Module 7 antimicrobials v2
- 1. HEALTH programme EMERGENCIES SARI CRITICAL CARE TRAINING ANTIMICROBIAL THERAPY AND ITS MODIFICATION AFTER DIAGNOSTIC TEST INTERPRETATION 20 January 2020
- 2. HEALTH programme EMERGENCIES Learning objectives At the end of this lecture, you will be able to: • Prescribe empiric antimicrobial therapy to patients with SARI and suspected severe pneumonia/sepsis: COVID-2019 • Describe antiviral therapy for patients with 2019-nCoV infections. • Describe antiviral therapy for influenza, if also circulating • Understand how to interpret diagnostic test results and modify management. |
- 3. HEALTH programme EMERGENCIES Prescribing antimicrobial therapy for patients with SARI (1/3); severe illness • Give appropriate, empiric broad-spectrum antimicrobials as soon as possible of recognition of patient with SARI and sepsis/severe pneumonia (in the emergency area when possible). • Preferably after the clinical specimen collection (upper and/or lower respiratory samples and blood cultures). • Each hour delay in administration of effective antimicrobial therapy in septic shock is associated with increased mortality.
- 4. HEALTH programme EMERGENCIES Prescribing antimicrobial therapy for patients with SARI (2/3): severe illness ● Empiric therapy may include one or more effective drugs to treat all likely pathogens: – i.e. antibiotics for suspected bacterial pathogens, antiviral for suspected viral pathogen (if effective antiviral is known), antifungal for suspected fungal pathogen, etc.). ● For patients with septic shock, can consider combination therapy: – i.e. using two antibiotics of different antimicrobial classes aimed at most likely bacterial pathogen.
- 5. HEALTH programme EMERGENCIES Antivirals for 2019-nCoV • There are no known effective antivirals for coronavirus infections. • Various candidates with potential anti-SARS-CoV-2 activity are being evaluated for clinical trial protocols. • Use of unregistered or unproven therapeutics for COVID-2019 should be done under strict monitoring and ethical approval.
- 6. HEALTH programme EMERGENCIES Priority agents and ongoing clinical trials • Priority agents for clinical trials: – Remdisivir: broad spectrum antiviral (in vitro and in vivo data, clinical safety in EVD) – Lopinovir/ritonavir: could be quickly repurposed • China: – Ritonavir/Lopinavir vs placebo: finished enrollment – Remdisivir vs placebo: mild and severe patients, enrolling • USA: – Remdisivir vs placebo-hospitalized patients: just started enrollment https://www.who.int/blueprint/priority-diseases/key-action/novel-coronavirus/en/
- 7. HEALTH programme EMERGENCIES Other therapeutics in earlier development • Need more development/early phase: – Monoclonal or polyclonal antibodies. – Plasma (hyperimmune globulin) • Not prioritized: – Ribavirin due to toxicity and potential harm in SARS 2003 – Chloroquine (lack of data) List to be updated as regularly as evidence becomes available
- 8. HEALTH programme EMERGENCIES Can be used at national level: select sponsor
- 9. HEALTH programme EMERGENCIES Prescribing antivirals for patients with influenza virus infection ● For patient with or at risk of severe seasonal influenza A or B viruses or those with zoonotic influenza A virus infection: – Give antiviral (NAI, oseltamivir) as soon as possible. • earlier treatment has greater clinical benefit than later treatment or no treatment. – Can give at any stage of active disease when ongoing viral replication is anticipated or proven. – Influenza viral replication can be prolonged in the lower respiratory tract in critically ill patients.
- 10. HEALTH programme EMERGENCIES Prescribing oseltamivir (1/2) • WHO recommends for patient with severe or at risk for severe, seasonal influenza virus infection and zoonotic influenza virus infection. • Oral capsule or suspension, that can be given via nasogastric or orogastric tube in ventilated patients. • Dose is 75 mg twice daily for 5 days in adults Give as soon as possible to patient with suspected or confirmed influenza virus infection of all ages.
