Making every antibiotic count. Bacterial Meningitis. INDICATION FOR THERAPY USUAL CAUSATIVE ORGANISMS Age y EMPIRIC ANTIBIOTIC REGIMENS

Transcription

1 Bacterial Meningitis INDICATION FOR THERAPY USUAL CAUSATIVE ORGANISMS Age y S. pneumoniae* N. meningitides* H. influenzae* EMPIRIC ANTIBIOTIC REGIMENS Ceftriaxone 2 g IV q12h Vancomycin 20mg/kg x 1 then 15mg/kg q12h Anaphylactic penicillin allergy Age > 50 y or presence of risk factors- alcoholism or altered immune status or pregnancy S. pneumoniae* L. monocytogenes** N. meningitides* ** (eg. Klebsiella or E.coli) Vancomycin 20mg/kg x 1 then 15mg/kg q12h Levofloxacin 750mg IV x 1 then 500mg IV q12h Consult Infectious Diseases Ceftriaxone 2 g IV q12h Vancomycin 20mg/kg x 1 then 15mg/kg q12h Ampicillin 2 g IV q4h Anaphylactic penicillin allergy Vancomycin 20mg/kg x 1 then 15mg/kg q12h Levofloxacin 750mg IV x 1 then 500mg IV q12h Consult Infectious Diseases Consider dexamethasone 0.15 mg/kg IV q6h x 4 days. Initiate dose min before, or with first antibiotic dose but do NOT give if first dose of antibiotics has already been given. Consider discontinuing dexamethasone if meningitis is not caused by S. pneumoniae. Once cultures are available therapy can be tailored * Treatment duration = days, **Treatment duration = 21 days (Group B Strep days) Change ceftriaxone to ceftazidime 2 g IV q8h for patient with a history of neurosurgery or head trauma in last 30 days, a neurosurgical device, or a CSF leak due to high risk of P. aeruginosa and Acinetobacter infections. References: 1. Van de Beek, D; de Gans, J; Tunkel, AR et.al. Community-Acquired Bacterial Meningitis in Adults. NEJM 2006;352: Tunkel, AR, Hartman BJ, Kaplan SL et. al. IDSA Guidelines Practice Guidelines for the Management of Bacterial Meningitis. Clin Infect Dis 2004:39: Updated July 2013

2 Urinary Tract Infections (UTI) INDICATION FOR USUAL CAUSATIVE THERAPY ORGANISMS Uncomplicated Lower tract (acute cystitis/urethritis) (incl. E. coli, Uncomplicated UTIs are Klebsiella, Proteus), defined as symptomatic S. saprophyticus, bacteriuria in adult nonpregnant women with Enterococci apparently normal urinary tracts. Complicated or Catheterassociated Treat catheter-associated bacteruria only if clinical symptoms of urinary tract infection present Upper Tract (mild to moderate pyelonephritis not reguiring hospitalization in women) (incl. E. coli, Klebsiella, Proteus), S. saprophyticus, Enterococci Pseudomonas (incl. Serratia, Enterobacter, Citrobacter), S. saprophyticus, Enterococci ANTIBIOTIC REGIMENS Co-Trimoxazole 1 DS tab PO BID x 3 days Nitrofurantoin (MacroBID) 100 mg PO BID x 5 days Ciprofloxacin 500 mg PO BID x 3 days First Line in Pregnancy: Cephalexin 250 mg PO QID x 7 days Alternatives: Amoxicillin 500 mg PO TID x 7 days (Use only after susceptibility is confirmed) OR Nitrofurantoin (MacroBID) 100 mg PO BID x 7 days* Ceftriaxone 1 g IV q24h x 7 days Ciprofloxacin 500 mg PO BID x 7days** Amoxicillin/Clavulanic Acid 500 mg/125 mg PO TID x 7 days Or Upper Tract (moderate to severe acute pyelonephritis) Therapy can be tailored once causitive organism identified and sensitivities available. Once clinically stable, oral therapy is recommended. (incl. Serratia, Enterobacter, Citrobacter), S. saprophyticus, Enterococci Ciprofloxacin 500mg PO BID x 7 days Ceftriaxone 1g IV q24h x 7 days Ciprofloxacin 400 mg IV q12h x 7 days In Pregnancy: Ceftriaxone 1 g IV q24h x 7 days * There is a theoretical risk of hemolytic anemia in the fetus or newborn, especially in those with G6PD deficiency but cases reports have been rare. Numerous studies have shown the use of nitrofurantoin in pregnancy to be safe (1,3). ** Therapy can be stopped at 3 days in individuals < 60 yrs if catheter removed. These guidelines are for empiric treatment. Therapy should be tapered according to urine culture and sensitivity results once available. Asymptomatic bacteriuria (ASB) routine screening and treatment of ASB is not recommended except in pregnancy and in patients scheduled to undergo TURP or other urologic procedures where mucosal bleeding is expected.

