Key clinical pearls in the medical management of hospitalized patients with coronavirus (Covid-19) infection

First, a shout-out to dedicated healthcare workers everywhere who have selflessly given of themselves to care for the sick during this pandemic. Thank you! Together, I know we will get through it!

Although our understanding of Covid-19 infection is far from complete, in the spirit of clarity and brevity of my posts on Pearls4Peers, here are some key points I have gleaned from review of existing literature and the CDC that may be useful as we care for our hospitalized patients with suspected or confirmed Covid-19 infection.

  • Isolation precautions.1 Per CDC, follow a combination of airborne (particularly when aerosol generating procedures is anticipated, including nebulizer treatment) and contact precaution protocols. Routinely use masks or respirators, such as N-95s (subject to local availability and policy) and eye protection. Don gowns (subject to local availability and policy) and gloves and adhere to strict hand hygiene practices.

 

  • Diagnostic tests1-9
    • Laboratory tests. Routine admission labs include CBC, electrolytes, coagulation panels and liver and renal tests. Other frequently reported labs include LDH, C-reactive protein (CRP) and procalcitonin. Testing for high sensitivity troponin I has also been performed in some patients, presumably due to concern over ischemic cardiac injury or myocarditis.2 Check other labs as clinically indicated.
    • Chest radiograph/CT chest. One or both have been obtained in virtually all reported cases with CT having higher sensitivity for detection of lung abnormalities.
    • EKG. Frequency of checking EKGs not reported in many published reports thought 1 study reported “acute cardiac injury” in some patients, based in part on EKG findings.4 Suspect we will be checking EKGs in many patients, particularly those who are older or are at risk of heart disease.
    • Point-of-care ultrasound (POCUS). This relatively new technology appears promising in Covid-19 infections, including in rapid assessment of the severity of pneumonia or ARDS at presentation and tracking the evolution of the disease. 9 Don’t forget to disinfect the probe between uses!

 

  • Treatment 1-8
    • Specific therapies are not currently available for treatment of Covid-19 infections, but studies are underway.
    • Supportive care includes IV fluids, 02 supplementation and nutrition, as needed. Plenty of emotional support for patients and their families will likely be needed during these times.
    • Antibiotics have been used in the majority of reported cases, either on admission or during hospitalization when superimposed bacterial pneumonia or sepsis could not be excluded.
      • Prescribe antibiotics against common community-acquired pneumonia (CAP) pathogens, including those associated with post-viral/influenza pneumonia such as Streptococcus pneumoniae (eg, ceftriaxone), and Staphylococcus aureus (eg, vancomycin or linezolid if MRSA is suspected) when concurrent CAP is suspected.
      • Prescribe antibiotics against common hospital-acquired pneumonia (HAP) (eg, vancomycin plus cefepime) when HAP is suspected.
    • Corticosteroids should be avoided because of the potential for prolonging viral replication, unless indicated for other reasons such as COPD exacerbation or septic shock. 1
    • Monitor for deterioration in clinical status even when your hospitalized patient has relatively minor symptoms. This is because progression to lower respiratory tract disease due to Covid-19 often develops during the 2nd week of illness (average 9 days).
    • ICU transfer may be necessary in up to 30% of hospitalized patients due to complications such as ARDS, secondary infections, and multi-organ failure.

 

Again, thank you for caring for the sick and be safe! Feel free to leave comments or questions.

 

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References

  1. CDC. Interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19). https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html
  2. Ruan Q, Yang K, Wang W, Jiang L, et al. Clinical predictors of mortality due to COVID-19 based on analysis of data of 150 patients with Wuhan, China. Intensive Care Med 2020. https://link.springer.com/article/10.1007/s00134-020-05991-x
  3. Holshue ML, BeBohlt C, Lindquist S, et al. First case of 2019 novel coronavirus in the United States. N Engl J Med 2020;382:929-36. https://www.nejm.org/doi/full/10.1056/NEJMoa2001191
  4. Huang C, Wang Y, Li Xingwang, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497-506. https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(20)30183-5.pdf
  5. Young BE, Ong SWX, Kalimuddin S, et al. Epideomiologic features and clinical course of patients infected with SARS-CoV-2 Singapore. JAMA, March 3, 2020. Doi.10.1001/jama.2020.3204 https://www.ncbi.nlm.nih.gov/pubmed/32125362
  6. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical chacteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020;395:507-13. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30211-7/fulltext
  7. Guan W, Ni Z, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl Med 2020, Feb 28, 2020. https://www.nejm.org/doi/full/10.1056/NEJMoa2002032
  8. Zhang J, Zhou L, Yang Y, et al. Therapeutic and triage strategies for 2019 novel coronavirus disease in fever clinics. Lancet 2020;8: e11-e12. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30071-0/fulltext 9.
  9. Peng QY, Wang XT, Zhang LN, et al. Findings of lung ultrasonography of novel corona virus pneumonia during the 2019-2020 epidemic. Intensive Care Med 2020. https://doi.org/10.1007/s00134-020-05996-
Key clinical pearls in the medical management of hospitalized patients with coronavirus (Covid-19) infection

