Recent guidelines in antibiotics uses

Recent guidelines in antibiotics uses

1. RECENT GUIDELINES IN ANTIBIOTICS USES GUIDE- CANDIDATE- DR. A. THAKUR DR. ASHISH KUMAR BANDIL

2. INTRODUCTION First antibiotic, " the magic bullet " Penicillin is discovered in the year 1943, patients could be effective cured of many life-threatening infections.

3. SEVERE SEPSIS AND SEPTIC SHOCK Systemic inflammatory response syndrome (SIRS) Two or more of the following variables i . Fever > 38°C (100.4°F) or hypothermia < 36°C (96.8°F) ii. Tachypnea (>20 breaths/min) or PaCO2 < 32 mmHg iii. Tachycardia (heart rate >90 beats/min) iv. Leukocytosis or leucopenia : WBC > 12,000 cells/mm3, <4,000 cells/mm3 or > 10% immature band forms

4. SEVERE SEPSIS AND SEPTIC SHOCK IN ICU (CONT…) Sepsis : Systemic inflammatory response syndrome that occurs due to a “known or suspected” pathogen (bacteria, viruses, fungi or parasites) SEPSIS = INFECTION + SIRS

5. SEVERE SEPSIS AND SEPTIC SHOCK IN ICU (CONT…) Severe sepsis = Sepsis + Evidence of organ dysfunction or tissue hypoperfusion . Sepsis induced hypotension - sepsis with SBP <90 mm Hg or MAP <70 mm Hg or SBP decrease >40 mm Hg Septic shock - Sepsis induced hypotension that persists despite adequate fluid resuscitation, requiring vasopressors to maintain the blood pressure.

6. SOFA SCORE

7. SOFA SCORE (CONT…) Correlation of total score and hospital mortality- Serial SOFA scores were collected during the first 48 hours of admission.

8. CHOICE OF ANTIBIOTICS Depends on antibiotic susceptibility of the causative organism. There are some infections, which can be treated by one of several drugs. Use the most effective, least toxic and least expensive antibiotic for the precise duration of time needed to cure or prevent infection.

9. CHOICE OF ANTIBIOTICS(CONT…) Before antimicrobial prescribing consider the following : a. Which organism is likely to cause the disease? b. What is the clinical diagnosis and what other steps should be taken to reach diagnostic precision? c. Which antimicrobial agents are available and active against the presumed cause of the illness d. Check for factors, which will affect choice of drug and dose, e.g., renal function, interactions, allergy, pregnancy and lactation. e. Check that the appropriate dose is prescribed. f. What is the duration of treatment? g. Is treatment working?

10. EMPERIAL / PRESUMPTIVE THERAPY If the causative agent is not known and where delay in initiating therapy would be life threatening or risk serious morbidity, antimicrobial therapy based on a clinically defined infection is justified. According to WHO, presumptive treatment is a one-time treatment given for a presumed infection in a person, or group of people, at high risk of infection and the following points should be taken into consideration : a. Do not rush to treat. b. Antibiotics SHOULD be started only after sending appropriate cultures if facilities are available. c. Cover all possible microbial causes. d. Assess the factors affecting activity of antimicrobials such as renal excretion, interactions and allergy before prescribing antibiotics.

11. EMPERIAL / PRESUMPTIVE THERAPY(CONT…) e. Try to attain synergy f. Consider possible interaction with other drugs. g. Use less costly drugs where possible. h. Need for antimicrobial therapy should be reviewed on a daily basis. For most infections 5 – 7 days of antimicrobial therapy is sufficient. i . All IV antibiotics may only be given for 48 – 72 hours without review and consideration of oral alternatives . J. Once culture reports are available, the physician should step down to the narrowest spectrum, most efficacious and most cost effective option.

