Handbook of. Antimicrobial Use at JIPMER. Edited by. Dr Subhash C.Parija Dr Sujatha Sistla Dr Jharna Mandal

Handbook of Antimicrobial Use at JIPMER Edited by Dr Subhash C.Parija Dr Sujatha Sistla Dr Jharna Mandal Department of Microbiology JIPMER - Pondicherry 2013

Contents Page GI and intra Abdominal Infections...5-7 CVS Infections... 8 Skin and soft tissue Infections...9 Bone and joint Infections...10 Respiratory Infections...11-12 Genitourinary Infections...13 CNS Infections...14 Ocular Infections...15 Dental Infections...16 Empiric antibiotic therapy for ICU...17-21 Treatment of Patients with Fever and Neutropenia...22-24 Changes made in the handbook- an entire section which deals with empiric antibiotic therapy in febrile neutropenia and one section dedicated to empiric therapy in the ICU. Certain new class of antibiotics have been included so that the pressure on certain groups of antibiotics are minimized like the carbapenems.

OBJECTIVES OF THE HANDBOOK The appropriate use of antimicrobials is an essential part of patient safety and deserves careful oversight and guidance. Antimicrobial resistance is an evolutionary phenomenon and the selection of resistant pathogens is significantly associated with antimicrobial use. Antimicrobial resistance results in increased morbidity, mortality, and costs of health care. Prevention of the emergence of resistance and the dissemination of resistant microorganisms will reduce these adverse effects and their attendant costs. We therefore urge everyone to restrict our use of antimicrobial agents. In this revised edition, we have added a few sections on the empiric treatment of febrile neutropenia and in the intensive care units. We hope that this second edition of the Handbook of Antimicrobial Use at JIPMER would address some of the pending issues of the last edition. We are very grateful to all our colleagues who gave their valuable suggestions in making of this edition of the handbook. There are bound to be errors and we would welcome all feedback so that future editions can be corrected. We hope that this handbook would act as a basic reference to the clinicians in prescribing antibiotics and help streamline the management of common infections encountered in the hospital.

GI and Intra Abdominal Infections Condition Etiology (likely Antibiotics Alternative/ pathogens) Comments Acute Viral nil If diarrhea persists gastroenteritis Enterotoxigenic and beyond 2 days or in pathogenic E.coli,non immunosuppressed typhoidal salmonella patients- Ciprofloxacin 500mg bd X 5 days Cholera V. cholerae Cap Doxycycline 300 Prompt rehydration mg, single dose (6mg/ essential kg, maximum 300 mg Tab Ciprofloxacin 1gm single dose (30mg/ kg, maximum 1 gm) Bacillary Shigella dysentery Tab Cefixime 400mg od In children, continue X 5 days(8mg/kg/day) feeding and add zinc Tab Ciprofloxacin 500 mg supplementation bd X 5 days Amoebic Entamaoeba Metronidazole 400mg dysentery histolytica tds for 10 days Giardiasis Giardia lamblia Tinidazole 2gm 1 dose Typhoid fever S. Typhi or Paratyphi A Outpatients- Inj Ceftriaxone 2gm Tab Ciprofloxacin 750 mg I.V. od for 14 days bd for 14 days Inj Chloramphenicol 500mg qid for 14 days Amoxycillin oral/im/iv (1gm-2gm) qid for14 days Cholangitis Enterobacteriacae Cefoperazone-sulbactum Piperacillin 2gm IV BD -Tazobactam 4.5 gm i.v. tds 7-10 days Anaerobes Metronidazole 500 mg I.V. tds 5

GI and Intra Abdominal Infections Condition Etiology (likely Antibiotics Alternative/ pathogens) Comments Acute Community-acquired Often an cholecystitis acute cholecystitis Cefuroxime 1.5 gm tds inflammatory but of mild-to-moderate or Ceftriaxone 1-2 gm non-infectious severity every 12-24 hours disease: If infection suspected, antibiotics to cover Enterobacteriacae Community-acquired acute cholecystitis of severe physiologic disturbance, advanced age, or immunocompromised state Acute cholangitis following bilio-enteric anastamosis of any severity Health careassociated biliary infection of any severity Cefoperazone-sulbactum or Piperacillin-Tazobactam 3.375 gm 8 th hourly, Ciprofloxacin 400 mg 12 th hourly, Levofloxacin 750 mg OD, or Cefepime 2 gm every 8-12 hours, each in combination with Metronidazole 500mg 8th - 12th hourly Cefoperazone-sulbactum or Piperacillin-Tazobactam, Ciprofloxacin, Levofloxacin, or Cefepime, each in combination with Metronidazole Cefoperazone-sulbactum or Piperacillin-Tazobactam, Ciprofloxacin, Levofloxacin, or Cefepime, each in combination with Metronidazole, Vancomycin added to each regimen 6

