Rapid evolution and host immunity drive the rise and fall of carbapenem resistance during an acute Pseudomonas aeruginosa infection.

It is well established that antibiotic treatment selects for resistance, but the dynamics of this process during infections are poorly understood. Here we map the responses of Pseudomonas aeruginosa to treatment in high definition during a lung infection of a single ICU patient. Host immunity and antibiotic therapy with meropenem suppressed P. aeruginosa, but a second wave of infection emerged due to the growth of oprD and wbpM meropenem resistant mutants that evolved in situ. Selection then led to a loss of resistance by decreasing the prevalence of low fitness oprD mutants, increasing the frequency of high fitness mutants lacking the MexAB-OprM efflux pump, and decreasing the copy number of a multidrug resistance plasmid. Ultimately, host immunity suppressed wbpM mutants with high meropenem resistance and fitness. Our study highlights how natural selection and host immunity interact to drive both the rapid rise, and fall, of resistance during infection.

Pandemic and post-pandemic influenza A (H1N1) infection in critically ill patients.

BACKGROUND: There is a vast amount of information published regarding the impact of 2009 pandemic Influenza A (pH1N1) virus infection. However, a comparison of risk factors and outcome during the 2010-2011 post-pandemic period has not been described. METHODS: A prospective, observational, multi-center study was carried out to evaluate the clinical characteristics and demographics of patients with positive RT-PCR for H1N1 admitted to 148 Spanish intensive care units (ICUs). Data were obtained from the 2009 pandemic and compared to the 2010-2011 post-pandemic period. RESULTS: Nine hundred and ninety-seven patients with confirmed An/H1N1 infection were included. Six hundred and forty-eight patients affected by 2009 (pH1N1) virus infection and 349 patients affected by the post-pandemic Influenza (H1N1)v infection period were analyzed. Patients during the post-pandemic period were older, had more chronic comorbid conditions and presented with higher severity scores (Acute Physiology And Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA)) on ICU admission. Patients from the post-pandemic Influenza (H1N1)v infection period received empiric antiviral treatment less frequently and with delayed administration. Mortality was significantly higher in the post-pandemic period. Multivariate analysis confirmed that haematological disease, invasive mechanical ventilation and continuous renal replacement therapy were factors independently associated with worse outcome in the two periods. HIV was the only new variable independently associated with higher ICU mortality during the post-pandemic Influenza (H1N1)v infection period. CONCLUSION: Patients from the post-pandemic Influenza (H1N1)v infection period had an unexpectedly higher mortality rate and showed a trend towards affecting a more vulnerable population, in keeping with more typical seasonal viral infection.

Severe 2009 A/H1N1v influenza in pregnant women in Spain.

OBJECTIVES: To describe the severity of the 2009 influenza A/H1N1v illness among pregnant women admitted to Spanish intensive care units. DESIGN AND PATIENTS: Prospective, observational, multicenter study conducted in 148 Spanish intensive care units. We reviewed demographic and clinical data from the Spanish Society of Intensive Care Medicine database reported from April 23, 2009, to February 15, 2010. We included women of reproductive age (15-44 yrs) with confirmed A/H1N1v infection admitted to intensive care units. MAIN RESULTS: Two hundred thirty-four women of reproductive age were admitted to intensive care units, 50 (21.4%) of them pregnant. Seven deaths were recorded in pregnant and 22 in nonpregnant women. Among intensive care unit admissions, there were no statistically significant differences between pregnant women and nonpregnant in Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment scores, chest x-rays, inotrope requirement, or need for mechanical ventilation or steroid therapy. Mortality risk was significantly associated with Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment, and obesity. Viral pneumonia was more frequent in pregnant women than in nonpregnant women, with an odds ratio (adjusted for asthma, time from onset influenza symptoms to hospital admission and obesity) of 4.9 (95% confidence interval: 1.4-17.2). The development of primary viral pneumonia in women of reproductive age appeared to be related to the time of commencement of antiviral treatment, the lowest rates being reported with initiation of antiviral therapy within 48 hrs of symptom onset (63.6% vs. 82.6%, p = .03). However, antiviral therapy was started within this time span in only 14% of pregnant women. CONCLUSIONS: More than 20% of women of reproductive age admitted to intensive care unit for pH1N1 infection were pregnant. Pregnancy was significantly associated with primary viral pneumonia. Pregnant women should receive prompt treatment with oseltamivir within 48 hrs of the onset of influenza symptoms.

