Multidrug-resistant Gram-negative osteomyelitis: a 10-year study.

AIM: Few series of osteomyelitis due to multi-drug (MDR) or extensively-drug resistant (XDR) gram-negative bacteria exist. A retrospective study of MDR and XDR gram-negative osteomyelitis cases was performed, aiming to investigate causative organisms, proper surgical and medical management, as well as outcome. PATIENTS AND METHODS: All patients, treated at the University hospital of Crete between 2007 and 2016 for acute osteomyelitis, due to MDR or XDR gram-negative pathogens were evaluated. RESULTS: A total of 14 patients (8 males) were identified with a mean age of 50.6 years. Five Acinetobacter baumanii cases, 3 XDR and 2 MDR, were found. Furthermore, 3 MDR Klebsiella pneumoniae and 3 MDR Enterobacter cloacae isolates were identified. Additionally, 2 MDR Escherichia coli, as well as 2 Pseudomonas aeruginosa, 1 XDR and 1 MDR, were isolated. One case of Roseomonas gilardii was also identified. In 5 cases the same pathogen was also isolated from blood. Five out of the 14 patients were smokers, 6 were suffering severe injury, 4 had diabetes-mellitus, 2 chronic renal disease and 2 were obese. Most causative organisms had hospital origin. All patients received first line empirical combination antimicrobial treatment, proven effective in 4. Thirteen patients were also subjected to surgical treatment. The study included mainly young individuals, most likely due to the high incidence of traffic accidents involving young adults in Crete. CONCLUSIONS: Antimicrobial regimens are important supplements to surgical treatment of acute osteomyelitis. However, due to emergence of resistant microorganisms, compliance with strict rules of antimicrobial strategy is of utmost importance.

Heterogeneity of circulating tumor cells (CTCs) in patients with recurrent small cell lung cancer (SCLC) treated with pazopanib.

OBJECTIVES: To investigate the effect of pazopanib on different CTCs subpopulations in patients with recurrent SCLC and evaluate their clinical relevance. METHODS: Peripheral blood was obtained before the administration of pazopanib (n=56 patients), after the first cycle (n=35 patients) and at disease progression (n=45 patients). CTCs were detected by CellSearch and double immunofluorescent staining using antibodies against the cytokeratins (CK), TTF-1, CD56 and VEGFR2. RESULTS: Before treatment, CTCs could be detected in 50% of patients by CellSearch; phenotypic characterization of CTCs demonstrated that 50%, 46.6% and 27.6% of patients had CD45-/TTF1+, CD45-/CD56+ and TTF-1+/CD56+ CTCs, respectively. Additionally, 59% of CTCs were TTF-1+/VEGFR2+ and 53% CK+/VEGFR2+. One pazopanib cycle resulted to a significant decrease of the number of CTCs (CellSearch: p=0.043) and CK+/VEGFR2+ cells (p=0.027). At the time of PD, both the total number of CTCs (p=0.027) and the number of the different subpopulations were significantly increased compared to post-1st cycle values; this increased CTCs number was associated with a significant increase of TTF-1+/VEGFR2+ (p=0.028) and CK+/VEGFR2+ CTCs (p=0.018). In multivariate analysis, only the number of CTCs as assessed by CellSearch after one treatment cycle was significantly associated with OS (HR: 0.21; p=0.005). CONCLUSIONS: Pazopanib has a significant effect on different subpopulations of CTCs in patients with relapsed SCLC; the detection of VEGFR2+ CTCs during treatment could be a surrogate marker associated with resistance to pazopanib.

Patient-ventilator synchrony and sleep quality with proportional assist and pressure support ventilation.

OBJECTIVE: To examine patient-ventilator asynchrony and sleep quality in non-sedated critically ill patients ventilated with proportional assist ventilation with load adjustable gain factors (PAV+) and pressure support (PSV). METHODS: This was a randomized crossover physiological study conducted in an adult ICU at a tertiary hospital. Patients who exhibited patient-ventilator asynchrony on PSV were selected. Polysomnography was performed in these patients over 24 h, during which respiratory variables were continuously recorded. During the study period, each patient was randomized to receive alternating 4-h periods of PSV and PAV+ equally distributed during the day and night. Sleep architecture was analyzed manually using predetermined criteria. Patient-ventilator asynchrony was evaluated breath by breath using the flow-time and airway pressure-time waveforms. RESULTS: Fourteen patients were studied. The majority (85.7 %) had either acute exacerbation of COPD as admission diagnosis or COPD as comorbidity. During sleep, compared to PSV, PAV+ significantly reduced the patient-ventilator asynchrony events per hour of sleep [5 (1-17) vs. 40 (4-443), p = 0.02, median (25-75th interquartile range)]. Compared to PSV, PAV+ was associated with slightly but significantly greater sleep fragmentation [18.8 (13.1-33.1) versus 18.1 (7.0-22.8) events/h, p = 0.01] and less REM sleep [0.0 % (0.0-8.4) vs. 5.8 % (0.0-21.9), p = 0.02). CONCLUSIONS: PAV+ failed to improve sleep in mechanically ventilated patients despite the fact that this mode was associated with better synchrony between the patient and ventilator. These results do not support the hypothesis that patient-ventilator synchrony plays a central role in determining sleep quality in this group of patients.