3 References: 1. Nicolle LE, Bradley S, Colgan R, et al. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis 2005;40: Gupta K, Hooton TM, Roberts PL, Stamm WE. Short-Course Nitrofurantoin for the Treatment of Acute Uncomplicated Cystitis in Women. Arch Intern Med. 2007;167(20): Lee M, Bozzo P, Einarson A, et al. Motherisk Update Urinary tract infections in pregnancy. Can Fam Physician 2008;54: Wagenlehmner FME, Weidner W, Naber KG. An update on uncomplicated urinary tract infections in women. Curr Opin Urol 2009;19: Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis 2011;52:e Updated August 2013

4 Staphylococcus aureus bacteremia: Introduction: Staphylococcus aureus is a leading cause of community and hospital-acquired bacteremia. It has a mortality rate of 20-40% with frequent development of complications such as infective endocarditis, epidural abscess and bone/joint infections. Staphylocccus aureus isolated in the blood should NEVER be treated as a contaminant. Treatment requires a minimum of 2 weeks of parenteral antibiotics. Treatment may need to be given parenteral for a minimum 6 weeks in the presence of complications. Treatment should ideally be provided with guidance from Infectious Diseases/Antimicrobial Stewardship Suggested Algorithim: S. aureus bacteremia Vancomycin 20mg/kg IV x 1 then 15mg/kg IV q 12h* Cloxacillin 2g IV q4h or Ancef 2g IV q 8h Methicillin Sensitive S. Aureus (MSSA) Clinical evaluation for complications /- Transesophageal Echocardiogram Ψ Continue Vancomycin Methicillin Resistant S. Aureus (MRSA) *Assumes normal renal function. Refer to Vancomycin dosing guidelines for dosing in renal dysfunction Ψ A TEE is recommended in most patients. Rarely patients can be treated with 2 weeks of antimicrobials without a TEE if they meet the following criteria: Removable focus No predisposing valvular lesions or vegetation seen on Transthoracic Echocardiogram (TTE) No indwelling devices No clinical evidence of complications of S. aureus bacteremia Clinical improvement with repeat blood cultures negative at 72hrs β Six weeks of therapy is adequate for the majority of S. aureus bacteremia complications. Epidural abscesses and osteomyelitis may require a longer duration of therapy. TEE demonstrates endocarditis or complications present TEE does not demonstrate endocarditis and no complications present Consider ID consultation 6 weeks IV Cloxacillin or Ancef β 2 weeks of IV Vancomycin

5 References 1. Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, Kaplan SL, Karchmer AW, Levine DP, Murray BE, J Rybak M, Talan DA, Chambers HF. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52(3):e Lowy FD. Staphylococcus aureus infections. N Engl J Med. 1998;339(8):520. Updated August 2013