- 11. HEALTH programme EMERGENCIES Prescribing oseltamivir (children) (2/2) • Dose in children up to 40 kg is 3 mg/kg twice daily for 5 days • Dose in children over 40 kg is adult dose (75 mg twice daily for 5 days) • Available as oral suspension (6 or 12 mg/mL) and tablets (30 mg, 45 mg, 75 mg)
- 12. HEALTH programme EMERGENCIES| Interpretation of test results • Detection of virus depends on multiple factors: – time of sample collection from illness onset – source of specimen (upper vs lower) – type of virus – diagnostic testing assay – storage and transportation conditions – host factors. • Thus, there can be false negative results. If you have a high clinical and epidemiologic suspicion of influenza, DO NOT stop treatment and IPC measures for influenza virus following a negative result. Repeat testing, sampling lower tract preferably.
- 13. HEALTH programme EMERGENCIES When to give antibiotics?
- 14. HEALTH programme EMERGENCIES Prescribing antibiotics therapy for patients with SARI: severe and critical illness ● Dose antimicrobials optimally based on pharmacokinetic principles: – i.e. take into account renal or hepatic function – i.e. take into account volume of distribution. ● Ensure drug adequately penetrates into tissue presumed to be source of infection (i.e. lungs): – e.g. gentamycin and daptomycin are not reliable CAP treatments in adults.
- 15. HEALTH programme EMERGENCIES Choose the correct antibiotics (1/2) • Patient’s factors: • at risk for resistant pathogens (i.e. recent IV antibiotics) • at risk for opportunistic infections (i.e. immunosuppression, co-morbidities or presence of invasive devices). • Epidemiologic factors: • Community acquired, hospital acquired, etc. • Pathogen factors: • prevalent pathogens in community, hospital, etc. • susceptibility and resistance patterns of prevalent pathogens.
- 16. HEALTH programme EMERGENCIES Choose the correct antibiotic (2/2) • Refer to local guidance for treatment recommendations: – based on local antibiograms. • If none available, adapt international guidance: – Infectious Disease Society of America (IDSA): • CAP in adults published in 2007, revision pending • CAP in child older than 3 months of age, published 2011. – British Thoracic Society (BTS): • CAP in adults, published 2014. – NICE guidelines: • CAP in adults, published in 2015.
- 18. HEALTH programme EMERGENCIES Examples of antibiotic regimens for severe CAP: IDSA and BTS guidelines Combination therapy: •B-lactam e.g. ampicillin-sulbactam, cefuroxime, cefotaxime or ceftriaxone •and antibiotic against atypical pneumonia (e.g. macrolide or doxycycline) or respiratory flouroquinolone (e.g. levofloxacin). If community-acquired methicillin-resistant S. aureus (CA-MRSA) suspected: •add vancomycin or linezolid. If immunosuppressed (i.e. PL-HIV): • consider anti-pneumocystis treatment (e.g. sulfamethoxazole/trimethoprim). In pregnant women the use of macrolides, cephalosporins and penicillins are safe. Do not use flouroquinolones or doxycyline.
- 19. HEALTH programme EMERGENCIES Paediatric recommendation from IDSA Combination therapy: •ampicillin or penicillin G for fully immunized child if local epidemiology documents lack of substantial high-level penicillin-resistance for invasive S. pneumoniae. •Or third generation cephalosporin (e.g. cefotaxime or ceftriaxone) for non-fully immunized child, known high-level, penicillin-resistance for invasive S. pneumoniae or life-threatening infection. And antibiotic against atypical pneumonia (i.e. macrolide). If community-acquired S. aureus suspected: •add vancomycin or clindamycin based on local susceptibility data. Flouroquinolones and doxycyline are not used to treat CAP in children.
- 20. HEALTH programme EMERGENCIES Paediatric recommendation from WHO Child Handbook Severe pneumonia: •ampicillin or penicillin G + gentamicin. If no signs of improvement within 48 hours: • switch to third generation cephalosporin (e.g. cefotaxime or ceftriaxone). If no improvement in 48 hours and suspect community-acquired S. aureus: •switch to cloxacillin and gentamicin. If HIV infection or exposure to HIV, suspect PjP pneumonia: •child < 12 months, give high dose co-trimoxazole and sulfamethoxazole •child 1–5 years, give PjP treatment only if clinical signs of PjP. Flouroquinolones and doxycyline are not used to treat CAP in children.