GI and Intra Abdominal Infections Condition Etiology (likely Antibiotics Alternative/ pathogens) Comments Spontaneous Enterobacteriacae Cefoperazone-sulbactum or If S.pneumoniae bacterial (most often E.coli) Piperacillin-Tazobactam suspected peritonitis Crystalline Penicillin or I.V. Ceftriaxone Secondary Enterobacteriacae Cefoperazone-sulbactum or Drainage of abscess peritonitis B. fragilis Piperacillin Tazobactam (bowel Enterococcus sp. with Metronidazole perforation), and Ampicillin for Intra Enterococcus abdominal abscess H. pylori Omeprazole, 20mg bd 14 days associated + Clarithromycin 500mg disease, p. o bd +Amoxicillin 1gm gastric MALT1 bd p.o lymphomas Amoebic liver Entamoeba histolytica Metronidazole Ultrasound guided abscess I.V.500mg tid / 800mg drainage in case of p.o tid for 10 days large abscesses, followed by Diloxanide imminent rupture furoate 500 mg p.o. for or no response to 10 days medical treatment Please send appropriate sample for culture and sensitivity and de-escalate wherever possible as per the sensitivity. 7

CVS Condition Etiology (likely Antibiotics Comments pathogens) Infective Penicillin Inj CP 120-180 lakh 2 week regimen only endocarditis (native susceptible units I.V.Q 4-6 hours or for uncomplicated valve) Streptococcus Inj Ceftriaxone 2gm I.V cases of native viridians viridans od for 4 weeks Alternate valve I.E due to CP + Gentamicin 1mg/ highly Penicillin kg I.V. Q 8 th hourly -susceptible Patients allergic to S. viridians viridans Penicillin should receive Vancomycin Enterococcus sp. S. S. viridians viridans resistant to penicillin CP 240 lakh units Culture negative Ampicillin 2 gm I.V. Q 4 hr + Gentamicin 1mg/kg I.V. Q 8 hr Infective MSSA Inj. Cloxacillin 2gm IV. endocarditis Q 4h + (prosthetic valve) Rifampicin 600mg P.O.BD+ Gentamicin 1mg/kg I.V. Q 8h for 6weeks MRSA Inj. Vancomycin 15mg/ kg I.V. Q 12h + Rifampicin 300mg P.O. Q 8h Gentamicin 1mg/kg I.V. Q 8h for 6 weeks Please send appropriate sample for culture and sensitivity and de-escalate wherever possible as per the sensitivity. 8

Skin and Soft Tissue Condition Etiology (likely Antibiotics Comments pathogens) Cellulitis Streptococcus Cloxacillin 500- pyogenes 1000mg P.O. 6 th Staphylococcus hourly for 7-10 days aureus OR Cephalexin 500mg P.O Q 6 h for 7-10 days Furunculosis S. aureus Topical Mupirocin, Cloxacillin Fusidic acid or 500mg P.O Q 6 Framycetin H for 7-10 days Diabetic foot - mild S. aureus Cloxacillin 500mg P.O (localized cellulitis, no Q 6 h for 7-10 days systemic symptoms) OR Cephalexin 500mg P.O Q 6 h for 7-10 days Diabetic foot- moderate to Polymicrobial - Inj Cefazolin 1gm in suspected severe (limb threatening - S. aureus, I.V. Q 8h renal severe cellulitis/gangrene/ S. pyogenes, + Gentamicin 5mg/ involvement SIRS) Gram negative kg I.V. Q 24h + substitute bacilli, anaerobes Metronidazole 500mgIV Gentamicin Q8H with Ciprofloxacin Clindamycin plus 400 mg i.v.q12h metronidazole Necrotizing fasciitis S. pyogenes CP 20lakh units I.V. Q4h + Clindamycin 600mg I.V. Q6h Please send appropriate sample for culture and sensitivity and de-escalate wherever possible as per the sensitivity. 9