6 Skin & Soft Tissue Infections INDICATION FOR THERAPY Uncomplicated Cellulitis, Impetigo, Erysipelas Or Superficial Ulcers with Cellulitis in Non-Diabetic patients Necrotizing Fasciitis* If MRSA suspected add Vancomycin Diabetic foot infection OR Decubitus ulcer (infected) If MRSA suspected add Vancomycin USUAL CAUSATIVE ORGANISMS Group A, C, G Streptococcus, S. aureus MRSA suspected Invasive Group A Streptococcus Mixed aerobic Gramnegative bacilli and anaerobes Most mild superficial infections are: S. aureus Streptococcus species More complicated infections may include: S. aureus Streptococcus species Anaerobes ANTIBIOTIC REGIMENS Cephalexin 500 mg PO QID Cloxacillin 500 mg PO QID Cefazolin 1 g IV q8h Cloxacillin 1-2 g IV q4-6h Septra DS T PO BID Or Vancomycin (dose as per hospital guidelines) Co-trimoxazole 1 DS PO BID Doxycycline 100 mg PO BID Vancomycin (dosing as per hospital guidelines) Penicillin G 4 MU IV q4h Clindamycin 900 mg IV q8h /- IVIG 1-2g/kg x 1, then 0.5-2g/kg at day 2-5 if needed(if signs of Streptococcal Toxic Shock Syndrome). Vancomycin (dose as per hospital guidelines) Clindamycin 900 mg IV q8h /- IVIG 1-2g/kg x 1, then 0.5-2g/kg at day 2-5 if needed(if signs of Streptococcal Toxic Shock Syndrome). Piperacillin/Tazobactam g IV q6h Ceftriaxone 1-2 g IV q24h Clindamycin 900 mg IV q8h Or Metronidazole 500 mg IV BID MILD Infection: Superficial, Localized with no Systemic Involvement Cephalexin 500 mg PO QID Amoxicillin/Clavulanic Acid 500 mg/125 mg PO TID Co-trimoxazole 1 DS tab PO BID Metronidazole 500 mg PO BID Cefazolin 1 g IV q8h MODERATE Infection: full thickness ulcer with deep tissue involvement, NO systemic illness Ceftriaxone 1 g IV q24h Metronidazole 500 mg PO/IV q12h Amoxicillin/Clavulanic Acid 500 mg/125 mg PO TID Levofloxacin 750 PO/IV q24h Metronidazole 500 mg PO/IV q12h SEVERE Infection: Systemic or Bone Involvement** Piperacillin/Tazobactam g IV q6h Ceftriaxone 1 g IV q24h Metronidazole 500 mg PO/IV q12h Levofloxacin 750 PO/IV q24h Metronidazole 500 mg PO/IV q12h

7 Cellulitis/Phlebitis secondary to IV line Majority of cases can be treated with catheter removal and warm compress TID alone Human Bites** Give tetanus booster (Td) if none in the past 5 years. Animal Bites (Dogs and Cats) Give tetanus booster (Td) if none in the past 5 years. S. aureus Coagulase-negative staphylococci (including S. epidermidis) S. aureus Streptococcus species Oral anaerobes Haemophilus species Eikenella corrodens S. aureus Streptococcus species Oral anaerobes Pasteurella multocida Captnocytophaga canimorsus If antibiotics required: Cefazolin 1 g IV q8h Penicillin Anaphylaxis or MRSA Suspected: Vancomycin (dose as per hospital guidelines) Non-Severe Infections: Amoxicillin-Clavulanic Acid 500/125 mg PO TID Severe infections: Ceftriaxone 1 g IV q24h Metronidazole 500 mg PO/IV q12h Piperacillin/Tazobactam g IV q6h Clindamycin 300 mg PO QID one of: Co-trimoxazole 2 DS PO BID Or Levofloxacin 750 PO/IV q24h Or Doxycycline 100 mg PO BID Prophylaxis***: Amoxicillin-Clavulanic Acid 500mg/125 mg PO TID x 3-5 days Treatment Non-Severe: Amoxicillin-Clavulanic Acid 500/125 mg PO TID Treatment Severe: Ceftriaxone 1 g IV q24h Metronidazole 500 mg PO/IV q12h Piperacillin/Tazobactam g IV q6h Clindamycin 300 mg PO QID one of: Co-trimoxazole 2 DS PO BID Or Levofloxacin 750mg IV/PO q24h Or Doxycycline 100 mg PO BID Note: Most cases of uncomplicated cellulitis can be managed using oral therapy alone. If intravenous therapy is needed initially (inability to take oral medications or early concern regarding aggressive infection), step-down to oral antibiotics should be considered within hours. A total duration of therapy of 5-7 days is sufficient for most uncomplicated skin and soft tissue infections. *Severe soft tissue infections may require a combined medical and surgical approach. ** Human bites do not generally require prophylaxis, but can be considered if the wound is through the dermis, especially on the hand. *** Consider prophylaxis for animal bites if: 1. moderate to severe injury <8 hours old, especially if edema or crush injury; 2. deep puncture wounds (especially due to cat bites); 3. hand wounds or in close proximity to a bone or joint (particularly prosthetic joints); 4. immunocompromised patients (including those with splenectomy, liver disease, or steroid therapy); 5. wounds requiring closure; and 6. wound is in the genital area.

