key: cord-1027041-1qov44yq
authors: Lardaro, Thomas; Wang, Alfred Z.; Bucca, Antonino; Croft, Alexander; Glober, Nancy; Holt, Daniel B.; Musey, Paul I.; Peterson, Kelli D.; Trigonis, Russell A.; Schaffer, Jason T.; Hunter, Benton R.
title: Characteristics of COVID‐19 patients with bacterial coinfection admitted to the hospital from the emergency department in a large regional healthcare system
date: 2021-02-12
journal: J Med Virol
DOI: 10.1002/jmv.26795
sha: 86d0b4cea7568347970d9fde9a0e5c5bf2c5d45b
doc_id: 1027041
cord_uid: 1qov44yq

INTRODUCTION: The rate of bacterial coinfection with SARS‐CoV‐2 is poorly defined. The decision to administer antibiotics early in the course of SARS‐CoV‐2 infection depends on the likelihood of bacterial coinfection. METHODS: We performed a retrospective chart review of all patients admitted through the emergency department with confirmed SARS‐CoV‐2 infection over a 6‐week period in a large healthcare system in the United States. Blood and respiratory culture results were abstracted and adjudicated by multiple authors. The primary outcome was the rate of bacteremia. We secondarily looked to define clinical or laboratory features associated with bacteremia. RESULTS: There were 542 patients admitted with confirmed SARS‐CoV‐2 infection, with an average age of 62.8 years. Of these, 395 had blood cultures performed upon admission, with six true positive results (1.1% of the total population). An additional 14 patients had positive respiratory cultures treated as true pathogens in the first 72 h. Low blood pressure and elevated white blood cell count, neutrophil count, blood urea nitrogen, and lactate were statistically significantly associated with bacteremia. Clinical outcomes were not statistically significantly different between patients with and without bacteremia. CONCLUSIONS: We found a low rate of bacteremia in patients admitted with confirmed SARS‐CoV‐2 infection. In hemodynamically stable patients, routine antibiotics may not be warranted in this population.

of these recommendations are based on limited evidence due to the novelty of the disease.

One clinical dilemma raised by the SSC is whether to use antibiotics in patients with COVID-19. Discerning concomitant bacterial sepsis or superinfection among patients with COVID-19 can be very difficult, given the similarity in symptoms (fever, cough, myalgias, etc.). 4 The uncertainty surrounding clinical management is reflected in data from Wuhan, where up to 53% of patients with the nonsevere disease and >90% of patients admitted to the hospital were given intravenous antibiotics. [5] [6] [7] A systematic review of 76 studies encompassing over 11,000 patients with COVID-19 found that 64% were treated with antibiotic Data from other severe respiratory viruses suggest significant rates of bacterial co-infection. Research on the Middle East Respiratory Syndrome demonstrated an 18% bacterial coinfection rate in 330 patients in the ICU, 8 while the reported bacterial coinfection rate in influenza ranges from 11% to 35%. 9 Recent systematic reviews have reported bacterial coinfection rates of approximately 7% for hospitalized patients with COVID-19, but are based on a small number of studies, many of which do not discern between bacterial infections present on admission versus those acquired in the hospital. 10, 11 A large multicenter registry reported a 3.5% community-onset bacterial coinfection with COVID- 19, 12 and despite the frequent use of broad-spectrum antibiotics, further data is urgently needed. 13 Further, patients with suspected bacterial coinfection may have worse outcomes. 14 The most current guidelines from the SSC recommend empiric antimicrobial treatment for mechanically ventilated patients, with early de-escalation guided by microbiology and culture results, but acknowledge those recommendations are based on low-quality evidence. 3 This study aimed to define the rate of bacteremia or bacterial coinfection in admitted COVID-19 patients and to identify clinical or laboratory risk factors associated with bacteremia to help guide early antimicrobial use.

This retrospective chart review was approved as exempt research by the local institutional review board.

The study took place across a large integrated health system that includes 14 hospitals across the state of Indiana. Annual emergency department (ED) volume across the hospitals ranges from approximately 6000 to 90,000, and the system sees over 400,000 combined ED patients annually.