12. Treatment with antibiotic combinations In order to avoid antagonism between drugs and undesirable side effects of several antibiotics it is advisable to use a single drug where ever possible. There are situations however, when the use of antibiotic combination is desirable. The situations are: a. A temporary expedient during the investigation of an obscure illness. b. To prevent the development of bacterial resistance in long term therapy Example- treatment of tuberculosis. c. To achieve synergistic effect, e.g. in treating infective endocarditis. d. Mixed infection, when one drug is not effective against the pathogen. e. To permit a reduction of the dose of potentially toxic drug.

13. Reserve Antimicrobials These reserve antimicrobials will be made available following a recommendation from the Microbiology Department as per culture report or if included in an antimicrobial policy for a clinical specialty that has been agreed with antibiotic management team. eg - linezolid, vancomycin, colistin . The following criteria has been proposed to protect the Carbapenems and Linezolid from overuse – 1. Severe sepsis. 2. Clinical failure of other classes of antibiotics over 48 hours in terms of worsening inflammatory markers, un-resolving fever and new/worsening hemodynamic instability. 3. Underlying severe immuno-suppression – Neutropeniea , immuno-suppressive therapy, Diabetic Ketoacidosis (DKA) etc. 4. The organism is susceptible to only carbapenems / linezolid, as per culture report.

14. Reserve Antimicrobials(CONT…) The following criteria has been proposed for initiating Colistin – 1. Pan-resistant organism as per culture report with evidence of invasive disease – fever/ leucocytosis or culture from a sterile site. 2. Clinical failure of all other classes of antibiotics over 72 hours The following criteria has been proposed for initiating Rifampicin – 1. Empiric or proven TB as a part of ATT (4 drug regimen) Rifampicin should not be prescribed in our country for any treatment other than for Mycobacteria and for chemoprophylaxis of meningoccal meningitis in clinically indicated population. Rifampicin should not be prescribed alone as an anti-bacterial .

15. Reserve Antimicrobials(CONT…) The following criteria has been proposed for initiating Aminoglycoside s – I. The focus of infection is not lung or an anaerobic abscess. II. Only as a part of initial empiric regimen of a combination therapy – shall step down to single drug after culture report. III. Other safer drug options have been ruled out in a culture report.

16. Recommended measures to control spread of Multi-drug resistant organisms (MDRO) : i . Improved laboratory detection and reporting of MDRO ii. Enhanced infection surveillance and control in ICUs iii. Prevent spread by barrier precautions : Gowns and gloves iv. Hand Washing v. Restricted use of 3rd generation cephalosporins

17. Emergence of antimicrobial resistance in pathogens has become a matter of great public health concern. Antimicrobial resistance is well recognised as a global threat to human health. Infections caused by antimicrobial-resistant micro-organisms in hospitals are associated with increased morbidity, mortality and healthcare costs. Resistance has emerged due to- Irrational use of drugs Self-medication Misuse of drugs

18. HYPERSENSITIVITY Drug Allergy : One or more symptoms developed during or following drug administration including difficulty breathing, swelling, itching, rash, and anaphylaxis, swelling of the lips, loss of consciousness, seizures or congestion involving mucous membranes of eyes, nose and mouth. Drug Intolerance : One or more symptoms developed during or following drug administration including gastrointestinal symptoms e.g. nausea, vomiting, diarrhoea, abdominal pain and feeling faint.

19. Alert Antimicrobials To Prevent and Control the Emergence and Spread of Antimicrobial-Resistant Micro-organisms in Hospitals” one major strategic goal is to “define guidelines for use of key antibiotics” , (“Alert” antibiotics). 1. PIPERACILLIN - TAZOBACTAM Indication- Pneumonia or sepsis in neutropenic patients (+ Gentamicin) Septic shock Intra-abdominal infection- appendicitis, peritonitis. Moderate to severe skin and soft tissue infection.