What changes should I consider in my treatment of hospitalized patients with community-acquired pneumonia (CAP) in light of the 2019 guidelines of the American Thoracic society (ATS) and Infectious Diseases Society of America (IDSA)?

Compared to 2007,1 the 2019 ATS/IDSA guidelines2 propose changes in at least 4 major areas of CAP treatment in inpatients, with 2 “Do’s” and 2 “Dont’s”:

  • Do select empiric antibiotics based on severity of CAP and risk factors for methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (see related pearl on P4P)
  • Do routinely treat CAP patients who test positive for influenza with standard CAP antibiotics
  • Don’t routinely provide anaerobic coverage in aspiration pneumonia (limit it to empyema and lung abscess) (see related pearl on P4P)
  • Don’t routinely treat CAP with adjunctive corticosteroids in the absence of refractory shock

β-lactam plus macrolide is recommended for both non-severe and severe CAP.  β-lactam plus respiratory fluoroquinolone is an alternative regime in severe CAP, though not endorsed as strongly as β-lactam plus macrolide therapy (low quality of evidence).  Management per CAP severity summarized below:

  • Non-severe CAP
    • β-lactam (eg, ceftriaxone, cefotaxime, ampicillin-sulbactam and newly-added ceftaroline) plus macrolide (eg, azithromycin, clarithromycin) OR respiratory fluoroquinolone (eg, levofloxacin, moxifloxacin)
    • In patients at risk of MRSA or P. aeruginosa infection (eg, prior isolation of respective pathogens, hospitalization and parenteral antibiotics in the last 90 days or locally validated risk factors—HCAP has been retired), obtain cultures/PCR
    • Hold off on MRSA or P. aeruginosa coverage unless culture/PCR results return positive.
  • Severe CAP
    • β-lactam plus macrolide OR β-lactam plus respiratory fluoroquinolone (see above)
    • In patients at risk of MRSA or P. aeruginosa infection (see above), obtain cultures/PCR
    • Add MRSA coverage (eg, vancomycin or linezolid) and/or P. aeruginosa coverage (eg, cefepime, ceftazidime, piperacillin-tazobactam, meropenem, imipenem) if deemed at risk (see above) while waiting for culture/PCR results

Duration of antibiotics is for a minimum of 5 days for commonly-targeted pathogens and a minimum of 7 days for MRSA or P. aeruginosa infections, irrespective of severity or rapidity in achieving clinical stability.

For patients who test positive for influenza and have CAP, standard antibacterial regimen should be routinely added to antiinfluenza treatment.

For patients suspected of aspiration pneumonia, anaerobic coverage (eg, clindamycin, ampicillin-sulbactam, piperacillin-tazobactam) is NOT routinely recommended in the absence of lung abscess or empyema.

Corticosteroids are NOT routinely recommended for non-severe (high quality of evidence) or severe (moderate quality of evidence) CAP in the absence of refractory septic shock.

Related pearls on P4P:

2019 CAP guidelines on diagnostics:                                        https://pearls4peers.com/2020/02/14/what-changes-should-i-consider-in-my-diagnostic-approach-to-hospitalized-patients-with-community-acquired-pneumonia-cap-in-light-of-the-2019-guidelines-of-the-american-thoracic-society-ats-and-inf/ 

Anerobic coverage of aspiration pneumonia: https://pearls4peers.com/2019/07/31/should-i-routinely-select-antibiotics-with-activity-against-anaerobes-in-my-patients-with-presumed-aspiration-pneumonia/

References

  1. Mandell LA, Wunderink RG, Anzueto A. Infectious Disease Society of America/American Thoracic Society Consensus Guidelines on the Management guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44:S27-72. https://www.ncbi.nlm.nih.gov/pubmed/17278083
  2. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. Am J Respir Crit Care Med 2019;200:e45-e67. https://www.ncbi.nlm.nih.gov/pubmed/31573350

 

What changes should I consider in my treatment of hospitalized patients with community-acquired pneumonia (CAP) in light of the 2019 guidelines of the American Thoracic society (ATS) and Infectious Diseases Society of America (IDSA)?