Included patients were adults aged ≥18 years, admitted to the hospital from the ED between March 1, 2020, and April 13, 2020, with a positive polymerase chain reaction (PCR) test for SARS-CoV-2 within 3 days of admission. Patients with a PCR test obtained greater than 3 days after hospital admission were excluded because this is the earliest timeframe in which a positive test could be reasonably attributed to an infection occurring during the early part of the hospitalization, rather than being present before admission. No further exclusion criteria were applied.

Data were abstracted using a standardized form and were entered into REDCap, 15 a secure data collection instrument. Extracted data included days from symptom onset to ED presentation, basic demographics (age and gender), comorbidities, ED vitals signs, laboratory values (culture results and chest imaging results), and level of care at the time of admission. The level of care was defined based on the computerized order entered by the admitting hospitalist team.

Chest imaging results based on final radiologist interpretation were labeled as "clear," "single lobe infiltrates," "multilobar infiltrates," or "clear x-ray with involvement on CT only." Vital signs included initial and final ED blood pressure, heart rate, oxygen saturation, temperature, and respiratory rate. If an ambulatory oxygen saturation was documented in the electronic medical record (EMR), it was extracted and recorded separately. Comorbidities were based on chart review of the ED note, admission note, and any clinic or primary care notes available in the EMR. The presence or absence of the following comorbidities was recorded for each patient: smoking, obesity, hypertension, diabetes, hyperlipidemia, heart failure, previous ischemic heart disease, active cancer, dialysis-dependent renal disease, chronic obstructive pulmonary disease (COPD), asthma, active cancer, current chemotherapy, HIV, history of organ transplantation, and current use of oral immunosuppressants.

The primary outcome was the rate of true positive blood cultures performed at admission (within 24 h of hospital arrival) in patients who tested positive for COVID-19. All blood culture results were initially documented as negative, positive (any bacterial growth in any bottle), or not done. Since some positive blood cultures can be caused by skin contaminants not causing any infection, all positive cultures were adjudicated by two authors as either true positive or contaminants. Criteria to determine "true positive" versus "contaminant" were predefined. Institutional protocol directs the collection of four bottles (two from each of two different sites) when drawing blood cultures. Any case in which more than two of four bottles grew bacteria were considered true positives. Any patient with repeat blood cultures that were positive was considered true positive. The growth of bacteria outside of typical skin flora (such as staphylococcus or streptococcus) was generally considered true positive. If a positive in <3 of four bottles was noted to be a "probable contaminant" in the provider notes or infectious disease consultation notes, and if antibiotics were discontinued before 5 days of treatment, growth was classified as a false positive. In cases of disagreement, the discrepancy was resolved through discussion or adjudicated by a third author. Patients in whom no blood cultures were drawn within 72 h were classified as not bacteremic. Patients with positive culture results were thus divided into "true positive" bacteremia versus "contaminant." We defined associations between clinical variables and true positive blood cultures and compared clinical outcomes between those with and without true positive blood cultures.

We also assessed respiratory cultures drawn in the first 72 h.

Since it is more difficult to define a true positive respiratory culture versus contaminant or carrier state, all respiratory cultures with bacterial growth were considered true pathogens if the admitting team treated them as such, and incidental (not causing the infection) if the care team noted the findings to be likely noninfectious and the patient was successfully treated without antibiotics.

Urine cultures were not included in our analyses, since urinalysis can be performed with immediate results to guide antibiotic treatment related to urine infections, so initially "occult" urine infection is unlikely. Further, asymptomatic bacteriuria is common in some populations.

Mean ages were compared using a two-sided t test after a test for the ratio between the two standard deviations showed no significant 

We identified 542 adults with a positive COVID-19 PCR test admitted during the study period, and all were included. Table 1 Table 3 displays the initial vital sign, laboratory, and radiographic data stratified by the presence or absence of early bacteremia.

