Co-infections and superinfections complicating COVID-19 in cancer patients: A multicentre, international study.

BACKGROUND: We aimed to describe the epidemiology, risk factors, and clinical outcomes of co-infections and superinfections in onco-hematological patients with COVID-19. METHODS: International, multicentre cohort study of cancer patients with COVID-19. All patients were included in the analysis of co-infections at diagnosis, while only patients admitted at least 48 h were included in the analysis of superinfections. RESULTS: 684 patients were included (384 with solid tumors and 300 with hematological malignancies). Co-infections and superinfections were documented in 7.8% (54/684) and 19.1% (113/590) of patients, respectively. Lower respiratory tract infections were the most frequent infectious complications, most often caused by Streptococcus pneumoniae and Pseudomonas aeruginosa. Only seven patients developed opportunistic infections. Compared to patients without infectious complications, those with infections had worse outcomes, with high rates of acute respiratory distress syndrome, intensive care unit (ICU) admission, and case-fatality rates. Neutropenia, ICU admission and high levels of C-reactive protein (CRP) were independent risk factors for infections. CONCLUSIONS: Infectious complications in cancer patients with COVID-19 were lower than expected, affecting mainly neutropenic patients with high levels of CRP and/or ICU admission. The rate of opportunistic infections was unexpectedly low. The use of empiric antimicrobials in cancer patients with COVID-19 needs to be optimized.

Impact of the Inclusion of an Aminoglycoside to the Initial Empirical Antibiotic Therapy for Gram-Negative Bloodstream Infections in Hematological Neutropenic Patients: a Propensity-Matched Cohort Study (AMINOLACTAM Study).

To test the hypothesis that the addition of an aminoglycoside to a ß-lactam antibiotic could provide better outcomes than ß-lactam monotherapy for the initial empirical treatment of hematological neutropenic patients with subsequently documented Gram-negative bacillus (GNB) bloodstream infection (BSI), a multinational, retrospective, cohort study of GNB BSI episodes in hematological neutropenic patients in six centers (2010 to 2017) was conducted. Combination therapy (ß-lactam plus aminoglycoside) was compared to ß-lactam monotherapy. The primary endpoint was the case fatality rate, assessed at 7 and 30 days from BSI onset. Secondary endpoints were nephrotoxicity and persistent BSI. Propensity score (PS) matching was performed. Among 542 GNB BSI episodes, 304 (56%) were initially treated with combination therapy, with cefepime plus amikacin being most common (158/304 [52%]). Overall, Escherichia coli (273/304 [50.4%]) was the main etiological agent, followed by Pseudomonas aeruginosa, which predominated in the combination group (76/304 [25%] versus 28/238 [11.8%]; P < 0.001). Multidrug resistance rates were similar between groups (83/294 [28.2%] versus 63/233 [27%]; P = 0.95). In the multivariate analysis, combination therapy was associated with a lower 7-day case fatality rate (odds ratio [OR], 0.37; 95% CI, 0.14 to 0.91; P = 0.035) with a tendency toward lower mortality at 30 days (OR, 0.56; 95% CI, 0.29 to 1.08; P = 0.084). After PS matching, these differences remained for the 7-day case fatality rate (OR, 0.33; 95% CI, 0.13 to 0.82; P = 0.017). In addition, aminoglycoside use was not significantly associated with renal function impairment (OR, 1.12; 95% CI, 0.26 to 4.87; P = 0.9). The addition of an aminoglycoside to the initial empirical therapy regimen for febrile neutropenic hematological patients should be considered.

Mixed fungaemia: an 18-year report from a tertiary-care university hospital and a systematic review.

