use of antimicrobials in neonatal practice
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The document discusses three case scenarios involving newborn infants admitted to the NICU with prematurity, low birth weight, respiratory distress, and sepsis. For the first case, the recommended choice of antibiotic is ampicillin and gentamicin. For the second case where the baby develops lethargy, the next choice of antibiotic discussed is vancomycin plus an aminoglycoside. The third case involves a baby with late onset sepsis who is treated with multiple courses of antibiotics and develops recurrent infections. Empiric antibiotic therapy for newborns and the bacterial etiology of neonatal sepsis is also summarized.
use of antimicrobials in neonatal practice
- 1. DR AFROZA ISLAM SHUMA DR YASHU SAH Resident ,year -3 Neonatology BSMMU.
- 2. Case Scenario-1 • D/O Luna, inborn, was admitted to NICU, BSMMU at 1 hour of age with the complaints of Prematurity(34wks) LBW(1700gm). Mother had history of PROM for 2 days before delivery. On examination baby was pink in room air, with good reflex & activity, SPO2 -95%, normothermic, euglycemic & well perfused, vitals-stable, systemic examination revealed normal findings. • What is the choice of antibiotic for this patient?
- 3. Case Scenario-2 S/O Rima, inborn, was admitted to NICU of BSMMU at 30min of age with the complaints of prematurity (33wks), VLBW(1300gm) and respiratory distress soon after birth. Baby was managed with IV fluid, inj ampicillin and gentamycin and CPAP care. At 82hrs of PNA baby developed lethargy . On examination baby was pink in room air, with poor reflex & activity, SPO2-95%, normothermic, euglycemic & well perfused, other vitals-normal and systemic examination- normal findings. Sepsis screen was positive and blood C/S- showed no growth of organism. • Now what is the next choice of antibiotic for this patient?
- 4. Case Scenario-3 • S/O Sumaiya, outborn, admitted into NICU on 21 days of age with diagnosis of preterm(30wk) , VLBW(1230g), RDS (resolved) with LONS. On admission baby was Pink with 2l/min O2, with good reflex & activity, vitals were stable, SPO2-95% with 2l /min O2, euglycemic & well perfused. Baby was managed with IV fluid along with OG feeding, inj cefepime and colistin. In previous hospital baby was treated with inj ceftazidime and amikacin (day 1-5) and inj meropenem and vancomycin (day 6-16).
- 5. • Then during hospital course in BSMMU baby developed culture positive LONS 3 times on PNA Day-24 Acinetobacter +ve (sensitive to netilmycin and colistin), on D-28 Klebsiella +ve (sensitive to colistin) & D-31, Klebsiella +ve (sensitive to colistin and chloramphenicol).He was treated with Piperacillin and Tazobactum + Linezolid - D26 – D29 = 3 days ,Colistin + Netilmicin - D30- D37 = 7 days Colistin + Ciprofloxacin- D38= 10days.
- 6. Multiple culture positive organism Antibiotic resistance ANTIBIOTICS !!!!! Our challenges
- 7. Use of Antimicrobials in Neonatal Practice
- 8. Contents • Factor predisposing to the development of neonatal infection • Why antimicrobials are required? • Factors to be considered before prescribing antimicrobials • Common antimicrobials used in Neonatal Practice • Current scenario- Prevalence of organism ,Spectrum of antibiotic coverage and sensitivity pattern • Common newborn infections • Measures to be taken-Rational use of antimicrobials • guideline of antimicrobials • Take home messages
- 9. Introduction • Prevalence of infection in newborn is high than any other period of life due to- - Physiological & immune system immaturity - Survival of preterm babies has been increased • Antimicrobials use in the NICU is 10 times more frequent than in the rest of the hospital beds. • Virtually all extremely low birth weight infants receive antimicrobials and for all other birth weight groups admitted to the NICU the vast majority are treated with antimicrobials.
- 10. Factor predisposing to the development neonatal infection • Newborn are less capable of responding to infection due to immunologic deficiencies. • Infectious agents can be transmitted from mothers to fetus or newborn by diverse modes. • Infections are often undiagnosed because mother was either asymptomatic or had non-specific sign symptom. • Clinical manifestation are nonspecific including subclinical infection.
- 11. • Coexisting condition complicate the diagnosis and management. • A wide variety of etiological agent e.g bacteria, virus, fungi, protozoa etc. • Premature , VLBW babies need prolong NICU stay which increase risk for acquired infection.
