Infection-related ventilator-associated complications in ICU patients colonised with extended-spectrum β-lactamase-producing Enterobacteriaceae

Purpose

To investigate the clinical significance of infection-related ventilator-associated complications (IVAC) and their impact on carbapenem consumption in mechanically ventilated (MV) patients colonised with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBLE).

Methods

Inception cohort study from the French prospective multicenter OUTCOMEREA database (17 ICUs, 1997–2015) including all ESBLE carriers (systematic rectal swabbing at admission then weekly and/or urinary or superficial surgical site colonisation) with MV duration?>?48 h and?≥?1 episode of IVAC after carriage documentation. All ICU-acquired infections were microbiologically documented.

Results

The 318 enrolled ESBLE carriers (median age 68 years; males 67%; medical admission 68%; imported carriage 53%) experienced a total of 576 IVAC comprising 361 episodes (63%) without documented infection, 124 (21%) related to infections other than ventilator-associated pneumonia (VAP), 73 (13%) related to non-ESBLE VAP and 18 (3%) related to ESBLE VAP. Overall, ESBLE infections accounted for only 43 episodes (7%). Carbapenem exposure within the preceding 3 days was the sole independent predictor of ESBLE infection as the causative event of IVAC, with a protective effect (adjusted odds ratio 0.2, 95% confidence interval 0.05–0.6; P?<?0.01). Carbapenems were initiated in 9% of IVAC without infection, 15% of IVAC related to non-VAP infections, 42% of IVAC related to non-ESBLE VAP, and 56% of IVAC related to ESBLE VAP (ESBLE VAP versus non-ESBLE VAP: P?=?0.43).

Conclusions

IVAC in ESBLE carriers mostly reflect noninfectious events but act as a strong driver of empirical carbapenem consumption. ESBLE infections are scarce yet hard to predict, strengthening the need for novel diagnostic approaches and carbapenem-sparing alternatives.

     

Early PREdiction of sepsis using leukocyte surface biomarkers: the ExPRES-sepsis cohort study

Purpose

Reliable biomarkers for predicting subsequent sepsis among patients with suspected acute infection are lacking. In patients presenting to emergency departments (EDs) with suspected acute infection, we aimed to evaluate the reliability and discriminant ability of 47 leukocyte biomarkers as predictors of sepsis (Sequential Organ Failure Assessment score?≥?2 at 24 h and/or 72 h following ED presentation).

Methods

In a multi-centre cohort study in four EDs and intensive care units (ICUs), we standardised flow-cytometric leukocyte biomarker measurement and compared patients with suspected acute infection (cohort-1) with two comparator cohorts: ICU patients with established sepsis (cohort-2), and ED patients without infection or systemic inflammation but requiring hospitalization (cohort-3).

Results

Between January 2014 and February 2016, we recruited 272, 59 and 75 patients to cohorts 1, 2, and 3, respectively. Of 47 leukocyte biomarkers, 14 were non-reliable, and 17 did not discriminate between the three cohorts. Discriminant analyses for predicting sepsis within cohort-1 were undertaken for eight neutrophil (cluster of differentiation antigens (CD) CD15; CD24; CD35; CD64; CD312; CD11b; CD274; CD279), seven monocyte (CD35; CD64; CD312; CD11b; HLA-DR; CD274; CD279) and a CD8 T-lymphocyte biomarker (CD279). Individually, only higher neutrophil CD279 [OR 1.78 (95% CI 1.23–2.57); P?=?0.002], higher monocyte CD279 [1.32 (1.03–1.70); P?=?0.03], and lower monocyte HLA-DR [0.73 (0.55–0.97); P?=?0.03] expression were associated with subsequent sepsis. With logistic regression the optimum biomarker combination was increased neutrophil CD24 and neutrophil CD279, and reduced monocyte HLA-DR expression, but no combination had clinically relevant predictive validity.

Conclusions

From a large panel of leukocyte biomarkers, immunosuppression biomarkers were associated with subsequent sepsis in ED patients with suspected acute infection.

Clinical trial registration

NCT02188992.

     

Safety and tolerability of a single administration of AR-301, a human monoclonal antibody,in ICU patients with severe pneumonia caused by <Emphasis Type="Italic">Staphylococcus aureus</Emphasis>: first-in-human trial

Purpose

Hospital-acquired bacterial pneumonia (HABP) is a critical concern in hospitals with ventilator-associated bacterial pneumonia (VABP) remaining the most common infection in the ICU, often due to Staphylococcus aureus, an increasingly difficult to treat pathogen. Anti-infective monoclonal antibodies (mAb) may provide new, promising treatment options. This randomized, double-blinded, placebo-controlled study aimed at assessing the safety and pharmacokinetics of AR-301, an S. aureus alpha toxin-neutralizing mAb, and exploring its clinical and microbiologic outcomes when used adjunctively with standard-of-care antibiotics.