8 References: (1) Stevens DL, Bisno AL, Chambers HF et al. Guidelines for Skin and Soft-Tissue Infections. Clin Infect Dis 2005;41: (2) Mermel LA, Farr BM, Sherertz RJ et al. Guidelines for the Management of Intravascular Catheter- Related Infections. Clin Infect Dis 2001;32: (3) Lipsky BA, Berendt AR, Cornia PB, Pile JC et al. Diagnosis and Treatment of Diabetic Foot Infections. Clin Infect Dis 2012;54: Updated August 2013

9 Pelvic Inflammatory Disease INDICATION FOR THERAPY Ambulatory-outpatient USUAL CAUSATIVE ORGANISMS Chlamydia N. gonorrhoeae Anaerobes ANTIBIOTIC REGIMENS Ceftriaxone 250 mg IM x 1 Doxycycline 100 mg PO q12h x 14 days /- Metronidazole 500 mg PO q12h x 14 days Severe -Requiring Hospitalization Chlamydia N. gonorrhoeae Anaerobes Cefixime 800 mg PO x 1 dose Doxycycline 100 mg PO bid x 14 days Cefoxitin 2g IV q6h* Doxycycline 100 mg PO BID Ceftriaxone* 1 g IV q24h Metronidazole* 500 mg IV/PO q12h Doxycycline 100 mg PO q12h Clindamycin* 900 mg IV q8h Gentamicin (as per hospital guidelines)* Metronidazole should be added if a tuboovarian abscess is suspected *When patient clinically improved, step down to oral antibiotics therapy with Doxycycline 100 mg po BID or Clindamycin 450 mg po QID or Amoxicillin Clavulanic acid 875/125 mg PO BID (Clindamycin or Amoxicillin Clavulanic acid preferred if tuboovarian abscess suspected) x 14 days total Reference: 1. Canadian Guidelines on Sexually Transmitted Infections, January 2010 Edition. Ottawa, ON: Public Health Agency of Canada, Availabile from: URL: 2. Public Health Agency of Canada update on the Treatment of Gonococcal Infections Updated Aug 2013

