Genetic polymorphisms within tumor necrosis factor gene promoter region: a role for susceptibility to ventilator-associated pneumonia.

Debatable findings exist among various studies regarding the impact of single nucleotide polymorphisms (SNPs) within the promoter region of the tumor necrosis factor (TNF) gene for susceptibility to infections. Their impact was investigated in a cohort of mechanically ventilated patients who developed ventilator-associated pneumonia (VAP). Two-hundred and thirteen mechanically ventilated patients who developed VAP were enrolled. Genomic DNA was extracted and SNPs at the -376, -308 and -238 position of the promoter region of the TNF gene were assessed by restriction fragment length polymorphisms. Monocytes were isolated from 47 patients when they developed sepsis and stimulated by bacterial endotoxin for the production of TNFα and of interleukin-6 (IL-6). Patients were divided into two groups; 166 patients bearing only wild-type alleles of all three studied polymorphisms; and 47 patients carrying at least one A allele of the three studied SNPs. Time between start of mechanical ventilation and advent of VAP was significantly shorter in the second group than in the first group (log-rank: 4.416, p: 0.041). When VAP supervened, disease severity did not differ between groups. Stimulation of TNFα and of IL-6 was much greater by monocytes for patients carrying A alleles. Carriage of at least one A allele of the three studied SNPs at the promoter region of the TNF-gene is associated with shorter time to development of VAP but it is not associated with disease severity. Findings may be related with a role of the studied SNPs in the production of pro-inflammatory cytokines.

Risk assessment in sepsis: a new prognostication rule by APACHE II score and serum soluble urokinase plasminogen activator receptor.

INTRODUCTION: Early risk assessment is the mainstay of management of patients with sepsis. APACHE II is the gold standard prognostic stratification system. A prediction rule that aimed to improve prognostication by APACHE II with the application of serum suPAR (soluble urokinase plasminogen activator receptor) is developed. METHODS: A prospective study cohort enrolled 1914 patients with sepsis including 62.2% with sepsis and 37.8% with severe sepsis/septic shock. Serum suPAR was measured in samples drawn after diagnosis by an enzyme-immunoabsorbent assay; in 367 patients sequential measurements were performed. After ROC analysis and multivariate logistic regression analysis a prediction rule for risk was developed. The rule was validated in a double-blind fashion by an independent confirmation cohort of 196 sepsis patients, predominantly severe sepsis/septic shock patients, from Sweden. RESULTS: Serum suPAR remained stable within survivors and non-survivors for 10 days. Regression analysis showed that APACHE II ≥ 17 and suPAR ≥ 12 ng/ml were independently associated with unfavorable outcome. Four strata of risk were identified: i) APACHE II <17 and suPAR <12 ng/ml with mortality 5.5%; ii) APACHE II < 17 and suPAR ≥ 12 ng/ml with mortality 17.4%; iii) APACHE II ≥ 17 and suPAR <12 ng/ml with mortality 37.4%; and iv) APACHE II ≥ 17 and suPAR ≥ 12 ng/ml with mortality 51.7%. This prediction rule was confirmed by the Swedish cohort. CONCLUSIONS: A novel prediction rule with four levels of risk in sepsis based on APACHE II score and serum suPAR is proposed. Prognostication by this rule is confirmed by an independent cohort.

Susceptibility profiles and clinical efficacy of antifungals against candida bloodstream isolates from critically ill patients: Focus on intravenous itraconazole.

In vitro and clinical data were analysed to evaluate the susceptibility profile of itraconazole in light of the new cut-off points. The in vitro activity of itraconazole was compared with that of eight comparators against 119 Candida bloodstream isolates from 2015 to 2018. Minimum inhibitory concentrations (MICs) were measured by the colorimetric MICRONAUT-S assay. The content of wells without any color change was sub-cultured to measure killing efficacy. No major differences were found against Candida albicans. Itraconazole, posaconazole and amphotericin B were the most active agents against Candida parapsilosis. Of the 32 isolates of C. parapsilosis that were resistant to fluconazole, 96.9%, 78.1% and 93.8% were susceptible to itraconazole, voriconazole and posaconazole, respectively. The ratio of the minimum fungicidal concentration (MFC) to the MIC of itraconazole was lower than for the other azoles against C. parapsilosis and C. glabrata. Itraconazole achieved greater inhibition over-time of the growth of C. parapsilosis than fluconazole. Seventy-three critically ill patients who were unresponsive to antibiotics received intravenous empirical treatment with itraconazole (n = 28) or comparators (n = 45). Case-control matching was conducted for severity, comorbidities, risk factors for candidemia, administered antibiotics and days of antifungal treatment. Breakthrough candidemia was found in 3.6% of patients treated with itraconazole and in 32.1% of patients treated with comparators (P: 0.020); breakthrough candidemia by C. parapsilosis was found in 3.6% and 28.6% of patients, respectively. Results indicate that itraconazole retains a valuable susceptibility profile against Candida isolates, particularly C. parapsilosis. This superior profile may explain the clinical efficacy in the occurrence of breakthrough candidemia and warrants further clinical investigation.

