Macedonia, Romania, Serbia, Slovenia, Syria and Turkey between 2000 and 2012. A positive culture, PCR or Ehrlich-Ziehl-Neelsen staining (EZNs) from the cerebrospinal fluid (CSF) was mandatory for inclusion of meningitis patients. A total of 506 TBM patients were included. The sensitivities of the tests were as follows: interferon-γ release assay (Quantiferon TB gold in tube) 90.2%, automated culture systems (ACS) 81.8%, Löwenstein Jensen medium (L-J) 72.7%, adenosine deaminase (ADA) 29.9% and EZNs 27.3%. CSF-ACS was superior to CSF L-J culture and CSF-PCR (p <0.05 for both). Accordingly, CSF L-J culture was superior to CSF-PCR (p <0.05). Combination of L-J and ACS was superior to using these tests alone (p <0.05). There were poor and inverse agreements between EZNs and L-J culture (κ = -0.189); ACS and L-J culture (κ = -0.172) (p <0.05 for both). Fair and inverse agreement was detected for CSF-ADA and CSF-PCR (κ = -0.299, p <0.05). Diagnostic accuracy of TBM was increased when both ACS and L-J cultures were used together. Non-culture tests contributed to TBM diagnosis to a degree. However, due to the delays in the diagnosis with any of the cultures, combined use of non-culture tests appears to contribute early diagnosis. Hence, the diagnostic approach to TBM should be individualized according to the technical capacities of medical institutions particularly in those with poor resources.

Is tigecyclin a good choice in the treatment of multidrug-resistant Acinetobacter baumannii pneumonia?

The aim of this study was to evaluate the efficacy of tigecycline in multidrug-resistant (MDR) Acinetobacter baumannii pneumonia. We retrospectively evaluated the outcome of adult patients with culture proven MDR A. baumannii pneumonia treated with tigecycline between January 2009 and March 2011. The study comprised a total of 72 MDR A. baumannii pneumonia cases (44 men, mean age 65.9±15.0). Tigecycline was used for a mean duration of 10.7±4.8 days. Microbiological eradication was observed in 47 cases (65.3%). Overall mortality was 55.5% and was lower in cases with microbiological eradication vs others (15/47 32% vs 25/25 100%, p<0.0001). Mortality and microbiological eradication rates were not different with monotherapy vs combination therapy (p>0.05). Patients who died had lower albumin levels, higher APACHE-II scores and CRP levels. The microbiological eradication rate of tigecycline in MDR A. baumannii was considerable. However, eradication of A. baumannii did not result in favorable clinical outcomes in those patients with low albumin, higher APACHE-II scores and CRP levels.

Carbapenem versus fosfomycin tromethanol in the treatment of extended-spectrum beta-lactamase-producing Escherichia coli-related complicated lower urinary tract infection.

The aim of this observational prospective study was to compare the effect of fosfomycin tromethanol (FT) and carbapenems (meropenem or imipenem cilastatin) in the treatment of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli-related complicated lower urinary tract infection (CLUTI). Inclusion criteria were: patients who were aged >18 yr with dysuria or problems with frequency or urgency in passing urine; those with >20 leukocytes/mm³ in urine microscopy and culture-proven ESBL-producing carbapenem or FT-sensitive E. coli in the urine (>105 cfu/mm³); no leukocytosis or fever; and who were treated with ft (oral 3 g sachet x 1 every other night, three times) or carbapenems between march 2005 and January 2006 in our outpatient clinic and hospital. A total of 47 CLUTI attacks in 47 patients (27 FT group, 20 carbapenem group) were observed prospectively. Clinical and microbiological success in the carbapenem and ft groups was similar (19/20 vs 21/27 and 16/20 vs 16/27 p>0.05). Drug acquisition costs were significantly lower in the FT group (p<0.001). Although it is not a randomized controlled study, these data show that ft may be a suitable, effective and cheap alternative in the treatment of ESBL-producing E. coli-related CLUTI.