- 21. HEALTH programme EMERGENCIES Examples of antibiotic regimens for HAP from IDSA/ATS guidelines: 2016 Risk factors for MDR pathogen*: •Prior intravenous antibiotic use within 90 days •Admission from nursing home Anti-pseudomonal coverage: •cephalopsorin with antipseudomonal activity(e.g. ceftazidine, cefepime) or •carbapenem (e.g. meropenem or imipenem not ertapenem) or •B-lactam/B-lactamase inhibitor (e.g. piperacillin/tazobactam) or •aztreonam (if penicillin allergic) plus (double coverage can be considered if > 10% isolates are MDR) •flouroquinolone (e.g. levofloxacin (high dose) or ciprofloxacin) or •aminoglycoside (e.g. tobramycin, amikacin, gentamicin). AND anti-methicillin-resistant S. aureus antibiotic if patient is at high risk of mortality (need for ventilator support due to pneumonia and sepsis) or > 20% isolates are MRSA: •vancomycin or linezolid. ** Aliberti S et al. Clinical Infect Dose. 2012;54(4):470-478
- 22. HEALTH programme EMERGENCIES Antimicrobial de-escalation (1/3) • Re-assess the antimicrobial regimen daily for potential de- escalation. • Narrow once causative agent is identified, sensitivities established: – continue most appropriate antimicrobial that targets the pathogen. • In the absence of clinical or microbiological indication of bacterial infection consider discontinuation of antibiotics.
- 23. HEALTH programme EMERGENCIES Antimicrobial de-escalation (2/3) • If no causative agent, de-escalation should still occur, but strict criteria for de-escalation are not available. • Considerations include: – signs of clinical improvement (i.e. once shock resolved) – signs of infection resolution (i.e. procalcitonin). • 5–10 days of duration of treatment is adequate for most serious infections associated with sepsis. • Longer treatment courses may be appropriate in patients with slow clinical response, undrainable foci and certain infections (i.e. S. aureus bacteremia).
- 24. HEALTH programme EMERGENCIES Antimicrobial de-escalation (3/3) Appropriate antibiotic use minimizes the risk of superinfection, drug resistance, adverse effects and costs. Infectious disease consultation may be advisable if drug-resistant pathogens suspected or detected.
- 25. HEALTH programme EMERGENCIES Reasons for clinical deterioration
- 27. HEALTH programme EMERGENCIES Corticosteroids and viral pneumonia • Corticosteroid use is associated with various negative clinical outcomes, such as: - prolonged viral replication, avascular necrosis, promotion of immunosuppression leading to bacterial or fungal super-infection, psychosis, hyperglycaemia, and increased mortality. • Consider its use only for specific indications such as exacerbation of asthma/COPD or suspected adrenal insufficiency or refractory shock or co-infection with PjP. If used, use only low dose. There is NO proven role for corticosteroids in acute influenza pneumonia or SARS/MERS infection.
- 28. HEALTH programme EMERGENCIES Summary • At this stage, there are no known antiviral therapies for 2019-nCoV infection. All therapeutics should be given, under strict monitoring and ethical approval, preferably randomized controlled trial. • If influenza virus infection is suspected (i.e. seasonal influenza A or B viruses are known or suspected to be circulating among persons in the community or the patient is at risk for avian influenza A virus infection), then treat SARI patient empirically with oseltamivir,. • SARI patients with sepsis or severe pneumonia, should also be treated with appropriate antibiotics as soon as possible with a clear de-escalation plan.
- 29. HEALTH programme EMERGENCIES Contributors Dr Cheryl Cohen, National Institute for Communicable Diseases (NICD), Johannesburg, South Africa Dr Shabir Madhi, University of the Witwatersrand, Johannesburg, South Africa Dr Niranjan Bhat, Johns Hopkins University, Baltimore, USA Dr Michael Ison, Northwestern University, Chicago, USA Dr Tim Uyeki, Centers for Disease Control and Prevention, Atlanta, USA Dr Janet Diaz, WHO Consultant, San Francisco CA, USA Dr Fred Hayden, University of Virginia, USA Dr Owen Tsang, Hospital Authority, Princess Margaret Hospital, Hong Kong, SAR, China Dr Leo Yee Sin, Tan Tock Seng Hospital, Communicable Disease Centre, Singapore Dr Vu Quoc Dat, Hanoi Medical University and National Hospital of Tropical Disease, Hanoi Viet Nam Dr Natalia Pshenichnaya, Rostov State Medical University, Russian Federation Acknowledgements