De-escalation therapy for severe sepsis and septic shock is a safe strategy associated with a lower mortality. Efforts to increase the frequency of this strategy are fully justified.

A potent synergy of a glycopeptide-colistin combination against Acinetobacter baumannii has recently been described. We set out to assess the efficacy and safety of this combination in a retrospective study including episodes of ventilator-associated pneumonia or bacteremia caused by carbapenem-resistant A. baumannii. We compared 29 patients (group I) treated with colistin plus vancomycin with 28 patients treated with colistin alone (group II). Group I received vancomycin (for empirical or targeted therapy) at the onset of colistin administration and both antimicrobials coincided for at least 5 days. Baseline characteristics, clinical cure, microbiological eradication, and mortality were similar in both groups but the rate of acute kidney injury was higher in group I (55.2 vs. 28%; p = 0.04). In critically ill patients with carbapenem-resistant A. baumannii infections, clinical outcomes do not differ in patients treated with colistin plus vancomycin from those receiving colistin without vancomycin. This combination significantly increases the risk of renal failure.

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have the capacity to produce vast amounts of interferon-alpha (IFN-α). In COVID-19 there is a deficit in DC numbers and IFNα production, which has been associated with disease severity. In this work, we described that in addition to the DC deficiency, several DC activation and homing markers were altered in acute COVID-19 patients, which were associated with multiple inflammatory markers. Remarkably, previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+ myeloid DCs and pDCs seven months after SARS-CoV-2 infection. Moreover, the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients, while no restoration of integrin β7 and indoleamine 2,3-dyoxigenase (IDO) levels were observed. These findings contribute to a better understanding of the immunological sequelae of COVID-19.

BackgroundThe increasing occurrence of multidrug resistant (MDR) bacteria arises at a time when there is a lack of antibiotics active against these pathogens and few new antimicrobials are in the pipelines of the pharmaceutical industry. Treatment of ventilator-associated pneumonia (VAP) caused especially by MDR Gram-negative bacilli (GNB) represents a real challenge due to the dearth of treatment options.MethodsWe searched the medical literature relevant about management of ventilator-associated pneumonia caused by multi-drug resistant pathogens including GNB and methicillin-resistant S. aureus.ResultsEmpirical therapy should be prescribed based on the local pattern of susceptibilities. Colistin and tigecycline are in many cases the unique options for the treatment of many episodes of VAP caused by MDR-GNB. Tigecyline (not licensed for treatment of pneumonia) should be used with an initial bolus of 200 mg followed by 100 mg every 12 h. The need for a loading dose and the administration of high doses of colistin (9 million IU/day in two or three doses) is currently accepted. Vancomycin has been considered the treatment of choice for pneumonia due to MRSA although linezolid may provide higher rate of clinical cure for MRSA VAP with a good safety profile. The initial antibiotic treatment must be reassessed and simplify in accordance of culture results.ConclusionsEmpirical treatment of VAP due to MDR pathogens should be based on knowledge of local ecology. A strategy combining early high doses of effective agents with subsequent simplification in the light of microbiologic information is recommended.

The aim was to assess the ability of nasopharyngeal SARS-CoV-2 viral load at first patient’s hospital evaluation to predict unfavorable outcomes. We conducted a prospective cohort study including 321 adult patients with confirmed COVID-19 through RT-PCR in nasopharyngeal swabs. Quantitative Synthetic SARS-CoV-2 RNA cycle threshold values were used to calculate the viral load in log10 copies/mL. Disease severity at the end of follow up was categorized into mild, moderate, and severe. Primary endpoint was a composite of intensive care unit (ICU) admission and/or death (n = 85, 26.4%). Univariable and multivariable logistic regression analyses were performed. Nasopharyngeal SARS-CoV-2 viral load over the second quartile (≥ 7.35 log10 copies/mL, p = 0.003) and second tertile (≥ 8.27 log10 copies/mL, p = 0.01) were associated to unfavorable outcome in the unadjusted logistic regression analysis. However, in the final multivariable analysis, viral load was not independently associated with an unfavorable outcome. Five predictors were independently associated with increased odds of ICU admission and/or death: age ≥ 70 years, SpO2, neutrophils > 7.5 × 103/µL, lactate dehydrogenase ≥ 300 U/L, and C-reactive protein ≥ 100 mg/L. In summary, nasopharyngeal SARS-CoV-2 viral load on admission is generally high in patients with COVID-19, regardless of illness severity, but it cannot be used as an independent predictor of unfavorable clinical outcome.