Prophylactic Antibiotic May Reduce VAP After Cardiac Arrest
A 2-day course of prophylactic antibiotic therapy can lower the risk of early ventilator-associated pneumonia (VAP) in cardiac arrest patients, a new study suggests.
Investigators compared administration of amoxicillin-clavulanate vs placebo in adult patients on mechanical ventilation following out-of-hospital cardiac arrest and treated with targeted temperature management.
Although fewer patients in the antibiotic group experienced early VAP than in the placebo group, there were no other significant differences in outcomes such as the incidence of late VAP or length of intensive care unit (ICU) stay.
“All out-of-hospital cardiac arrest patients receiving mild therapeutic hypothermia should receive routine VAP prevention with a 2-day course of amoxicillin-clavulanate in order to reduce VAP incidence and fight against antimicrobial resistance through antibiotic consumption reduction,” lead author Bruno Francois, MD, a critical care physician, intensive care unit and inserm clinical investigation centers, Hospital of Limoges, France, told theheart.org | Medscape Cardiology.
The study was published online November 7 in the New England Journal of Medicine.
Targeted temperature management is recommended in patients with out-of-hospital cardiac arrest with initial shockable rhythm but is associated with increased risk of secondary infections and is also an independent risk factor for early VAP, the authors write.
Previous research suggested a decreased incidence of infectious complications when antibiotic therapy was administered to patients receiving targeted temperature management following cardiac arrest.
Taking into consideration the most frequently isolated bacteria in early VAP in this population, treatment duration used in previous studies, and to avoid potential antibiotic resistance associated with prolonged antibiotic therapy, the researchers chose intravenous amoxicillin-clavulanate used over a 2-day period in the Antibiotherapy During Therapeutic Hypothermia to Prevent Infectious Complications (ANTHARTIC) trial.
The analysis, which was conducted in 16 ICUs in France, included 194 adult patients (aged ≥ 18 years; median age, 61 years [interquartile range, 50 – 73]; 80% male) who were hospitalized following out-of-hospital cardiac arrest with shockable rhythm and treated with 32° C to 34° C (89.6° F to 93.2° F) targeted temperature management.
Patients were randomly assigned to receive a 2-day course of either antibiotic therapy or placebo (99 vs 95 patients, respectively).
The antibiotic, amoxicillin-clavulanate (1 g and 200 mg, respectively), was initiated less than 6 hours after the cardiac arrest.
“Early VAP” was defined as VAP that occurred during the first 7 days of hospitalization.
In total, the investigators reported 80 cases of VAP; however, after review by an adjudication committee, it was found that there were a total of 52 cases of early VAP and nine cases of late VAP.
The incidence of early VAP was lower in the antibiotic group, compared with the placebo group (cumulative incidence on day 7, 19% vs 34%; hazard ratio, 0.53; 95% confidence interval, 0.31 – 0.92; P = .03).
On the other hand, the occurrence of late VAP was similar in the two groups (4/99 vs 5/95 patients, respectively).
When the researchers used a 5-day cutoff value to differentiate between “early” and “late” VAP, they obtained similar results.
No significant differences were found between the antibiotic group and the placebo group in the other outcomes:
Late VAP: 4% vs 5%
Number of ventilator-free days: 21 vs 19
ICU length of stay: 5 days vs 8 days in patients who were discharged
ICU length of stay: 7% for both groups in patients who died
Mortality at day 28: 41% vs 37%
No antibiotic resistance was detected at day 7, and there were no significant differences in adverse events between the two groups.
The authors suggest that the reason the incidence of late VAP was unaffected by the antibiotic intervention is that late VAP “is mostly driven by prolonged mechanical ventilation with a distinct microbiologic epidemiology.”
They also point to several limitations in their research, including the concerns that patients with overt aspiration were not included in the trial and that the microbiota analysis was designed to detect only multidrug-resistant bacteria and also was not repeated after day 7.
It “remains to be determined” if the same results apply to patients with out-of-hospital cardiac arrest receiving a different targeted temperature, the authors state.
“VAP incidence remains pretty high in cardiac arrest patients and may negatively impact outcome, which is already poor because of neurological sequelae,” Francois said.
“Therefore any preventive method should be investigated to reduce this type of nosocomial event,” he emphasized.
Safe and Cost-Effective
Commenting on the study for told theheart.org | Medscape Cardiology, Jordi Rello MD, PhD, professor of medicine, Universitat Autònoma de Barcelona, Spain, said that the study’s main contribution is “that [a] single, nonexpensive intervention was effective to reduce VAP rates.”
Rello, who is also the director of the Clinical Research & Innovation in Pneumonia and Sepsis (CRIPS) Group at Vall d’Hebron Research Institute and was not involved with the study, stated the take-home message is that “pulmonary infections are very prevalent after cardiac arrest and can be prevented by a short course of antibiotics without ecological adverse events.”
Francois added that the “preventive intervention is safe and cost-effective.”
The study was funded by the French Ministry of Health. Francois reported that his institution received grants from the French Ministry of Health. The other authors’ disclosures are listed online. Rello has disclosed no relevant financial relationships.
N Engl J Med. Published online November 7, 2019. Abstract