20. Alert Antimicrobials(CONT…) 2. CARBEPENEMS only class of antimicrobials which remain effective against ESBL-producing isolates of E coli and Klebsiella species Imipenem is susceptible to degradation by the enzyme dehydropeptidase-1 (DHP-1) located in renal tubules and requires co administration with a DHP-1 inhibitor cilastatin . Meropenem and ertapenem are administered without a DHP-1 inhibitor Indication- Initial empiric treatment for severe, life-threatening infections (associated with multi-organ dysfunction, septic shock) caused by Gram-negative bacteria. Febrile neutropenia Ventilator associated / nosocomial pneumonia Pyelonephritis / complicated urinary tract infections Complicated intra-abdominal infections

21. Alert Antimicrobials(CONT…) 3. LINEZOLID Linezolid should only be prescribed after consulting an specialist or clinical microbiologist. Infections due to proven glycopeptide -insensitive Staphylococcus aureus or vancomycin -resistant enterococcus. To enable IV/oral switch from IV vancomycin (used for MRSA or MRSE) to oral linezolid (when patient’s discharge is possible and continuation treatment using combination rifampicin /trimethoprim is inappropriate. surgical site infections (e.g. large bowel surgery, vascular surgery, etc ). Poor IV access and a glycopeptide is indicated. Rare cases of hypersensitivity/allergy to the glycopeptides .

22. Alert Antimicrobials(CONT…) 4. VANCOMYCIN Indication- Serious (e.g. bacteraemia, osteomyelitis) coagulase negative staphylococcal and MRSA infections and penicillin resistant enterococcal infections Empiric therapy in febrile neutropenic patients not responding to first line therapy Continuous ambulatory peritoneal dialysis (CAPD) associated peritonitis Prosthetic valve endocarditis 5. TEICOPLANIN Teicoplanin is a suitable alternative to vancomycin for all indications for Vancomycin except meningitis: inability to tolerate vancomycin

23. Antimicrobial Guidelines For Various Infections

24. DIARRHEA Alteration in a normal bowel movement characterized by an increase in the water content, volume, or frequency of stools If diarrhoea present WITH vomiting, low grade fever with no mucus in stools think of viral infection . If diarrhoea present WITH vomiting, abdominal cramps, blood and mucus in stools WITH fever, think of bacterial infection . If diarrhoea present WITH blood and mucus in stool WITH no fever, think of amoebiasis . If profuse diarrhoea present (rice water stools) WITH vomiting, think of cholera . If diarrhoea present WITH excessive vomiting (especially if in more than one member of the household or group) think of food poisoning .

25. ENTERIC FEVER Confirmed case of enteric fever - patient with fever (38°C and above) that has lasted for at least three days, with a laboratory-confirmed positive culture (blood, bone marrow, bowel fluid) of S. typhi . Probable case of enteric fever- patient with fever (38°C and above) that has lasted for at least three days, with a positive serodiagnosis or antigen detection test but without S. typhi isolation.

26. A. GASTROINTESTINAL & INTRA-ABDOMINAL INFECTIONS

27. Continued…

28. Continued…

29. URINARY TRACT INFECTION Infections of the urinary tract caused by pathogens consistent with the clinical picture . E . coli is responsible for about 80-90% of UTI in the community. This is followed by Proteus sp., Klebsiella sp., Staphylococcus aureus , etc. In hospital acquired UTIs or in the presence of devices, Pseudomonas aeruginosa, Acinetobacter sp , Enterococci etc . Inpatients on long term catheters and antibiotic therapy, Candida sp is also implicated.

30. PERITONITIS SBP- Transudative ascitis with increased absolute PMN count ( i.e. , ≥250 cells/mm3 and without an evident intra-abdominal, surgically treatable source of infection.

31. ACUTE PANCREATITIS Routine use of prophylactic antibiotics in patients with severe AP is NOT recommended . The use of antibiotics in patients with sterile necrosis to prevent the development of infected necrosis is NOT recommended. Infected necrosis should be considered in patients with pancreatic or extrapancreatic necrosis who deteriorate or fail to improve after 7 – 10 days of hospitalization. In these patients, either ( i ) Initial CT-guided fine-needle aspiration (FNA) for Gram stain and culture to guide use of appropriate antibiotics or (ii) Empiric use of antibiotics after obtaining necessary cultures for infectious agents . In patients with infected necrosis, antibiotics known to penetrate pancreatic necrosis, such as carbapenems, quinolones, and metronidazole, may be useful in delaying or decreasing morbidity and mortality.