- 12. Why antimicrobials are required ? • Suppressed immune system of neonates leads to higher incidence of infection • Invasive procedure • Surgical procedure • Use of parenteral fluid • Use of catheters (UAC, UVC, ETT) Reference: Meyer E et al. Intensive Care Med.2006; 30:1089-96
- 13. Antibiotic Prescription is Common in NICU • Antibiotics are greatly over prescribed in the NICU. • In a point prevalence study of 29 NICUs, 47% of 827 infants were receiving at least one antibiotic on the day of the survey. Reference: Grohskopf L et al.Pediatr Infect Dis J. 2005;24:766-773
- 14. Effect of antibiotics on the neonate • Newborn: sterile gut. • Normal flora: early days of life. • Antibiotics : delay in microflora colonisation with most anaerobes, importantly Bifidobacterium and Lactobacillus. • Antibiotics also limit the number of bacterial species in the normal flora. • An inverse dose- response between the duration of antibiotics and the number of species in the flora. • Bacterial overgrowth of other species • A major role in restricting the diversity and the volume of the normal flora thus reducing protection from invading pathogens
- 15. Factors to be considered before prescribing antimicrobials • Dose and frequency : as per body weight ,gestation and post natal age. • Route :oral and IM unreliable, so I/V is considered. • Coverage of both Gram positive and negative- choose based on local bacterial C/S. • Combination of drugs should use for synergistic effect.
- 16. • Adjust dose and frequency -if hepatic and renal impairment. • Co-morbidities e.g.- congenital anomalies, AKI . • Choice of empirical antibiotics- dependent on: Protocols, local previous C/S. • Avoid reserve drugs like Vancomycin, ciprofloxacin, Teicoplanin etc • The duration of therapy is dependent upon culture results and clinical course. • Downgrade antibiotics as per C/S report
- 17. ● Drugs- Interaction- ceftriaxone is not recommended for use with hyper-bilirubinemia and hyper-albuminemia as it displace bilirubin from albumin binding site, PHB like enzyme inducer. Storage- temp, duration. Administration- proper precaution e.g.- amphotrericin B, vancomycin. Drugs manufacturing, e.g- expired date.
- 18. Precautions to be taken Aminoglycosides: • Nephrotoxic- 8- 26% developed mild reversible renal impairment if use > 7-10 days • Increased toxicity if used with other nephrotoxic drugs e.g.- frusemide, vancomycin. Monitor renal function and trough level. • Ototoxic – gentamycin causes vestibular and amikacin causes auditory damage • Never be placed with same infusion fluid if used with penicillin – because on prolonged contact, positively charged aminoglycosides form an inactive complex with negatively charged penicillin.
- 19. Precautions to be taken • Vancomycin : • Nephrotoxic & ototoxic- use with caution. • Rapid infusion- rash and hypotension ( Red man syndrome), so infuse slowly over 1 hr. • Phlebitis - extremely irritant to the tissues. Should decrease rate and dilute appropriately. • Linezolid : • expensive drug, should reserve. used in MRSA, VRE. • Monitor BP when co administer with dopamin, dobutamine
- 20. Avoid redundant coverage Category of use Examples Double anaerobic coverage Meropenem and metronidazole Double gram positive coverage Ampicillin and vancomycin
- 21. Oral Antibiotics in the Management of Serious Neonatal Bacterial Infections in Developing Country Communities They reviewed the evidence for treatment of neonatal infections in developing countries with oral antibiotics. • this strategy has resulted in substantial reductions in neonatal mortality . • Parenteral therapy should be used for treatment of serious neonatal infections whenever possible. In settings in which this is not possible, oral antibiotic therapy is superior to no antibiotic therapy. (Pediatr Infect Dis J 2009;28: S31–S36)
- 22. Simplified Antibiotic Treatment (SAT) • Safety and Efficacy of Simplified Antibiotic Regimens for Outpatient Treatment (SAT) of Suspected Severe Infections in Neonates and Young Infants (Bangladesh) • The Simplified Antibiotic Treatment (a randomized controlled) Trial in Bangladesh provided evidence that simpler antibiotic regimens involving 2 days of injection followed by oral antibiotics for treatment of clinically severe infection in young infants are as efficacious as the standard regimen involving 7 days of injectable antibiotics, thus expanding treatment options for many more infants who live in resource poor settings where hospital care is not accessible. The treatment failure rates (9.8%, 8.3%, and 8.1%), death any time before day 15 follow-up (1.5% to 1.8%), and relapse rates (<2%) similar among all three treatment arms.