Rhinocerebral mucormycosis in a patient with cirrhosis and chronic renal failure.

Mucormycosis is an opportunistic fungal infection caused by Mucorales. The disease is uncommon and produces serious and rapidly fatal infection in diabetic or immunocompromised patients. The classical presentation of rhinocerebral mucormycosis is involvement of nasal mucosa with invasion of paranasal sinuses and orbit. Early diagnosis is based on (direct) histological examination and computed tomography scan. Unfortunately the clinical signs and symptoms do not occur in all cases. A high index of suspicion is needed not only in typical groups of immunocompromised patients or diabetics, but also in patients with serious chronic diseases. We report a patient who was not diabetic, but she had a history of cirrhosis and well compensated renal failure.

Early changes of procalcitonin may advise about prognosis and appropriateness of antimicrobial therapy in sepsis.

PURPOSE: The objective of this study is to define if early changes of procalcitonin (PCT) may inform about prognosis and appropriateness of administered therapy in sepsis. METHODS: A prospective multicenter observational study was conducted in 289 patients. Blood samples were drawn on day 1, that is, within less than 24 hours from advent of signs of sepsis, and on days 3, 7, and 10. Procalcitonin was estimated in serum by the ultrasensitive Kryptor assay (BRAHMS GmbH, Hennigsdorf, Germany). Patients were divided into the following 2 groups according to the type of change of PCT: group 1, where PCT on day 3 was decreased by more than 30% or was below 0.25 ng/mL, and group 2, where PCT on day 3 was either increased above 0.25 ng/mL or decreased less than 30%. RESULTS: Death occurred in 12.3% of patients of group 1 and in 29.9% of those of group 2 (P < .0001). Odds ratio for death of patients of group 1 was 0.328. Odds ratio for the administration of inappropriate antimicrobials of patients of group 2 was 2.519 (P = .003). CONCLUSIONS: Changes of serum PCT within the first 48 hours reflect the benefit or not of the administered antimicrobial therapy. Serial PCT measurements should be used in clinical practice to guide administration of appropriate antimicrobials.

Salmonella enteritidis meningitis in a first time diagnosed AIDS patient: case report.

UNLABELLED: We describe a patient with salmonella enteritidis meningitis and unknown HIV infection. SETTING: A 14-bed adult intensive care unit in a tertiary hospital.The patient was brought to the emergency department with fever, nuchal rigidity and confusion. A first cerebrospinal fluid examination was non diagnostic. After a short period of improvement the patient developed septic shock. A second cerebrospinal fluid specimen was purulent. Both specimens yielded salmonella enteritidis and a blood culture as well. An Eliza reaction was performed and showed positive for HIV. The CD4(+) cells count was 16/mm3. The patient died with refractory shock eight days after admission in the intensive care unit.

Massive rupture of a hepatic hydatid cyst associated with mechanical ventilation.

UNLABELLED: An 80-yr-old woman with a complicated Echinococcus cyst of the liver underwent endotracheal intubation with a simple endotracheal tube and conventional mechanical ventilation that led to massive rupture of the cyst into the bronchi followed by fatal anaphylactic shock. We believe that the currently recommended use of a double-lumen endotracheal tube during surgery in the pulmonary hydatid cysts should be extended to hydatid cysts of the liver with thoracic involvement. IMPLICATIONS: We present a case of massive rupture of hepatic Echinococcus cyst associated with mechanical ventilation. We believe that the use of a double-lumen endotracheal tube could be crucial in the management of the hydatid cysts of the liver with thoracic involvement.