Impact of obesity in patients infected with 2009 influenza A(H1N1).

OBJECTIVE: A large proportion of patients infected with 2009 influenza A(H1N1) (A[H1N1]) are obese. Obesity has been proposed as a risk factor influencing outcome in these patients. However, its role remains unclear. We evaluate the outcome of patients who are obese and infected with A(H1N1) in the ICU, determining whether obesity is a risk factor for mortality. METHODS: This was a prospective, observational, and multicenter study performed in 144 ICUs in Spain. Data were obtained from the Grupo de Trabajo en Enfermedades Infecciosas de la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (GTEI/SEMICYUC) registry. Adult patients with A(H1N1) that was confirmed by real-time polymerase chain reaction were included in the analysis. Patients who were obese (BMI > 30) were compared with patients who were nonobese. Cox regression analysis was used to determine adjusted mortality. Differences of P < .05 were considered significant. RESULTS: In January 2010, the GTEI/SEMICYUC registry had complete records for 416 patients. One hundred and fifty patients (36.1%) were obese, of whom 67 (44.7%) were morbidly obese (BMI > 40). Mechanical ventilation (MV) was more frequently applied in patients who were obese (64% vs 52.4%, P < .01) Patients with obesity remained on MV longer than patients who were nonobese (6.5 ± 10.3 days vs 9.3 ± 9.7 days, P = .02), had longer ICU length of stay (10.8 ± 12.1 days vs 13.7 ± 11.7 days, P = .03), and had longer hospitalization (18.2 ± 14.6 days vs 22.2 ± 16.5 days, P = .02). Mortality adjusted by severity and potential confounders identified that obesity was not significantly associated with ICU mortality (hazard ratio, 1.1; 95% CI, 0.69-1.75; P = .68). CONCLUSIONS: In our cohort, patients who were obese and infected with A(H1N1) did not have increased mortality. However, there was an association between obesity and higher ICU resource consumption.

Effectiveness of treatments for severe sepsis: a prospective, multicenter, observational study.

RATIONALE: Several Surviving Sepsis Campaign Guidelines recommendations are reevaluated. OBJECTIVES: To analyze the effectiveness of treatments recommended in the sepsis guidelines. METHODS: In a prospective observational study, we studied all adult patients with severe sepsis from 77 intensive care units. We recorded compliance with four therapeutic goals (central venous pressure 8 mm Hg or greater for persistent hypotension despite fluid resuscitation and/or lactate greater than 36 mg/dl, central venous oxygen saturation 70% or greater for persistent hypotension despite fluid resuscitation and/or lactate greater than 36 mg/dl, blood glucose greater than or equal to the lower limit of normal but less than 150 mg/dl, and inspiratory plateau pressure less than 30 cm H(2)O for mechanically ventilated patients) and four treatments (early broad-spectrum antibiotics, fluid challenge in the event of hypotension and/or lactate greater than 36 mg/dl, low-dose steroids for septic shock, drotrecogin alfa [activated] for multiorgan failure). The primary outcome measure was hospital mortality. The effectiveness of each treatment was estimated using propensity scores. MEASUREMENTS AND MAIN RESULTS: Of 2,796 patients, 41.6% died before hospital discharge. Treatments associated with lower hospital mortality were early broad-spectrum antibiotic treatment (treatment within 1 hour vs. no treatment within first 6 hours of diagnosis; odds ratio, 0.67; 95% confidence interval, 0.50-0.90; P = 0.008) and drotrecogin alfa (activated) (odds ratio, 0.59; 95% confidence interval, 0.41-0.84; P = 0.004). Fluid challenge and low-dose steroids showed no benefits. CONCLUSIONS: In severe sepsis, early administration of broad-spectrum antibiotics in all patients and administration of drotrecogin alfa (activated) in the most severe patients reduce mortality.