- 23. The Lancet Global Health , vol-3, p 279-87, May 2015
- 24. The Lancet Global Health , vol-3, p 279-87, May 2015, The Pediatric Infectious Disease Journal Vol 32,Num 9,Supplement,Sep 2013
- 25. Common antimicrobials used in Neonatal Practice
- 27. Classification and Sites Of Antibiotics Action
- 28. Choices of Antibiotic Beta β-lactum antibiotics Penicillin Natural (Benzylepenicillin, Phenoxymethylpenicillin) Methicillin/Flucloxacillin The Aminopenicillins Carboxypenicillin (Ticarcillin) and Ureidopenicillins (piperacillin) Cephalosporins Monobactum Carbapenems
- 29. The Aminopenicillin (Ampicillin) Same spectrum of activity as the natural penicillins with additional Gram negative cover against Enterobacteriaceae. Ureidopenicillin (Piperacillin) These are particularly active against Gram negative organisms, especially Pseudomonus , used with tazobactam( b- lactamase inhibitor)
- 30. Use of Piperacillin-Tazobactum in NICU: Evidences • Piperacillin-tazobactam (PIP/TAZO) has been extensively used in adults with nosocomial infections. • PIP/TAZO may safely be used in neonate as an empiric treatment for serious infections in hospital environments where resistance to common first-line antimicrobials has emerged. • The change from ceftazidime to piperacillin/tazobactam is associated with a decrease in the incidence of Klebsiella sepsis. References: Wolf MF, Simon A. Expert Opin Drug Metab Toxicol. 2009 Jan;5(1):57-69. Fidel-Rimon O, Friedman S, Gradstein S. Acta Paediatr 2003 Oct;92(10):1205-7.
- 31. 4th generation Cephalosporin: Cefepime Evidences of use in NICU • Excellent broad spectrum activity. Have little anti- anaerobic activity and none against Enterococcus spp. • Useful in critical pneumonia, soft and bone tissue infection, UTI. • It eradicates organisms which have shown resistance to other β-lactum antibiotics. • Monotherapy gives both the good clinical response and an excellent microbiological clearance. Ref: Sukhbir Kaur Shahid. Clinical Medicine Review in Therapeutic.2010; 2: 1-10
- 32. Carbapenem (Meropenem,Imipenem) Broadest antibiotic activity of β-lactum antibiotics and include activity against anaerobes. Glycopeptides Vancomycin Effective against MRSA and resistant enterococci. Only enters CSF in the presence of inflammation.
- 33. Oxazolidinones: Linezolid • Only oxazolidinone currently available for clinical use. • Activity against Gram positive organisms such as MRSA, Vancomycin resistant Enterococci (VRE),penicillin resistant Strepto pneumoniae(PRSP).
- 34. Use of Linezolid in NICU: Evidences • Linezolid is promising agent for the treatment of mainly resistant Gram positive infection after treatment failure. • Effective for the treatment of pneumonia, skin and soft tissue infection, CNS infection and osteoarticular infection. • Linezolid is effective, well tolerated in neonatal age group. • Safe and effective alternative to vancomycin in preterm infants. Ref: John Dotis et al. International Journal of Infectious Disease 14(2010)e638-e648. G. Giannouli et al. Linezolid treatment of nosocomial resistant gram positive bacteria in neonates. Kocher S. Int J Antimicrob Agent. 2010 Aug;36(2):106-10.
- 35. Aminoglycosides Gentamicin Very effective in Gram negative sepsis and body fluid infection, exerting synergism with β- lactum antibiotics. Fluroquinolones Ciprofloxacin • Greater activity against Gram negative organisms. • Can be used against respiratory pathogens in an empirical manner.
- 36. Colistin • Colistimethate intravenous administration appears to be safe and efficacious for multidrug-resistant Gram- negative infections in neonates, including preterm and extremely low birth weight neonates. • Aerosolized colistin was tolerable and safe, and it may be an adjunctive treatment option for MDR gram-negative bacterial VAP in neonates. References: Celik IH, Oguz SS, Demirel G.Eur J Pediatr.2012 Feb;171(2):311-6. Jajoo M, Kumar V, Jain M.Pediatr Infect dis J. 2011 Mar;30(3):218-21.