Methods

Eligibility in this trial required microbiologically confirmed severe S. aureus pneumonia, including HABP, VABP or CABP, treated in the ICU and an APACHE II score ≤?30. Standard-of-care antibiotics selected by the investigators were administered to all patients in the study following clinical and microbiologic confirmation of S. aureus pneumonia. Adjunctive treatment of AR-301 was to start <?36 h after onset of severe pneumonia. AR-301 was administered to four sequentially ascending dose cohorts. The placebo cohort received antibiotics and a placebo buffer. Clinical outcomes were adjudicated by a blinded committee. S. aureus eradication was declared based on a negative follow-up culture and presumed to be negative when no culture was obtained in the presence of clinical improvement.

Results

Thirteen ICUs enrolled 48 patients, with pneumonia attributable to MRSA in six subjects. The study drug displayed a favorable safety profile: Of 343 AEs reported, 8 (2.3%) were deemed related, none serious. In a post hoc subgroup analysis of VABP patients receiving AR-301, ventilation duration was shorter for AR-301-treated patients compared with the placebo group. Overall, there was a trend toward a better and faster microbiologic eradication at day 28. The PK profile of AR-301 is consistent with that of a human IgG1 mAb, with a plasma half-life of about 25 days.

Conclusions

Adjunctive treatment of severe S. aureus HABP with anti-staphylococcal mAbs appears feasible and suggests some clinical benefits, but larger randomized studies are needed to better define its safety and efficacy.

     

Clinical spectrum and short-term outcome of adult patients with purpura fulminans: a French multicenter retrospective cohort study

Purpose

Data on purpura fulminans (PF) in adult patients are scarce and mainly limited to meningococcal infections. Our aim has been to report the clinical features and outcomes of adult patients admitted in the intensive care unit (ICU) for an infectious PF, as well as the predictive factors for limb amputation and mortality.

Methods

A 17-year national multicenter retrospective cohort study in 55 ICUs in France from 2000 to 2016, including adult patients admitted for an infectious PF defined by a sudden and extensive purpura, together with the need for vasopressor support. Primary outcome variables included hospital mortality and amputation during the follow-up period (time between ICU admission and amputation, death or end of follow-up).

Results

Among the 306 included patients, 126 (41.2%; 95% CI 35.6–46.9) died and 180 (58.8%; 95% CI 53.3–64.3) survived during the follow-up period [13 (3–24) days], including 51/180 patients (28.3%, 95% CI 21.9–35.5) who eventually required limb amputations, with a median number of 3 (1–4) limbs amputated. The two predominantly identified microorganisms were Neisseria meningitidis (63.7%) and Streptococcus pneumoniae (21.9%). By multivariable Cox model, SAPS II [hazard-ratio (HR)?=?1.03 (1.02–1.04); p?<?0.001], lower leucocytes [HR 0.83 (0.69–0.99); p?=?0.034] and platelet counts [HR 0.77 (0.60–0.91); p?=?0.007], and arterial blood lactate levels [HR 2.71 (1.68–4.38); p?<?0.001] were independently associated with hospital death, while a neck stiffness [HR?0.51 (0.28–0.92); p?=?0.026] was a protective factor. Infection with Streptococcus pneumoniae [sub-hazard ratio 1.89 (1.06–3.38); p?=?0.032], together with arterial lactate levels and ICU admission temperature, was independently associated with amputation by a competing risks analysis.

Conclusion

Purpura fulminans carries a high mortality and morbidity. Pneumococcal PF leads to a higher risk of amputation.

Trials registration

NCT03216577.

     

Mortality outcomes based on ED qSOFA score and HIV status in a developing low income country

Objective

To evaluate the utility of the quick Sepsis-related Organ Failure Assessment (qSOFA) score to predict risks for emergency department (ED) and hospital mortality among patients in a sub-Saharan Africa (SSA) setting.

Rehabilitation after total joint replacement: a scoping study

Purpose: The evidence supporting rehabilitation after joint replacement, while vast, is of variable quality making it difficult for clinicians to apply the best evidence to their practice. We aimed to map key issues for rehabilitation following joint replacement, highlighting potential avenues for new research.

Materials and methods: We conducted a scoping study including research published between January 2013 and December 2016, evaluating effectiveness of rehabilitation following hip and knee total joint replacement. We reviewed this work in the context of outcomes described from previously published research.

Results: Thirty individual studies and seven systematic reviews were included, with most research examining the effectiveness of physiotherapy-based exercise rehabilitation after total knee replacement using randomized control trial methods. Rehabilitation after hip and knee replacement whether carried out at the clinic or monitored at home, appears beneficial but type, intensity and duration of interventions were not consistently associated with outcomes. The burden of comorbidities rather than specific rehabilitation approach may better predict rehabilitation outcome. Monitoring of recovery and therapeutic attention appear important but little is known about optimal levels and methods required to maximize outcomes.

Conclusions: More work exploring the role of comorbidities and key components of therapeutic attention and the therapy relationship, using a wider range of study methods may help to advance the field.

• Implications for Rehabilitation

• Physiotherapy-based exercise rehabilitation after total hip replacement and total knee replacement, whether carried out at the clinic or monitored at home, appears beneficial.

• Type, intensity, and duration of interventions do not appear consistently associated with outcomes.

• Monitoring a patient’s recovery appears to be an important component. The available research provides limited guidance regarding optimal levels of monitoring needed to achieve gains following hip and knee replacement and more work is required to clarify these aspects.

• The burden of comorbidities appears to better predict outcomes regardless of rehabilitation approach.