BACKGROUND: While fungaemia caused by two or more different species of yeasts (mixed fungaemia, MF) is infrequent, it might be underestimated. AIMS: This study aimed to determine the incidence of MF, clinical characteristics of the patients, and antifungal susceptibility profiles of the isolates with a systematic review of the literature. SOURCES: Data sources were PubMed and Scopus. STUDY ELIGIBILITY CRITERIA: Studies reporting ten or more mixed fungaemia episodes. CONTENT: Study included MF episodes in adults between January 2000 and August 2018 in Hacettepe University Hospitals, Turkey. The isolation, identification and antifungal susceptibility testing (AFST) of the isolates were by standard mycological methods. Patient data were obtained retrospectively. Literature search was performed using relevant keywords according to PRISMA systematic review guidelines. A total of 32 patients with 33 MF episodes were identified. Among all fungaemia episodes, MF incidence was 3.7% (33/883). All patients had one or more underlying disorders among which solid-organ cancer (50.0%, 16/32) was the most common. Overall mortality was 51.5% (17/33). The most preferred antifungal agents for initial treatment were fluconazole (48.5%, 16/33) and echinocandins (39.4%, 13/33). Fluconazole susceptible-dose-dependent (S-DD) or -resistant Candida species were detected in 15 episodes, and an isolate of C. parapsilosis was classified as S-DD by AFST. All Candida isolates were susceptible to echinocandins. Non-candida yeasts with intrinsic resistance/reduced susceptibility to both echinocandins and fluconazole were detected in two episodes. Systematic review of the literature revealed 24 studies that reported more than ten MF episodes. Methodology was variable. Improvement of detection rates was reported when chromogenic agars were used. Most studies underlined detection of isolates with reduced susceptibility. IMPLICATIONS: Although rare, the MF rate is affected by the detection methods, which have improved in recent years. Fluconazole and echinocandins were used for initial treatment in accordance with the current guideline recommendations; however, isolates non-susceptible to both were detected. Detection of a mixed infection offers an opportunity for optimum treatment.

Risk factors for typhoid fever among adult patients in Diyarbakir, Turkey.

We conducted a case-control study to assess risk factors for typhoid fever in Diyarbakir, Turkey, a region where transmission of Salmonella typhi is endemic. We prospectively identified febrile patients from Diyarbakir and the surrounding area who were admitted to hospital. Cases were defined as patients who had S. typhi isolated from at least one blood culture. Sixty-four cases with blood culture-confirmed S. typhi were identified between May 2001 and May 2003. In total, 128 age- and sex-matched controls selected from neighbourhoods as cases were enrolled. We hypothesized that consumption of raw vegetables contaminated with sewage would be associated with an increased risk of typhoid fever. Conditional logistic regression modelling revealed that living in a crowded household (OR 3.31, 95% CI 1.58-6.92, P=0.002), eating cig kofte (a traditional raw food) (OR 5.29, 95% CI 2.20-12.69, P=0.000) and lettuce salad (OR 3.55, 95% CI 1.52-8.28, P=0.003) in the 15 days prior to symptoms onset was independently associated with typhoid fever. We conclude that living in a crowded household and consumption of raw vegetables outside the home increase the risk of typhoid fever in this region.

Tuberculous meningitis in adults in Turkey: epidemiology, diagnosis, clinic and laboratory [corrected].

A retrospective study was performed to assess the epidemiology, diagnosis, clinic, and laboratory of the patients with tuberculous meningitis (TBM) in a multicentral study. The medical records of adult cases with TBM treated at 12 university hospitals throughout Turkey, between 1985 and 1998 were reviewed using a standardized protocol. The diagnosis of TMB was established with the clinical and laboratory findings and/or microbiological confirmation in cerebrospinal fluid (CSF). The non-microbiologically confirmed cases were diagnosed with five diagnostic sub-criteria which CSF findings, radiological findings, extra-neural tuberculosis, epidemiological findings and response to antituberculous therapy. A total of 469 patients were included in this study. Majority of the patients were from Southeast Anatolia (164 patients, 35.0%) and (108 patients, 23.0%) from East Anatolia regions. There was a close contact with a tuberculous patient in 88 of 341 patients (25.8%) and with a tuberculous family member in 53 of 288 patients (18.4%). BCG scar was positive in 161 of 392 patients (41.1%). Tuberculin skin test was done in 233 patients and was found to be negative in 75. Totally 115 patients died (24.5%) of whom 23 died in 24 hour after admittance. The diagnosis was confirmed with clinical findings and CSF culture and/or Ziehl-Nelson staining in 88 patients (18.8%). Besides clinical criteria, there were three or more diagnostic sub-criteria in 252 cases (53.7%), two diagnostic sub-criteria in 99 cases (21.1%), and any diagnostic sub-criteria in 30 patients (6.4%). Since TBM is a very critical disease, early diagnosis and treatment may reduce fatal outcome and morbidity.

Tuberculous meningitis in adults: an eleven-year review.