- 37. Common infections of newborn and antimicrobials
- 38. Sepsis
- 39. Bacterial Etiology of Neonatal Sepsis In developed country • Early Onset Sepsis – GBS and E coli – Recently decrease in Gram positive organisms (GBS) and increase in Gram negative organisms • Late Onset Sepsis – Coagulase Negative Staph (CONS) – GBS – Staph Aureus In developing country • Gram negative organisms – Klebsiella, Escherichia coli, – Pseudomonas, – Acinetobacer, Enterobacter, Citrobacter. • Gram positive less common – Staphylococcus Aureus – Coagulase negative staphylococci (CONS) – Streptococcus pneumoniae, – Streptococcus pyogenes
- 40. Empiric Antibiotic Therapy • Treatment is most often begun before a definite causative agent is identified. Cover both gram (+)ve and (-)ve organism. • For EONS - Ampicillin and gentamicin. • For suspected LONS - Ampicillin and gentamicin, cefotaxime can be added only when there is a concern for meningitis. • In nosocomial sepsis, flora of the NICU must be considered. • For staphylococcal coverage - vancomycin plus an aminoglycoside such as gentamicin or amikacin .
- 41. • About 70% of these isolates may not be covered by the empiric regimen of ampicillin and gentamicin. (Zaidi et al, international journal of pediatrics, 2011) • Third-generation cephalosporins should be avoided. • In the developed countries- CoNS is the predominant nosocomial pathogen. They use vancomycin as empirical therapy. • The Cochrane review : study by Miall-Allen et al Timentin (ticarcillin and clavulanic acid) monotherapy with a combination of flucloxacillin and gentamicin in 28 neonates with suspected LOS. No difference in outcome (mortality/treatment failure) between the two groups.
- 42. Empiric Antibiotic Therapy • Therapy should be unit specific • Determined by the prevalent spectrum of etiological agents and their antibiotic sensitivity pattern • Should be modified according to sensitivity reports • Choice is dependent upon the probable source of infection
- 43. Duration of therapy • Mainly based on culture and sensitivity results, clinical course, Serial lab investigation. • Chowdhary et al. compared the effectiveness of 7- day versus 14-day antibiotic therapy in 69 infants with blood culture-proven bacterial sepsis. • More treatment failures in 7-day group. • Treatment failures occurred in subjects with S.aureus infection receiving 7-day course. Journal of Tropical Pediatrics Vol. 52, No. 6, 2014
- 44. Antibiotic use protocol NICU, BSMMU Antibiotics 1st line Ampicillin+ Gentamicin 2nd line Ceftazidime + Amikacin 3rd line (reserve) Meropenem, Ciprofloxacin, Vancomycin, Cefepime, Clarithromycin, Netilmicin, Imipenem, Piperacillin-Tazobactam, Colistin In case of suspected meningitis Cefotaxim + Amikacin or Meropenem + Amikacin
- 45. Management protocol of newborn, doctors handbook, BSMMU
- 46. Suggested Antibiotic Regimens Organism Antibiotic Bacteremia Meningitis GBS Ampicillin 10 d 14-21 d E. coli Cefotaxim or ampicillin and gentamicin 10-14 d 21 d CONS Vancomycin 7 d 14 d Klebsiella, Serratia Cefotaxime or meropnem and gentamicin 10-14 d 21 d Enterobacter, Citrobacter Cefepime or meropenem and gentamicin 10-14 d 21 d Enterococcus Ampicillin or vancomycin and gentamicin 10 d 21 d Listeria Ampicillin and gentamicin 10-14 d 14-21 d Pseudomonus Ceftazidime or piperacillin/tazobactum and gentamicin 14 d 21 d MRSA Vancomycin 10-14 d 21 d Manual of Neonata Care by John P. Cloherty
- 47. Fungal Infections • The overall incidence of fungal septicemia on neonatal units is increasing because of both increased survival of VLBW neonates and use of broad spectrum antibiotics. • Transmission may be vertical ( from maternal to vaginal infection/colonisation) or horizontal. • 3rd most common cause of late-onset sepsis in NICU (high risk)
- 49. Risk factor for fungal infection
- 50. Classification and Sites Of Antibiotics Action
