Empiric antibiotic use confers no therapeutic benefit in COVID-19 pneumonia

The use of empiric antibiotic therapy appears to prevent neither deterioration nor death among patients with COVID-19 pneumonia, as shown in a Singapore study.

In a group of patients with COVID-19 pneumonia, antibiotics were commonly started in those who were severely ill. Patients who did vs did not receive antibiotics more often developed diarrhoea (34.7 percent vs 11.8 percent; p<0.01) and had slightly higher subsequent admissions to the intensive care unit (ICU; 8.0 percent vs 4.9 percent; p=0.384). [Antibiotics 2022;doi:10.3390/antibiotics11020184]

Furthermore, antibiotic treatment did not result in lower 30-day (adjusted odds ratio [aOR], 19.528, 95 percent confidence interval [CI], 1.039–367.021) or in-hospital mortality (aOR 3.870, 95 percent CI, 0.433–34.625) rates in an analysis that controlled for age, comorbidities, and severity of COVID-19 illness.

The best performing inflammatory marker for predicting bacterial infections was the C-reactive protein (CRP) level (area under the curve, 0.822) although the sensitivity and specificity were <90 percent.

When COVID-19 intersects with other respiratory viruses

“COVID-19 imposes challenges in antibiotic decision-making due to similarities between bacterial pneumonia and moderate to severe COVID-19,” according to the investigators.

The typical symptoms of COVID-19 pneumonia, such as fever, cough and dyspnoea, often prompt clinicians to start empiric antibiotic treatment while waiting for diagnostic testing such as a SARS-CoV-2 polymerase chain reaction test, radiology, and blood investigations.

The investigators also noted that even if COVID-19 is confirmed, it is common that empiric antibiotics are continued pending further evaluation if the treating physician is not able to conclude that bacterial co-infections have been adequately excluded.

“It is understandable that healthcare providers would err on the side of antibiotic treatment, especially in the hospitalized and the critically ill. However, it is important to be reminded that antibiotics are not without side effects,” they pointed out.

Indeed, the patients treated with antibiotics in the current study were more likely to have diarrhoea. What is more is the concern that widespread unnecessary antibiotic use will subject patients to the risks of adverse effects and worsening of antimicrobial resistance globally. [Lancet Glob Health 2020;8:e1453-e1454]

“Evaluating the use of antibiotics in COVID-19 pneumonia patients will be an important step to mitigate drug toxicities and antimicrobial resistance. International guidelines recommend that cultures be obtained prior to antibiotics and that therapy be accessed daily for de-escalation,” according to the investigators. “When microbiology cultures are negative, antibiotics should be discontinued.” [Clin Microbiol Infect 2021;27:61-66; www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1; www.covid19treatmentguidelines.nih.gov/]

Study details

The total study population included 717 patients (median age 46 years, 42.8 percent female, 55.9 percent Chinese) hospitalized with COVID-19 at the National Centre for Infectious Diseases and Tan Tock Seng Hospital, Singapore, from January to April 2020. Of these, 86 (12.0 percent) were treated with antibiotics and 26 (3.6 percent) had documented bacterial infections.

Of the 278 patients with COVID-19 pneumonia, 86 (12.0 percent) were treated with antibiotics and only 54 (7.5 percent) had documented suspected or confirmed bacterial infections. Among patients without pneumonia, only 11 (2.5 percent) received antibiotics.

Patients treated with antibiotics were more likely to be older (60 vs 55 years; p=0.008), have higher peak CRP levels (122.5 vs 37.5 mg/L; p=0.008), be admitted to the ICU at the time of COVID-19 pneumonia diagnosis (34.7 percent vs 3.0 percent; p<0.001), and have received mechanical ventilation (17.3 percent vs 0.5 percent; p<0.001). The majority of the patients were treated with an “access” group of antibiotics (eg, amoxicillin–clavulanate), as recommended by the World Health Organization guidelines.

The investigators called for additional studies on procalcitonin and CRP levels to evaluate their utility in antibiotic decision-making in COVID-19 pneumonia.