Although patients with bacteremia tended to have higher heart rate, higher respiratory rate, and lower oxygen saturation, the only vital sign differences reaching statistical significance were systolic and diastolic blood pressures, which were both lower in patients with bacteremia. Patients with bacteremia had significantly higher white blood cell counts (13.5 vs. 7.3), neutrophil counts (12.4 vs. 5.7), and lactate (4.1 vs. 1.6). C-reactive protein and procalcitonin values were higher in patients with bacteremia but these differences did not reach statistical significance. Table 4 displays vital sign, laboratory, and radiology findings among the 20 patients with any true positive bacterial culture (blood or respiratory) compared to those without any true positive bacterial culture. Vital sign findings were similar to the comparisons in Table 3, with lower blood pressure noted in patients with bacterial co- Additionally, the current study adds to previous work to determine the rate of bacterial coinfection in patients with COVID-19.

Recent systematic reviews have found bacterial co-infection rates with COVID-19 of 6.9% and 7.0% overall. 10, 11 One review noted that the rate of co-infection at presentation was 3.5%, with the remainder attributed to hospital-acquired infections. 10 We prioritized bacteremia as our primary outcome because of the difficulty in defining a true positive respiratory culture. We found that an additional 2.6% of patients were treated for a bacterial pulmonary pathogen identified within the first 72 h of admission.

While these patients were treated with antibiotics at our institution, it is unclear whether these cultures represented true bacterial pathogens or incidental bacterial flora.

We found a very small number of bacteremic patients. The small number of true positives also limited our ability to find statistical associations between patient characteristics and bacteremia, and there were far too few cases to try to derive a decision instrument.

Although we set objective criteria for true positive cultures versus contaminants, there is no universally accepted way to adjudicate such cases, and this process may lead to errors resulting in either over-or underestimation of bacterial infections.

Seasonal variations in bacterial sepsis and influenza may also impact the applicability of these results to different times of the year.

Lastly, although the data was taken from 14 different hospitals, they all operate in the same state under the same healthcare system, so our results may not be widely applicable to other healthcare systems or settings.

We found a low rate of bacteremia or bacterial pulmonary infection among patients admitted to the hospital with confirmed COVID-19

infection. Combined with other studies, our results suggest that physicians may consider treating hemodynamically stable patients with confirmed COVID-19 and without high clinical suspicion for bacterial coinfection without routine antibiotics.

The authors declare that there are no conflict of interests. 

The data that support the findings of this study are available upon reasonable request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

The peer review history for this article is available at https://publons. 

Organization WH WHO Coronavirus Disease (COVID-19) Dashboard

Management of critically ill adults with COVID-19

Surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19)

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Clinical characteristics of coronavirus disease 2019 in China

Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China

Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a singlecentered, retrospective, observational study. The Lancet

Critically Ill patients with the middle east respiratory syndrome: a multicenter retrospective cohort study

The frequency of influenza and bacterial coinfection: a systematic review and meta-analysis. Influenza Other Respir Viruses

Bacterial co-infection and secondary infection in patients with COVID-19: a living rapid review and meta-analysis

Co-infections in people with COVID-19: a systematic review and meta-analysis

Empiric antibacterial therapy and community-onset bacterial co-infection in patients hospitalized with covid-19: a multi-hospital cohort study

Bacterial and fungal coinfection in individuals with coronavirus: a rapid review to support COVID-19 antimicrobial prescribing

Clinical characteristics and antibiotics treatment in suspected bacterial infection patients with COVID-19

Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support

Exchange NIfHaC. Coronavirus (COVID-19)

Clinical presentations, laboratory and radiological findings, and treatments for 11,028 COVID-19 patients: a systematic review and meta-analysis

Procalcitonin testing to guide antibiotic therapy for the treatment of sepsis in intensive care settings and for suspected bacterial infection in emergency department settings: a systematic review and cost-effectiveness analysis

Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis

Laboratory findings in SARS-CoV-2 infections: state of the art

Characteristics of COVID-19 patients with bacterial coinfection admitted to the hospital from the emergency department in a large regional healthcare system