10 Intra-abdominal Infections INDICATION FOR THERAPY Community Acquired Uncomplicated (Non-perforated appendicitis, perforations without established infection) USUAL CAUSATIVE ORGANISMS Anaerobes /- Gram-positive cocci (stomach/duodenum) ANTIBIOTIC REGIMENS Cefazolin 1 g IV q8h Metronidazole 500 mg IV q12h Penicillin anaphylaxis: Gentamicin 5mg/kg IV x 1 dose then pharmacy to dose Metronidazole 500 mg IV/PO q12h Community Acquired Complicated Mild to moderate infections (perforated appendicitis, diverticulitis) Anaerobes (including B. fragilis) Cefazolin 1 g IV q8h Metronidazole 500 mg IV q12h Penicillin anaphylaxis: Gentamicin 5mg/kg IV x 1 dose then pharmacy to dose Metronidazole 500 mg IV/PO q12h Community Acquired Complicated Same as above Ceftriaxone 1g IV q24h Metronidazole 500 mg IV/PO q12h Severe infections (Shock, new organ failure, ICU patient) Health Care Associated Mild to moderate infections (Hospitalized 5 days, anastomotic leak, postoperative abscess, recent antibiotics, recent hospitalization) Health Care Associated Severe infections (Hospitalized 5 days, anastomotic leak, shock, ICU, recent antibiotics, recent hospitalization) Anaerobes Enterococcus Possibly drug resistant gram negative bacilli Anaerobes Enterococcus Possibly drug resistant gram negative bacilli Piperacillin-tazobactam g IV q6h Gentamicin 5mg/kg IV x 1 dose then pharmacy to dose Metronidazole 500 mg IV/PO q12h Ceftriaxone 1g IV q24h Metronidazole 500 mg IV/PO q12h Piperacilin-tazobactam g IV q6h Vancomycin 20mg/kg IV x 1 then 15mg/kg IV q12h Gentamicin 5mg/kg IV x 1 dose then pharmacy to dose Metronidazole 500 mg IV/PO q12h Piperacilin-tazobactam g IV q6h Vancomycin 20mg/kg IV x 1 then 15mg/kg IV q12h Gentamicin 5mg/kg IV x 1 dose then pharmacy to dose Metronidazole 500 mg IV/PO q12h Penicillin Allergy (non-anaphylaxis): Meropenem 1 g IV q8h

11 Biliary Tract (e.g. acute cholangitis) Mild to moderate Biliary Tract Severe Enterococcus, Streptococci,, Anaerobes Enterococcus, Streptococci,, Anaerobes Cefazolin 1 g IV q8h Ceftriaxone 1 g IV q24h Gentamicin (as per hospital guidelines) Ceftriaxone 1 g IV q24h Ampicillin 2 g IV q6h Flagyl 500mg IV/PO q12h Piperacillin-tazobactam g IV q6h Prophylaxis for Spontaneous Bacterial Peritonitis S. pneumoniae Streptococcus sp. Vancomycin (dose as per hospital guidelines) Gentamicin (dose as per hospital guidelines) Short term (e.g. GI Bleed) Co-trimoxazole 1 DS PO bid x 7 days Long term (e.g.previous episode of SBP or ascitic fluid protein < 10 g/l) Co-trimoxazole 1 DS tab PO daily or Ciprofloxacin 500 mg PO daily Note: After source control is complete and there is resolution of clinical signs of infection (normalization of WBC count and absence of fever), antimicrobials can be discontinued. This is usually 3-7 days of antimicrobials following source control. References: 1. Solomkin J, et al. Diagnosis and management of complicated intra-abdominal infections in adults and children: guidelines by the Surgical Infection Society and the Infections Diseases Society of America. Clin Infect Dis 2010;50: Antibiotics for complicated intra-abdominal infections. Pharmacist s Letter/Prescriber s Letter 2010;26(3): Toronto Antimicrobial Stewardship Corridor (TASC). Best Practice in General Surgery: Management of Intra-Abdominal Infections, Dec Updated August 2013