Bone and Joint Infections Condition Etiology Antibiotics Comments Acute S.aureus Cloxacillin 1gm I.V For optimal treatment osteomyelitis Q4h OR microoraginisms should be (non-diabetic) Cefazolin 1gm Q8h identified by blood culture or aspiration or bone biopsy Duration - 6 weeks. Can switch to oral therapy once clinical improvement occurs Acute Polymicrobial Surgical debridement will osteomyelitis in enhance cure rate diabetics Definitive treatment guided by bone biopsy/ deep curettings (NOT superficial swabs) culture and susceptibility studies Duration of therapy -minimum 6 weeks after surgical debridement Chronic No empiric therapy Definitive therapy guided osteomyelitis by bone biopsy culture and susceptibility results Septic arthritis S. aureus Cloxacillin 1gm I.V. Q4h OR Cefazolin 1gm I.V Q8h Duration - 2-4 weeks Prosthetic joint No empric therapy Obtain culture of peri infections unless acutely ill prosthetic tissue/ synovial In severely ill patients, fluid. Vancomycin 15mg/kg Avoid culturing superficial I.V Q12h + Gentamicin wound/ sinus tracts 1mg/kg I.V. Q8h + Rifampicin 300mg P.O. Q8h Please send appropriate sample for culture and sensitivity and de-escalate wherever possible as per the sensitivity. 10

Respiratory Infections Condition Etiology Antibiotics Comments Acute pharyngitis Viral Benzathine Penicillin Most adults with Group A beta 12 L units I.M. 1 dose symptoms of acute hemolytic OR pharyngitis have a self streptococci(gabhs) Penicillin VK 500 mg limited illness for which P.O. Q8h for 10 days symptomatic therapy Amoxicillin 500mg with saline gargles and P.O. Q8h for 10 days analgesics will suffice In Penicillin Limit antibiotic usage allergic patients, only for patients Erythromycin 500 mg likely to have GABHS P.O.Q6h for 10 days infection (fever, tonsillar exudates, no cough, tender cervical lymph nodes) Throat swab cultures NOT recommended for routine evaluation of pharyngitis Acute epiglottitis H.influenzae Ceftriaxone 1gm I.V. Airway management OD for 7-10 days Ludwig s angina, Polymicrobial (oral Clindamycin 600mg Vincent s angina anaerobes) I.V. Q8h Airway management Alternative Surgical drainage Amoxicillin- Clavulanate 1000mg P.O bd Acute bronchitis Viral Not required Acute bacterial S. pneumoniae Amoxicillin 500mg Antibiotics to be given if rhinosinusitis H.influenzae P.O tds for 10-14 patient is symptomatic M. catarrhalis days (facial pain, purulent nasal discharge) for 7-10 days Acute bacterial S. pneumoniae Doxycycline 100mg Azithromycin 500mg exacerbation H.influenzae P.O. bd for 1 day P.O. od for 5 days or of COPD M. catarrhalis followed by 100mg od Co-amoxyclav 625mg (outpatients) for 5-7 days or bd for 5 days Cotrimoxazole DS bd for 5-7 days 11

Respiratory Infections Acute bacterial S. pneumoniae Azithromycin 500mg Inj Co- Amoxyclav 1.2 exacerbation H.influenzae P.O. od for 5-7 gm Q8h for 5-7 days of COPD M. catarrhalis, days or Switch to oral when (inpatients) aerobic GNBs Co-amoxyclav 625 clinically appropriate mg bd for 5-7days Community S. pneumoniae Azithromycin 500mg Tab Co-Amoxyclav acquired H.influenzae P.O. od for 5 days or 1gm bd +Azithromycin pneumonia Atypical pathogens Doxycycline 100mg 500mg od for 7 days P.O. bd for 7 days Community S. pneumoniae Inj Co- Amoxyclav Inj Cefotaxime 1gm acquired H.influenzae 1.2 gm Q8h for 5-7 Q8h or pneumonia Atypical pathogens days + Inj Ceftriaxone 2gm (hospitalized but Inj Azithromycin 500 od + inj Azithromycin not in ICU, NOT mg od for 5-7 days 500mg od for 5-7 days CRITICALLY Switch to oral when ILL) clinically appropriate Lung abscess Anaerobes Inj Ceftriaxone Inj Ceftriaxone 2gm od or aspiration S.pneumoniae 2gm od plus inj PLUS inj Metronidazole pneumonia H.influenzae Clindamycin 600mg 500mg Q8h or Q8h Inj Crystalline Penicillin switch to oral when 2 million units Q4h clinically stable treat for 4-6 weeks Please send appropriate sample for culture and sensitivity and de-escalate wherever possible as per the sensitivity. 12