32. ACUTE PANCREATITIS(CONT…)

33. LIVER ABSCESS

34. FUNGAL INFECTIONS Routine antifungal prophylactic therapy in critically ill patients is NOT recommended. Fungal therapy is usually started based on positive cultures or systemic evidence of fungal infection. Treat according to identification and antifungal sensitivity of Candida isolate. Fluconazole IV/oral 800 mg OD first day (12mg/kg) and then 400 mg OD (6mg/kg from second day) if fluconazole naïve or sensitive Or 2nd line Liposomal Amphotericin B (for Candida krusei and C.glabrata as inherently resistant to Fluconazole); dose- IV 3mg/kg OD. or Caspofungin (It is inherently inactive against Zygomycetes , Cryptococcus, Fusarium and Trichosporon Spp ); dose: IV 70mg on Day 1 (loading), 50mg OD (<80kg) or 70mg OD (if >80kg) thereafter Moderate to severe hepatic dysfunction: reduce the subsequent daily dose to 35mg OD.

35. FEBRILE NEUTROPENIA CRITERIA Neutropenia-ANC<500/mm3 and expected to fall <500/mm3 in 48hrs Fever -single oral temperature of 38.3oC (101.0 F) on one occasion or 38C (100.40 F) on at least 2 occasions (1 hour apart) may not have usual signs of infection. Redness, tenderness and fever may be the only signs.

36. FEBRILE NEUTROPENIA(CONT…) Blood culture 2 sets Start IV Ceftazidime No need to add glycopeptide in the initial regimen (except in specific situations, given below Cefoperazone-Sulbactam / piperacillin-tazobactam ) OR Carbapenem ( meropenem / imipenem / doripenem ) No need to add glycopeptide in the initial regimen (except in specific situations, given below Haemodynamically Stable Haemodynamically Unstable

37. Reculture blood Add amikacin for 3 days Add colistin (instead of amikacin ) if indicated Inj Colistin (+/- Carbapenem ) + glycopeptide + Echinocandin /L- Ampho B Blood culture growing Gram negative bacilli with Patient afebrile – continue the empirical antibiotic till antibiotic sensitivity is available. Rationalise as per susceptibility profiles Reassess after 48 hours Blood culture negative Haemodynamically stable but still febrile Haemodynamically Unstable but still febrile

38. FEBRILE NEUTROPENIA(CONT…) When to add glycopeptides ? 1. Haemodynamic instability, or other evidence of severe sepsis, septic shock or pneumonia 2. Colonisation with MRSA or penicillin-resistant S. pneumonia 3. Suspicion of serious catheter-related infection e.g. chills or rigours with infusion through catheter and cellulitis around the catheter exit site 4. Skin or soft-tissue infection at any site 5. Positive blood culture for gram-positive bacteria, before final identification and susceptibility testing is available 6. Severe mucositis

39. FEBRILE NEUTROPENIA(CONT…) When to add empirical colistin in febrile neutropenic patients? 1. Haemodynamic instability. 2. Colonisation with carbapenem resistant gram-negative bacteria. 3. Previous infection with carbapenem resistant gram-negative bacteria. 4. GNB in blood, sensitivity pending, persistent fever with haemodynamic instability. Empirical Antifungal Therapy No response to broad spectrum antibiotics (3-5 days)-add L- Ampho B / echinocandin When a patient is located at a remote area and may not have access to emergency healthcare services

40. FEBRILE NEUTROPENIA(CONT…) Useful tips Febrile after 72 hrs -CT chest and consider empirical antifungal. If fever persists on empirical antibiotics, send two sets blood cultures/day for 2 days Unexplained persistent fever in otherwise stable patient doesn’t require change in empirical antibiotic regimen. Continue the regimen till ANC is >500 cells/mm3 If glycopeptide started as a part of empirical regimen, STOP after 48 hrs , if no evidence of Gram positive infection Antibiotic treatment should be given for at least seven days with an apparently effective antibiotic, with at least four days without fever.