Is neurotoxicity caused by cefepime common?

The incidence of cefepime-induced neurotoxicity (CIN) has varied from 1% to 15%.1 Potential clinical manifestations of CIN include delirium, impaired level of consciousness, disorientation/agitation, myoclonus, non-convulsive status epilepticus, seizures, and aphasia.1  Many of these signs and symptoms (eg, delirium) are common among hospitalized patients.

Although renal dysfunction and inadequately adjusted dosages are often cited as risk factors, one-half of patients develop suspected CIN despite apparently proper adjustment for renal function.In addition,  several case reports of CIN have involved patients with normal renal function. 2  A study of 1120 patients receiving cefepime found epileptiform discharges in 14 cases, most having normal renal function.3 Of interest, in the same study, the prevalence of epileptiform discharges was 6-fold higher than that of meropenem!

Proposed mechanisms for CIN include its avidity for central nervous system GABA-A receptors (higher than that of many beta-lactam antibiotics) combined with its high concentration in brain tissue.1 Renal impairment, decreased protein binding, and increased organic acid accumulation can increase transfer of cefepime across the blood brain barrier from an expected 10% to up to 45% of its serum concentration, further contributing to its neurotoxicity.4

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 References

 

  1. Appa AA, Jain R, Rakita RM, et al. Characterizing cefepime neurotoxicity: a systematic review. Open Forum Infectious Diseases 2017 Oct 10;4(4):ofx170. doi: 10.1093/ofid/ofx170. eCollection 2017 Fall. https://www.ncbi.nlm.nih.gov/pubmed/29071284
  2. Meillier A, Rahimian D. Cefepime-induced encephalopathy with normal renal function. Oxford Medical Case Reports, 2016;6, 118-120. https://academic.oup.com/omcr/article/2016/6/118/2362353
  3. Naeije G, Lorent S, Vincent JL, et al. Continuous epileptiform discharges in patients treated with cefpime or meropenem Arch Neurol 2011;68:1303-7. https://www.ncbi.nlm.nih.gov/pubmed/21987544
  4. Payne LE, Gaganon DJ, Riker RR, et al. Cefepime-induced neurotoxicity: a systematic review. Critical Care 017;21:276. https://www.ncbi.nlm.nih.gov/pubmed/29137682

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

Is neurotoxicity caused by cefepime common?

What is the clinical relevance of “SPICE” organisms?

“SPICE” often stands for the following bacterial species: Serratia spp, Providencia spp, indole-positive Proteae (e.g. Proteus spp. [not mirabilis], Morganella spp., Providencia spp.), Citrobacter spp., and Enterobacter spp.  Some have also included Pseudomonas spp (“P”).

These organisms (as well as Acinetobacter spp., at times “A” in SP”A”CE organisms) often have inducible chromosomal AmpC ß-lactamase genes that may be derepressed during therapy, conferring in vivo ß-lactam resistance despite apparent sensitivity in vitro (1,2). Because AmpC genes in clinical isolates are not routinely screened for in the laboratory, the following treatment approach to these organisms is often adopted (1).

Third generation cephalosporins (e.g. ceftriaxone and ceftazidime) are usually avoided irrespective of in vitro susceptibility. For less serious infections (e.g. urinary tract infections) or severe infections in carefully monitored clinically stable patients, piperacillin-tazobactam and cefepime in particular may be used due to their lower risk of induced resistance. For severe infections (e.g. pneumonia and bacteremia) in seriously ill patients, carbapenems (e.g. meropenem, imipenem-cilastatin) are often the drugs of choice. 

A small retrospective study of patients with infection due to SPICE organisms (about 50% with bacteremia) found cefepime to be as effective as meropenem, but cautioned its use when adequate source control has not been achieved (3). Fluroroquinolones and aminoglycosides may also be considered.

References

  1. MacDougall C. Beyond susceptible and resistant, part I: treatment of infections due to Gram-negative organisms with inducible ß-lactamases. J Pediatr Pharmacol Ther 2011;16:23-30. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3136230/
  2. Jacoby GA. AmpC ß-lactamases. Clin Microbiol Rev 2009;22:161-182. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2620637/
  3. Tamma PD, Girdwood SCT, Gopaul R, et al. The use of cefepime for treating AmpC ß-lactamase-producing Enterobacteriaceae. Clin Infect Dis 2013;57:781-8. https://academic.oup.com/cid/article/57/6/781/330020

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Contributed in part by Avi Geller, Medical Student, Harvard Medical School, Boston, MA

 

What is the clinical relevance of “SPICE” organisms?