Genitourinary Infections Condition Etiology Antibiotic Comments Acute Escherichia coli Ciprofloxacin 500mg BD, Alternateuncomplicated P.O for 5 days Nitrofurantoin 100mg cystitis in Nnon P.O. BD for 7 days pregnant women Acute Escherichia coli Amikacin 15mg/kg I.V Ertapenem 1gm I.V pyelonephritis Q24H for 7 days (mild Q24H (no underlying illness) or 14 days( GU disease) severe illness) Complicated UTI E.coli, Cefoperazone-sulbactum Catheter-sulbactum cefoperazone-sulbactam (underlying GU Proteus disease) Pseudomonas Piperacillin-tazobactam Piperacillin-tazobactum Acinetobacter Foley Catheter catherter Gram negative Treat only when patient Urine sample for associated UTI bacilli has systemic symptoms culture to be obtained through catheter port and NOT from urine bag Note: Asymptomatic bacteruria to be treated only in pregnancy, childhood or in patients with urinary tract abnormalities or obstruction Please send appropriate sample for culture and sensitivity and de-escalate wherever possible as per the sensitivity. 13

CNS Infections Condition Aetiology Antibiotics Comments Acute bacterial S.pneumoniae (CP Inj Ceftriaxone 2gm Dexamethazone 10m meningitis sensitive) Q12h I.V. for 10-14 g I.V Q6h for 4 days H.influenzae days First dose 15 minutes before the first dose of antibiotic S.pneumoniae (CP Inj Ceftriaxone 2gm resistant) Q12h I.V. for 10-14 days + Inj Vancomycin 500mg I.V Q6h for 10-14 days Gram negative organisms (other than Pseudomonas) Pseudomonas Listeria Inj Ceftriaxone 2gm Q12h I.V. for 21 days Inj Ceftazidime 2gm I.V Q8h for 21 days Inj Ampicillin 2gm I.V Q4h for 10 days+inj Gentamicin 7.5mg/ kg I.V Q8h for 21 days Brain abscess Mixture of aerobes Inj Ceftriaxone Treat until resolution and anaerobes 2gm I.V. Q12h +Inj Amikacin 500mg IV Q8h + inj Metronidazole I.V500mg I.V Q8h Ventriculitis Pseudomonas, Inj Imipenem-Cilastatin Acinetobacter, MRSA 750mg IV Q12h+ Inj Vancomycin 1gm IV Q12h Please send appropriate sample for culture and sensitivity and de-escalate wherever possible as per the sensitivity. 14

Ocular Infections Condition Etiology (likely Antibiotics Comments pathogens) Acute Streptococcus al antibiotics - Cloxacillin dacrocystitis pneumoniae 250-500mg po qid Staphylococcus Topical antibiotics aureus - Tobramycin 0.3% Ophthalmic solution 1 drop qid (or) Ciprofloxacin 0.3% 1 drop bd iv Ciprofloxacin 200mg bd in paediatric cases bital cellulitis Streptococcus Inj. Ceftriaxone 1-2g iv species q12hrly + Inj. Vancomycin S. aureus 1g iv q12hrly; to add Haemophilus metronidazole 15mg/kg influenzae type b iv loading then 7.5mg/kg Polymicrobial iv 6hrly for chronic orbital infections with cellulitis when anaerobic involvement of infection suspected. anaerobes more common in patients aged 16 and above Conjunctivitis Neonates Simple bacterial For prophylaxis Chlamydia conjunctivitis: against trachomatis 0.3% Ciprofloxacin eye secondary S. aureus drops 8-10 times a day bacterial H.influenzae 0.3% ciprofloxacin eye infections in S. pneumoniae ointment at night case of viral Children Adult chlamydial conjunctivitis H. influenzae conjunctivitis: - 0.3% S. pneumoniae Azithromycin 1g single dose ciprofloxacin eye S. aureus daily drops 5 times Adults a day S.aureus 0.3% Coagulase-negative ciprofloxacin eye Staphylococcus ointment at night organisms H. influenzae S. pneumoniae Please send appropriate sample for culture and sensitivity and de-escalate wherever possible as per the sensitivity. 15