41. Device Associated Infections Device associated infection (DAI)- An infection in a patient with a device ( e.g ., ventilator or central line) that was used within the 48-hour period before onset of infection. If the interval is longer than 48 hours, there must be compelling evidence that the infection was associated with device use. There is no minimum period of time that these devices must be in place for the infections to be considered device-associated. About 60-70% of nosocomial infections are associated with implanted medical devices (1). Biofilms act as a nidus for chronic infections which are recalcitrant to antimicrobial therapy. A thick biofilm is formed within 24 hours on the entire surface of these plastic devices even with a small initial number of bacteria spreading at a rate of up to 0.5 cm per hour.

42. Pathogen-specific antimicrobial therapy according to the pathogen isolated

43. Anti Microbial Resistance In this population of patients, 95% of cases of urinary tract infection are catheter related 87% of cases of bloodstream infection are associated with indwelling vascular catheters 86% of cases of pneumonia are due to mechanical ventilation

44. Central line associated blood stream infection (CLABSI) - Defined when a patient with a central line in place (or in the 48 hours after line removal) has a recognized pathogen cultured from one or more blood cultures that is not related to an infection at another site, or has at least one of the following signs or symptoms: fever >38°C, chills hypotension common skin contaminant is cultured from two or more blood cultures drawn on separate occasions, when signs, symptoms, and positive laboratory results are not related to an infection at another site.

45. Catheter related bloodstream infections (CRBSI) Positive semi quantitative (>15 colony-forming units [CFU]/catheter segment) or quantitative (>103 CFU/catheter segment) cultures whereby the same organism is isolated from the catheter segment and peripheral blood Simultaneous quantitative blood cultures with a ≥5:1 ratio CVC versus peripheral. Differential period of CVC culture versus peripheral blood culture positivity where CVC culture flags positive before peripheral blood culture by >2 hours.

46. Treatment of CRBSI Removal of the indwelling device or catheter Salvage of the device Antimicrobial chemotherapy- After appropriate cultures of blood and catheter samples are done, empirical i /v antimicrobial therapy started. Vancomycin is usually recommended as the empirical antimicrobial therapy in areas with an increased incidence of methicillin-resistant staphylococci. Linezolid is not recommended as empirical therapy. Daptomycin acts as an alternative for institutions where MRSA isolates have vancomycin minimum inhibitory concentration (MIC) values of >2 μg / mL. In the absence of MRSA , penicillinase -resistant penicillins , such as nafcillin or oxacillin , or a first generation cephalosporin like cefazolin should be used.

47. VAP In the intensive care unit (ICU), affecting 8 to 20% of ICU patients and up to 27% of mechanically ventilated patients. Common pathogens include Pseudomonas species and other highly resistant Gram-negative bacilli, the Enterobacteriaceae , staphylococci, streptococci, and Haemophilus species. Quantitative cultures of bronchoalveolar lavage (BAL) seem to be fairly equivalent in diagnosing VAP, while blood cultures are relatively insensitive.

48. Prevalent antimicrobial resistance status According to the International Nosocomial Infection Control Consortium (INICC)- 87.5% of all Staphylococcus aureus HCAIs were caused by methicillin-resistant strains, 71.4% of Enterobacteriaceae were resistant to ceftriaxone and 26.1% to piperacillin – tazobactam ; 28.6% of the Pseudomonas aeruginosa strains were resistant to ciprofloxacin, 64.9% to ceftazidime and 42.0% to imipenem .

49. ICMR surveillance for resistant pathogen-

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