OBJECTIVE: To assess the presentation, diagnosis and outcome of patients with tuberculous meningitis (TBM). DESIGN: The medical records of adults with TBM who were treated at Dicle University Hospital between January 1985 and October 1996 were reviewed. RESULTS: In total, 101 patients were identified and stratified according to the stage of disease at presentation. The mean duration of the symptoms of TBM before admission was 12 days. The majority of patients had headaches (96.0%), fever (91.1%), nuchal rigidity (91.1%), vomiting (81.2%), meningism (79.2%) and abnormal mental state (72.3%). The mean cerebrospinal fluid (CSF) leukocyte count was 0.38 x 10(9)/L, protein 1410 mg/L, glucose 2.0 mmol/L and CSF/blood glucose ratio 27%. Cranial computerized tomography (CT) scans were performed during the course of TBM in 64 patients. The results were normal in 6.3%, and abnormal in 93.7% of the cases; the most frequent abnormality found on CT was hydrocephalus (45.3%). Forty-four patients (43.5%) died. Minor neurological sequelae developed in 11 patients (10.9%), major sequelae in 10 (9.9%), and 31 patients (30.7%) completely recovered. There was no follow-up for five patients (5.0%). Five factors were important in predicting fatal outcome: stage III at presentation, low glucose levels, low CSF/blood glucose ratio, high protein levels, and CT scanning abnormality. CONCLUSION: TBM is a very critical disease in terms of fatal outcome and permanent sequelae: 43.5% of the patients died and only 30.7% experienced complete recovery. Early treatment may reduce fatal outcome and morbidity.

Acute bacterial meningitis in adults: analysis of 218 episodes.

A retrospective study was conducted to examine the laboratory, clinical features and outcome of 206 adult acute bacterial meningitis patients (218 episodes) during the years 1985-1996. Pneumonia (8.7 per cent), head trauma (7.8 per cent) and chronic otitis media (6.0 per cent) were identified as the main predisposing factors for acute bacterial meningitis. Aetiology was described only in 61 episodes (28.0 per cent). Streptococcus pneumonia was the most commonly identified pathogen overall, causing 33 of the 218 episodes (15.2 per cent). Antibiotic treatment before admission was given to 48.4 per cent of patients. On admission, the following symptoms of meningitis were predominant: 83 per cent had neck stiffness, 81 per cent had a headache and 73 per cent had fever. Case fatality rate was 27.1 per cent (59 patients). The important factors in mortality were as follows: old age, a long duration of symptoms before admission, a lack of neck stiffness, obtunded mental state on admission, low glucose levels in first CSF, low CSF/blood glucose ratio, and abnormality in computerised tomography scanning.

Recurrent bacterial meningitis: a 6-year experience in adult patients.

Ten adult patients with recurrent bacterial meningitis (RBM) of 22 episodes were diagnosed and treated at the Dicle University Hospital from January 1990 to December 1995. Apart from 22 episodes of RBM these patients had an additional 25 episodes treated at other hospitals. The RBM attacks developed after closed head trauma in four patients, asplenia and chronic otitis media in one patient, chronic otitis media and oto-mastoiditis in one patient, chronic maxillary sinusitis in one patient, chronic mastoiditis in one patients, and suppurative foci of facial bones caused by shrapnel pieces and no predisposing condition in one patient. In 10 RBM episodes, Streptococcus pneumoniae was isolated from cerebrospinal fluid (CSF) and/or blood culture, and in one episode Proteus vulgaris was isolated from CSF and otitis media suppuration. In the four episodes both cultures were negative, but direct microscopy showed Gram-positive diplococci on Gram-staining. Three of the patients died from meningitis-related complications.

Effects of nimodipine on the cerebrovascular and neuronal changes during pneumococcal meningitis in the rat.

It was investigated whether treatment with the calcium channels blocker Nimodipine, a 1,4-dihydropyridine derivative, influences vasculopathy and neuronal injury in experimental pneumococcal meningitis. Rats were randomly assigned to one of three experimental groups. The first group (Control group, n = 20) was given saline (0.4 ml/day) intraperitoneally (i.p.), whereas the second group (group C, n = 22) was treated only with ceftriaxone in a dosage of 30 mg/day/i.p.. The third group (group C-N, n = 22) was treated with the combination of ceftriaxone 30 mg/day/i.p., and nimodipine 0.6 mg/day/i.p.. Treatment was begun at the time of inoculation in all three groups. The control group was compared clinically and histopathologically with groups C and C-N at 24 h, three and six days after inoculation. Six rats in the control group and eight rats in group C and group C-N were sacrificed at 24 hours and seven rats in each group were sacrificed on the third and sixth day after inoculation. Clinically, there were no significant differences between group C and group C-N (p>0.05). There were significant differences between group C and group C-N for vasculopathy and neuronal injury (p < 0.0001 and p < 0.005, respectively).