12 Infective Endocarditis (IE) INDICATION FOR USUAL CAUSATIVE THERAPY ORGANISMS Streptococcal Viridans group streptococci (S Endocarditis sanguis, S mitis, S salivarius, S mutans) (Penicillin susceptible Streptococcus bovis strains) ANTIBIOTIC REGIMENS Native Valve Penicillin G sodium MU IV divided q4-6h x 4-6 weeks Ceftriaxone 2 g IV/IM q24h x 4-6 weeks Combination Therapy for shorter treatment duration (only with ID consultation) Penicillin G sodium MU IV divided q4-6h x 2 weeks Gentamicin* 1 mg/kg IV q8h x 2 weeks Combination Therapy for shorter treatment duration (only with ID consultation) Ceftriaxone 2 g IV/IM q24h x 2 weeks Gentamicin* 1 mg/kg IV q8h x 2 weeks Vancomycin** x 4 weeks Prosthetic Valve Penicillin G sodium 24 MU IV divided q4-6h x 6 weeks May consider adding: Gentamicin* 1 mg/kg IV q8h x 2 weeks Ceftriaxone 2 g IV/IM q24h x 6 weeks May consider adding: Gentamicin* 1 mg/kg IV q8h x 2 weeks Staphylococcal Endocarditis S aureus (MSSA) Vancomycin** x 6 weeks Native Valve Cloxacillin 2 g IV q4h x 6 weeks May consider adding: Gentamicin* 1 mg/kg IV q8h x 3-5 days Cefazolin 2 g IV q8h x 6 weeks May consider adding: Gentamicin* 1 mg/kg IV q8h x 3-5 days

13 Vancomycin** x 6 weeks Prosthetic Valve Cloxacillin 2 g IV q4h x 6 weeks Rifampin 300 mg po q8h x 6 weeks Gentamicin* 1 mg/kg IV q8h x 2 weeks Enterococcal Endocarditis (penicillin, gentamicin and vancomycin susceptible strains) E faecalis E faecium Vancomycin** x 6 weeks Rifampin 300 mg po q8h x 6 weeks Gentamicin* 1 mg/kg IV q8h x 2 weeks Native Valve Ampicillin 2 g IV q4h x 4 weeks*** Gentamicin* 1 mg/kg IV q8h x 4 weeks Penicillin G sodium MU IV divided q4h x 4 weeks*** Gentamicin* 1 mg/kg IV q8h x 4 weeks Vancomycin** x 6 weeks Gentamicin* 1 mg/kg IV q8h x 6 weeks Prosthetic Valve Ampicillin 2 g IV q4h x 6 weeks Gentamicin* 1 mg/kg IV q8h x 6 weeks Penicillin G sodium MU IV divided q4h x 6 weeks Gentamicin* 1 mg/kg IV q8h x 6 weeks Endocarditis other pathogens Coagulase-negative staphylococcus MRSA Enterococcus (drug resistant) HACEK microorganisms Culture-Negative Fungi Vancomycin** x 6 weeks Gentamicin* 1 mg/kg IV q8h x 6 weeks Consult with Infectious Diseases service

14 Empiric treatment of IE is not recommended. A microbiologic diagnosis should be aggressively sought before therapy is started. Please consider consultation with Infectious Diseases service if empiric therapy is being considered. *There is insufficient data for the use of high dose (once-daily) aminoglycosides in the treatment of IE. Target peak 3-4 mg/l, trough < 1 mg/l. Addition of gentamicin in IE caused by staphylococci in absence of prosthetic material is optional as clinical benefit of this practice has not been established. **Vancomycin - dose as per hospital guidelines. Target trough mg/l. ***Treat x 6 weeks if patient has had symptoms of illness for greater than 3 months. References: 1. AHA Scientific Statement. Infective Endocarditis: Diagnosis, Antimicrobial Therapy and Management of Complications. Circulation 2005:11:e394-e Ribera E, Gomez-Jimenez J, Cortes E et al. Effectiveness of cloxacillin with and without gentamicin in short-term therapy for right-sided Staphylococcus aureus endocarditis: a randomized, controlled trial. Ann Intern Med 1996:125: Updated July 2013