Dental Infections Condition Etiology (likely Antibiotics Comments pathogens) Odontogenic Anaerobic For simple infections: infections streptococci Penicillin 500mg qid for 5-7 days Eubacterium plus Bacteroides Metronidazole 500mg tid/qid for melaninogenicus 5-7 days Fusobacterium For complex infections: Amoxicillin 500mg tid for 5-7 days Augmentin 500mg tid for 5-7 days Antibiotic regimen prior to dental treatment to prevent infective endocarditis Amoxicillin 2g 1h before procedure Cefazolin 1g iv 1h before procedure Please send appropriate sample for culture and sensitivity and de-escalate wherever possible as per the sensitivity. 16

Empiric antibiotic therapy for ICU Patient risk stratification Patient type I Community acquired infection (CAI) Patient coming to the ICU with CAI No contact with healthcare system No prior antibiotic treatment No procedures done Patient young (<65 years) with no or few co-morbid conditions Patient type II Healthcare associated infection/nosocomial infection Contact with health care system (e.g. Recent hospital admission, nursing home, dialysis without invasive procedure within last 90 days) Recent antibiotic therapy-with within last in last 90 90 days days Minimum procedures done Patient old (>65 years) with few co-morbidities Patient type III Healthcare associated infection/nosocomial infection Long hospitalization and/ or invasive procedures within last 90 days Recent & multiple antibiotic therapies- with in last 90 days Patient old (>65 years) within multiple co-morbidities Major invasive procedures done Structural lung disease, AIDS, Neutropenia other severe immunodeficiency Please send appropriate sample for culture and sensitivity and de-escalate wherever possible as per the sensitivity. 17

Blood Stream Infections Before Culture s are available After culture s are available Escalation De-escalation Patient type I Patient type II Patient type III Inj. Amoxycillinclavulanate plus Inj. Amikacin Ceftriaxone plus Inj. Amikacin If non-esbl/mssa then treat as per the susceptibility If ESBL positive or MRSA positive then treat as type II If non-esbl/ MSSA then treat per the susceptibility ESBL positive: Continue the same as above MRSA: Vancomycin (Linezolid only when vancomycin is contraindicated) Isolation of Candida: Fluconazole If patient does not respond then treat as in type III If non-esbl/ MSSA then treat as type I or treat per the susceptibility Inj. Amoxycillinclavulanate plus Inj. Amikacin Cefoperazonesulbactam Cefoperazonesulbactam Piperacillintazobactam ESBL positive: Continue the same as above MRSA: Vancomycin (Linezolid only when vancomycin is contraindicated) Isolation of Candida: Fluconazole Only when all others are found resistant- Cefepimetazobactam Carbapenem (Imipenemcilastatin,Meropenem) If a carbapenemase producer : Colistin Antifungal- (Voriconazole/ Amphotericin B) If non-esbl/ MSSA /noncarbapenemase producer then treat as type I or treat as per the susceptibility 18

Pneumonia Patient Type I Patient type II Patient type III Before culture s are available Inj Amoxycillinclavulanate plus inj Azithromycin Inj ceftriaxone plus Inj Azithromycin Cefoperazonesulbactam (add Inj.metronidazole if aspiration suspected) Cefoperazonesulbactam Piperacillin tazobactam (add Inj.metronidazole if aspiration suspected) Consider adding vancomycin only if strong clinical indication of MRSA After culture s available If non-esbl/mssa then treat per the susceptibility ESBL positive: Continue the same as above MRSA: Vancomycin (Linezolid only when vancomycin is contraindicated) Isolation of Candida: Fluconazole ESBL positive: Continue the same as above MRSA: Vancomycin (Linezolid only when vancomycin is contraindicated) Isolation of Candida: Fluconazole Escalation De-escalation If ESBL positive or MRSA positive then treat as type II If non-esbl/ MSSA then treat per the susceptibility 19 If patient does not respond then treat as in type III If non-esbl/ MSSA then treat as type I or treat per the susceptibility Only when all others are found resistant: Cefepime-tazobactam Carbapenem (Imipenem-cilastatin,Meropenem) If a carbapenemase producer : Colistin Antifungal- (Voriconazole/ Amphotericin B) If non-esbl/mssa/ non-carbapenemase producer then treat as type I or treat as per the susceptibility