Airway neutrophilia in COPD is not associated with increased neutrophil survival.

Neutrophilic airway inflammation is a prominent feature of chronic obstructive pulmonary disease (COPD) and correlates with disease severity. The mechanisms that determine the extent of neutrophilia could involve increased influx or prolonged survival of neutrophils. The aim of the study was to assess whether neutrophil pro-survival mechanisms are increased in the airways of subjects with COPD owing to the presence of anti-apoptotic factors in the bronchial lining fluid. Induced sputum samples were collected from 20 subjects with stable COPD, 14 healthy smokers and 14 healthy controls. Quantification of apoptotic neutrophils was based on typical morphological cell changes. Anti-apoptotic, pro-survival activity in the sputum was studied by culturing peripheral blood neutrophils with the fluid phase of induced sputum. Apoptosis was assessed both by morphology and flow cytometry using Annexin V/7-aminoactinomycin D staining. COPD patients and healthy smokers had significantly higher percentages of sputum neutrophils than healthy controls. However, there were no significant differences between the three subject groups in either the proportion of apoptotic neutrophils in sputum or the in vitro anti-apoptotic activity detected in the sputum fluid phase. In conclusion, prolonged survival of neutrophils in sputum is not a feature of chronic obstructive pulmonary disease and cannot explain the increased numbers of airway neutrophils in this disease.

Availability of antidotes in hospital pharmacies in Greece.

We determined the availability of poisoning antidotes in the pharmacies of state hospitals in Greece and in Health Centers of the island of Crete. A questionnaire survey was sent to all pharmacy directors of hospitals with emergency departments, asking them to report anonymously the amount currently in stock of each of 12 common antidotes. Questionnaires were sent to 100 pharmacy directors and 68 (68%) of them replied. Only 2 (3%) of the 68 hospitals stocked all 12 antidotes. The percentage of sufficient stocking for individual antidotes ranged from 6% (for digoxin immune fab) to 91% (for methylene blue). Recent circulation of government guidelines for antidote stocking and hospital type had no significant effect on antidote stocking. In a multiple regression analysis, hospital type (prefectural, regional, university hospital) and smaller hospital size were not predictors of the number of antidotes sufficiently stocked. Storing of key poisoning antidotes is inadequate in regional as well as in prefectural hospitals in Greece. Antidotes, including those which should be used without delay to be effective, are often not available, even for the commoner poisons in Greece such as pesticides.

Ceftriaxone and dexamethasone affecting yeast gut flora in experimental mice.

Crl:CD1 (ICR) BR mice were fed regular food or food containing Candida albicans to induce gastrointestinal (GI) colonization by the yeast. Groups of colonized mice were subsequently treated with either ceftriaxone for 10 days or dexamethasone for 10 or 21 days. Another group of colonized mice was treated with the combination of ceftriaxone, given for 10 days, and dexamethasone given for 21 days. Other colonized mice received normal saline, and non-colonized mice received the same drugs or saline, serving as controls. Candida-colonized mice, treated either with ceftriaxone or with dexamethasone alone, had significantly increased levels of GI colonization by the yeast. Colonized mice treated with the combination of the antibiotic with dexamethasone had stool concentrations of Candida similar to those of mice treated with the antibiotic alone. Saline did not affect Candida stool concentration. Yeasts were not found in the stools of non-colonized mice treated with the study drugs or saline. There was no evidence of Candida dissemination to internal organs in any group.

Effects of cefepime, cefixime and ceftibuten on murine gut colonization by Candida albicans.

Crl:CD1(ICR) BR mice were fed chow containing Candida albicans or regular chow. Both groups were subsequently given either antibiotics or normal saline. Stool cultures were performed before, at the end of treatment and 1 week after treatment, to determine the effect on the stool yeast concentration. Candida-colonized mice treated with cefepime, cefixime or ceftibuten had higher (however not significantly) counts of the yeast in their stools than control Candida-fed mice treated with saline. A group of Candida-fed mice were treated with ceftriaxone, which is known to increase the yeast stool concentration significantly and served as positive control. Mice fed regular chow and treated with the study drugs or saline did not have any yeasts in their stools. Dissemination of Candida did not occur.