15 Hospital Acquired Pneumonia (HAP) & Ventilator Associated Pneumonia (VAP) INDICATION FOR THERAPY HAP or VAP with early onset (occurring within 4 days of hospitalization) and: No previous antibiotics in last 3 months; No recent hospitalization lasting > 5 days; No immunosuppressive disease USUAL CAUSATIVE ORGANISMS Streptococcus pneumoniae Haemophilus influenzae Methicillin-sensitive S.aureus Enteric gram negative bacilli (E.Coli, K. pneumoniae, Enterobacter sp, Proteus sp, Serratia marcescens) ANTIBIOTIC REGIMENS Ceftriaxone 1g IV q24h /- Azithromycin 500 mg IV q24h then Azithromycin 250 mg IV q24h x 4 days If B-lactam anaphylactic allergy or life threatening reaction: Levofloxacin 750 mg IV/PO q24h HAP of late onset (>4 days of hospitalization) and: No immunosuppressive disease; Hemodynamically stable; No previous antibiotics in last 3 months; No bronchiectasis; Not intubated Enteric gram-negative bacilli (Klebsiella, Enterobacter, Serratia, E. coli, Proteus, Haemophilus influenzae, Pseudomonas) and Staphylococcus aureus Note: Pseudomonas is an infrequent cause of pneumonia in non-critical care areas at TEGH. Ceftriaxone 1g IV q24h If B-lactam anaphylactic allergy or life threatening reaction: Levofloxacin 750 mg IV/PO q24h HAP or VAP Late onset (occurring after 5 days of hospitalization) with: Previous antibiotics in last 3 months, or Recent hospitalization > 5 days, or Immunosuppressive disease or therapy Pathogens listed above plus the following pathogens that have the potential for multi-drug resistance: Pseudomonas aeruginosa Klebsiella pneumoniae Acinetobacter sp. Piperacillin-tazobactam 4.5 g IV q6h Penicillin Allergy: (if no history of anaphylaxis) Meropenem 1 g IV q8h If B-lactam anaphylactic allergy or life threatening reaction: Vancomycin 15mg/kg IV q12h Ciprofloxacin 400mg IV q12h /- Gentamicin (see dosing guidelines) *Consider ID/ASP consult

16 HAP or VAP with MRSA suspected Methicillin Resistant Staphylococcus aureus (MRSA) (risk factors include MRSA colonization, head trauma, diabetes, hospitalization in ICU) Add Vancomycin 15mg/kg IV q12h Hospital Acquired Pneumonia (HAP) - pneumonia that occurs >48 after hospital admission, which was not incubating at the time of admission. Ventilator Associated Pneumonia (VAP) - pneumonia that arises > h after endotracheal intubation. Duration of Treatment: Patients initially treated with appropriate antibiotics may only require 7-8 days of total therapy with the exception of P.aeruginosa pneumonia which may require a longer duration of treatment. Combination regimens of beta-lactam-aminoglycoside combinations to treat P. aeruginosa infections are not routinely recommended due to the lack of documented clear benefit. Combination therapy should be considered in specific patient circumstances such as previous infection with multi-drug resistant P.aeruginosa, febrile neutropenia etc. References: 1. American Thoracic Society/ Infectious Diseases Society of America. Guidelines for the Management of Adults with Hospital-Acquired, Ventilator-Associated and Healthcare-Associated Pneumonia. Am J Respir Crit Care Med 2005;171: Chastre J, Wolff M, Fagon JY et al. Comparison of 8 vs. 15 Days of Antibiotic Therapy for Ventilator-Associated Pneumonia in Adults. JAMA 2003;90: Hilf M, Yu VL, Sharp J et al. Antibiotic therapy for Pseudomonas aeruginosa bacteremia: outcome correlations in a prospective study of 200 patients. Am J Med 1989;87: Rotstein C, Evans G, Born A, et al. Clinical practice guidelines for hospital-acquired pneumonia and ventilator-associated pneumonia in adults. Can J Infect Dis Med Microbiol 2008;19(1): Updated July 2013