UTI Patient type I Patient type II Patient type III Before culture s available After culture s available Escalate De-escalate Amikacin Ceftriaxone Non-ESBL / MSSA: continue the same as above If ESBL positive or MRSA positive then treat as type II If non-esbl/mssa then treat per the susceptibility Amikacin Cefoperazonesulbactam ESBL positive: Continue the same as above MRSA: Vancomycin (Linezolid only when vancomycin is contraindicated) Isolation of Candida: Fluconazole If patient does not respond then treat as in type III If non-esbl/ MSSA then treat as type I or treat per the susceptibility Amikacin Cefoperazonesulbactam ESBL positive: Continue the same as above MRSA: Vancomycin (Linezolid only when vancomycin is contraindicated) Isolation of Candida: Fluconazole Only when all others are found resistant- Cefepimetazobactam Carbapenem (Imipenem-cilastatin,Meropenem) If a carbapenemase producer : Colistin Antifungal- (Voriconazole/ Amphotericin B) If non-esbl / MSSA / noncarbapenemase producer then treat as type I or treat as per the susceptibility Please send appropriate sample for culture and sensitivity and de-escalate wherever possible as per the sensitivity. 20

Complicated Intra-abdominal infections Before Culture s available After culture s are available Escalation De-escalation Patient type I Patient type II Patient type III Inj. Amoxycillinclavulanate plus Inj. Amikacin plus metronidazole Ceftriaxone plus Inj. Amikacin plus metronidazole If non-esbl/ MSSA then treat per the susceptibility If ESBL positive or MRSA positive then treat as type II If non-esbl/ MSSA then treat per the susceptibility Inj. Amoxycillinclavulanate plus Inj. Amikacin plus metronidazole Cefoperazonesulbactam plus metronidazole/ ESBL positive: Continue the same as above MRSA: Vancomycin (Linezolid only when vancomycin is contraindicated) Isolation of Candida: Fluconazole If patient does not respond then treat as in type III If non-esbl/ MSSA then treat as type I or treat per the susceptibility Cefoperazonesulbactam plus metronidazole Piperacillin- tazobactam plus metronidazole ESBL positive: Continue the same as above MRSA: Vancomycin (Linezolid only when vancomycin is contraindicated) Isolation of Candida: Fluconazole Only when all others are found resistant- Cefepime-tazobactam Carbapenem (Imipenem-cilastatin,Meropenem): If a carbapenemase producer : Colistin Antifungal- (Voriconazole/ Amphotericin B) If non-esbl/mssa/ non-carbapenemase producer then treat as type I or treat as per the susceptibility NOTE: It may be noted that the following antibiotics can be prescribed only by the HOD or Professor or Additional professor: Cefepime Piperacillin-tazobactam Cefepime-tazobactam Meropenem Vancomycin Linezolid 21 22

Treatment of Patients with Fever And Neutropenia Principles Empirical antibiotic therapy should be administered promptly to all neutropenic patients at the onset of fever or any other new signs and symptoms of infection Antibiotics chosen should: Provide adequate coverage of Pseudomonas aeruginosa Be based on local antimicrobial susceptibility patterns of frequently identified bacterial Pathogens Low risk Solid organ malignancy with no organ dysfunction Age<60 years No comorbid illness High risk All haematological malignancies, solid organ malignancies with organ dysfunction Age>60 years Presence of comorbid illness Initial empirical antibiotic therapy : Low-risk patients should receive initial oral antibiotics: Levofloxacin plus amoxicillin-clavulanate in combination is recommended. High-risk patients require hospitalization for IV empirical antibiotic therapy; monotherapy with an antipseudomonal β-lactam agent, such as cefepime, a carbapenem (meropenem or imipenem-cilastatin), or piperacillin-tazobactam, is recommended. Other antimicrobials (aminoglycosides, fluoroquinolones, and/or vancomycin) may be added to the initial regimen for management of complications (eg, hypotension and pneumonia) or if antimicrobial resistance is suspected or proven. First line: Ceftazidime +amikacin cefepime+ amikacin Second line : Piperacillin-Tazobactum tazobactam + amikacin Cefepime-tazobactum tazobactam + amikacin Meropenem. Vancomycin (or other agents active against aerobic grampositive cocci) is not recommended as a standard part of the initial antibiotic regimen for fever and neutropenia. These agents should be considered for specific clinical indications, including suspected catheter-related infection, skin or soft-tissue infection, pneumonia, or hemodynamic instability. Vancomycin plus 1 or 2 antibiotics, if criteria for use of Vancomycin is met: As above + Vancomycin. 22