- 51. Common Fungal Infection Oral candidiasis: common in breast fed infant with ductal candidiasis with mothers breast. • nystatin oral suspension-1ml every 6 hrly for 10-14 days or fluconazole Candidal diaper dermatitis: 2% nystatin or 2% mionazole ointment or 1% clotrimazol cream Systemic candidiasis: • Amphotericin B 0.5 -1mg/kg/day for 7-14 days after negative blood c/s or 3 wks if end organ affected. But causes phlebitis, hypokalemia, hypomagnesemia, hyperglycemia, nephrotoxicity. so given slowly over 2hrs. • Or Fluconazole 6mg/kg/day or flurocytosine
- 52. Selective fluconazole prophylaxis in high‐risk babies to reduce invasive fungal infection Brian A McCrossan, Elaine McHenry, Fiona O'Neill, GraceOng, and David G Arch Dis Child Fetal Neonatal Ed, v.92(6); Nov 2007 • Fluconazole 6 mg/kg for 3 weeks. Dose interval every 72 h during the first 2 weeks of life. Thereafter, dose interval reduced to every 48 h until 3 weeks old when daily fluconazole is given. • 6/33 babies eligible for prophylaxis developed culture proven Candida sepsis before compared with no (0/31) babies after the guideline was implemented (p=0.03). • Selective antifungal prophylaxis has reduced invasive fungal sepsis.
- 53. Viral infection • Most of this infection are acquired by vertical transmission, but some are the result of cross infection postnatally. • Indication of antiviral therapy: • HIV infection and AIDS • Herpes viruses • Varicella – zoster infection • Enteroviruses • Neonatal hepatitis e.g.- hepatitis B • TORCH infection- congenital rubella, CMV, toxoplasmosis
- 55. Anti –viral Drugs Anti herpes virus agents- used in- HSV-1,HSV-2, VZV, shingles • acyclovir/ valacyclovir • Famciclovir / Penciclovir • Ganciclovir/ cidofovir Anti cytomegalovirus Agents - CMV • Gancyclovir/ Valgancyclovir
- 56. Antiretroviral Agents • 1.Nucleoside Reverse Transcriptase inhibitors (NRTIs)- Zidovudine, lamivudine, stavudine • 2. Nonnucleoside Reverse Transcriptase inhibitors ( NNRTIs)-Nevirapine, Delavirdine, Efavirenz • 3. Protease inhibitors-Indinavir, Ritonavir, Saquinavir • Anti-Hepatitis Agents • hepatitis B : Lamivudine, Adefovir and tenovir • hepatitis C : interferon alpha and Ribavirin
- 57. Burden and Impact of Infection • Globally, serious neonatal infections cause an estimated 36% of neonatal deaths . • In settings with very high mortality, neonatal infections are estimated to cause 40% to 50% of all neonatal deaths. • Five to 30% of all neonatal infections are nosocomial infection. • Overall, 30% neonates clinically suspected to have late onset sepsis have positive blood culture. • Antibiotics in NICUs consume 30% of the budget in tertiary care hospital. Singh et al.2000; 117:1496-99 Gerbending G. Clin Updates in Infect Dis.2000;5:1-4 Singh S A et al.J Trop Pediatr. 2003; 49:235-9
- 58. Bangladesh Scenario • In a rural setting sepsis constituted 12% of direct causes of neonatal deaths • A study in Dhaka slums showed sepsis as a direct cause of neonatal deaths in 20% cases Ref:Chowdhury HR, Thompson S, Ali M, Alam N et al. J Health Popul Nutr.2010; 28(4):375-382, Khatun F, Rasheed S, Moran AC et al. BMC Public Health 2012, 12:84, Liu L, Johnson HL, Cousens S et al. Lancet 2012;379:2151-6, CHERG/WHO/UNICEF for distribution of causes of neonatal and under-five deaths (published in Liu et al, Lancet 2014)
- 59. BSMMU SCENARIO
- 60. • Results: Organisms were isolated in 124/ 559 (22.2%) of the collected blood samples. LONS 113/124 (91.1%), remaining were early onset sepsis (EOS). • Acinetobacter (46%) was found to be the most common organism in LONS followed by Klebsiella (37.9%) and E.Coli (6.4%). • Most of the organisms were resistant to 1st and 2nd line antibiotics. Colistin exhibits the highest sensitivity (93.5%) followed by Tazobactum- piperacillin (54.8%), and then Ciprofloxacin (44.3%), Netilmicin (43.5%) and Imipenem (41.9%). Bacteriological profiles and antibiotic susceptibility pattern in NICU (Oct 2014 - Dec 2017)
- 61. Changing pattern of antibiotic sensitivity of organism for most commonly sensitive 5 antibiotics
- 62. Sepsis in BSMMU NICU 44% 36.80% 33.50% 31.4% 32% 20.40% 20.70% 23% 22.04% 18.50% 0% 5% 10% 15% 20% 25% 30% 35% 40% 45% 50% 2015 2016 2017 2018 2019 (upto May) Sepsis Culture+ve
- 63. Bacterial Etiology of Neonatal Sepsis Acinetobacter 51% Klebsiella 32% Pseudomonas 11% E.coli 2% Staphylococcus 3% Others 1%
- 64. Antibiotic sensitivity pattern of 2019 0% 20% 40% 60% 80% 100% 120%
- 66. Irrational use of antimicrobials • Lack of skills and knowledge • Inappropriate unethical promotion of medicines by pharmaceutical companies & Profits from selling medicines • Unrestricted availability of medicines • Unaffordable medicines • Lack of coordinated national or institutional pharmaceutical policy
- 67. Consequences of irrational use of antimicrobials • Emergence of antimicrobial resistance. • Increase infection related mortality and morbidity. • Increase rate of nosocomial and overall infection. • Adverse drug reactions and medication errors. • Economic burden. • Eroded patient confidence.
- 68. Measures to be taken • Rational use of antimicrobials: • Rational use of medicines refers to the correct, proper and appropriate use of medicines. Rational use requires that patients receive the appropriate medicine, in the proper dose, for an adequate period of time, and at the lowest cost to them and their community. (WHO)
- 69. Antibiotic Policy • Components of rational use of antibiotic. • Problems with selecting appropriate antibiotic use.
- 70. Components of Rational Use of Antibiotic 1. Timely antibiotic management 2. Appropriate selection 3. Appropriate administration and de-escalation 4. Consultation with infectious disease specialist 5. Local data and evidences
- 71. 1. Timely antibiotic management • Accurately identify patients who needs antibiotic therapy • Obtain culture prior therapy • Administer antibiotic without delay • Specify the duration of therapy
- 72. 2. Appropriate selection • Make empiric choice based on local epidemiology. • Do not give therapy with overlapping activity
- 73. 3. Appropriate administration and de-escalation • Give the right dose and interval • Monitor for toxicity and adjust accordingly e.g- aminoglycosides need renal dose adjustment • Review culture results and adjust accordingly • Stop therapy promptly if culture reports no growth.
- 74. 4. Availability of expertise • Infectious disease specialist • Implementation of antimicrobial stewardship
- 75. 5. Local Data and Evidences • Assigned person to monitor antibiotic utilization, adverse events related to antibiotic use, bacterial etiology and their culture and sensitivity pattern. • Set antibiotic policy according to changing pattern of culture and sensitivity report • Create local evidence • Review the policy
- 77. Guidelines of antimicrobial therapy • Exclude contaminant positive blood culture. • Give antibiotic with a narrower spectrum or lower cost. • If possible, a single sensitive antibiotic must be used, the exception being Pseudomonus. • If baby worsened with sensitive antibiotic, select an alternative. • If the empirical antibiotics are resistant but the neonate has improved clinically. Careful assessment must be made.
- 78. Guidelines of antimicrobial therapy • One must not continue with antibiotics with in vitro resistance in case of Pseudomonus, Klebsiella and MRSA; and in cases of CNS infection and deep seated infection. • If no antibiotic has been reported sensitive, therapy must be changed to ‘moderately sensitive’ antibiotics at higher permissible dose. Use a combination in such cases.
- 79. Take Home Message !! • Suspected sepsis- send sepsis screen and blood culture; start 1st line I/V antibiotics without delay. • Downgrade or upgrade antibiotics as per C/S report • If no response within 48–72 hours of starting treatment, repeat blood C/S and change antibiotic therapy with appropriate choice and duration. • Use antimicrobials judiciously. • Monitoring for toxicity and adjust therapy e.g.- monitor renal function. • Review antibiotic policy every 6 month.
Editor's Notes
- #64: It is important to know the causative organism to implement effective therapy.