Modifications of initial antibiotic therapy: Modifications to initial empirical therapy may be considered for patients at risk for infection with the following antibiotic-resistant organisms, particularly - if the patient s condition is unstable or if the patient has positive blood culture [methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococcus (VRE), extended-spectrum b-lactamase (ESBL) producing gram-negative bacteria, and carbapenemase-producing organisms, including Klebsiella pneumoniae carbapenemase (KPC)]. Modifications to the initial antibiotic regimen should be guided by clinical and microbiologic data and should be treated with antibiotics appropriate for the site and for the susceptibilities of any isolated organisms. Escalation: Patients who remain hemodynamically unstable after initial doses with standard agents for neutropenic fever should have their antimicrobial regimen. De-escalaton: Low-risk patients who have initiated oral antibiotics in the hospital may have their treatment approach simplified if they are clinically stable. Empirical antifungal coverage should be considered in high-risk patients who have persistent fever after 4 7 days of a broad-spectrum antibacterial regimen and no identified fever source. First line: amphotericin B for Candida spp, voriconazole for Aspergillus spp Second line: Caspofungin for Candida spp Please send appropriate sample for culture and sensitivity and de-escalate wherever possible as per the sensitivity. 23

Therapy Duration A. Patient becomes afebrile in 3 days 1. Patient afebrile by day 3. Etiologic agent identified - adjust therapy to most appropriate drugs. No etiologic agent identified : Patient at low risk initially, and on oral antibiotics with no subsequent complications - continue use of the same drugs Patient at low risk initially and therapy with i.v.drugs begun with no subsequent complications change to oral ciprofloxacin + amoxicillin clavulanate after 48 hours. Patient at high risk initially with no subsequent complication continue use of same i.v.drugs B. Persistent fever throughout the first 3 days ANC 500cells /mm 3 for 2 consecutive days, no definite site of infection, and no positive cultures - stop antibiotic therapy when the patient is afebrile for 48 h. ANC < 500 cells /mm 3 Patient initially at low risk, and no subsequent complications -stop therapy when patient is afebrile for 5-7 days Patient initially at risk and no subsequent complications - continue same antibiotics 2. Persistent fever on day 3. Reassess therapy on day 3 If no clinical worsening, continue use ot the same antibiotics. Stop Vancomycin ( if part of initial regimen) if cultures negative If there progressive disease, change antibiotics ( Imipenem 0.5gm i.v.q6h / Meropenem 1gmi.v.Q8H). If patient febrile after 72-96 hours, consider adding Amphotericin B, with and without a change in antibiotic regimen. Additional indications for Amphotericin B /Voriconazole: Pleural rub, pulmonary infiltrates suggestive of invasive aspergillosis, paranasal sinusitis. ANC 500cells /mm 3 - stop antibiotics 4-5 days after ANC 2 500cells /mm 3.- ANC < 500 cells /mm 3 - reassess and continue antibiotics for 2 more weeks; reassess and consider stopping therapy if no disease site found Others Hand hygiene, maximal sterile barrier precautions, and cutaneous antisepsis with chlorhexidine during CVC insertion are recommended for all CVC insertions. Please send appropriate sample for culture and sensitivity and de-escalate wherever possible as per the sensitivity. 24

Notes 25

Seven steps of handwashing Rub palms together. Rub the back of both hands. Interlace fingers and rub hands together. Interlock fingers and rub the back of fingers of both hands Rub thumb in a rotating manner followed by the area between index finger and thumb for both hands. Rub fingertips on palm for both hands. Rub both wrists in a rotating manner. Rinse and dry thoroughly Published by Department of Microbiology, JIPMER

Handbook of Antimicrobial Use at JIPMER POCKET GUIDE For internal use only Valid till July 2013