17 Community Acquired Pneumonia (CAP) INDICATION FOR THERAPY Outpatient Treatment Individual with comorbidites (chronic heart, lung, liver or renal disease, diabetes, alcoholism, malignancies, asplenia) Individuals with immunosuppressive disease or on immunosuppressant therapy Use of antibiotics in last 3 months (consider selecting an antibiotic from a different class as previous exposure to antibiotics within this timeframe is a risk factor for developing drug-resistant streptococcus pneumoniae) Inpatient admission (Non-ICU) USUAL CAUSATIVE ORGANISMS S. pneumoniae M. pneumoniae C. pneumoniae H. influenzae M. cattharalis Legionella sp. S. pneumoniae M. pneumoniae C. pneumoniae H. influenzae Legionella sp. ANTIBIOTIC REGIMENS Amoxicillin-clavulanate 500/125 mg PO tid /- Azithromycin 500 mg PO day 1, then 250 mg PO daily x 4 days If B-lactam anaphylactic allergy or life threatening reaction: Levofloxacin 750 mg PO daily Ceftriaxone 1 g IV q24h Azithromycin 500 mg IV/PO day 1, then mg IV/PO q24h x 4 days If B-lactam anaphylactic allergy: Levofloxacin 750 mg IV/PO q24h Inpatient ICU admission S. pneumoniae S. aureus Legionella sp. Gram negative bacilli H. influenzae Options for oral step-down therapy from ceftriaxone include: Amoxicillin/clavulanate 500/125 mg PO TID or Cefuroxime 500 mg PO BID Ceftriaxone 1 g IV q24h Azithromycin 500 mg IV q24h If B-lactam anaphylactic allergy: Levofloxacin 750 mg IV q24h Add Oseltamavir 75 mg PO q12h x 5 days Influenza suspected Influenza A or B (symptoms for < 48 h) Macroaspiration suspected Oral Anaerobes Ceftriaxone 1g IV q24h (CTX has adequate oral anaerobic coverage and may be used alone.) In the setting of severe anaerobic pulmonary infection (e.g. lung abscess, empyema) Metronidazole 500 mg IV/PO q12h may be added. Amoxicillin/clavulanate 500/125 mg PO TID

18 MRSA suspected MRSA Add Vancomycin 15mg/kg IV q12h (Dose as per hospital guidelines) Pseudomonas suspected Pseudomonas Refer to Hospital Acquired Pneumonia Guidelines If the patient has received antibiotics within the last 3 months consideration should be given to prescribing an agent from a different class. Duration of therapy: minimum of 5 days. Patients should be afebrile for 48h and clinically stable before discontinuation of therapy. References: 1. Mandell LA, Wunderink RG, Anzueto A et al. Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clin Infect Dis 2007;44:S Ruhe JJ, Hasbun R. Streptococcus pneumoniae Bacteremia: Duration and Previous Antibiotic Use and Association with Penicillin Resistance. Clin Infect Dis 2003;36: Leroy O, Saux P, Bedos JP, Caulin E. Comparison of Levofloxacin and Cefotaxime Combined With Ofloxacin for ICU Patients With Community-Acquired Pneumonia Who Do Not Require Vasopressors. CHEST 2005;128: Doernberg SB, Winston LG, Deck DH, Chambers HF. Does doxycycline protect against development of Clostridium difficile Infection? Clin Infect Dis 2012:55: El Moussaoui R, De Borgie CAMJ, Van Den Broek P, et al. (2006). Effectiveness of discontinuing antibiotic treatment after three days versus eight days in mild to moderate-severe community acquired pneumonia: randomised, double blind study. BMJ British Medical Journal, 332(7554), Updated July 2013

19 Clostridium Difficile Associated Diarrhea INDICATION FOR THERAPY CLINICAL CRITERIA ANTIBIOTIC REGIMENS Mild to moderate WBC < 15 SrCr < 1.5 times baseline Metronidazole 500 mg PO TID x 10 days then reassess If patient is unable to take oral medications*: Metronidazole 500 mg IV q8h x 10 days then reassess Severe Uncomplicated Disease WBC > 15 SrCr > 1.5 times baseline Vancomycin 125 mg PO QID* x days Severe Complicated Disease WBC > 15 SrCr > 1.5 times baseline Hypotension or shock Ileus Toxic megacolon or perforation Vancomycin 500mg PO/NG QID* Note if complete ileus PR administration of Vancomycin should be considered** Metronidazole 500 mg IV TID x 14 days then reassess *Note: Intravenous vancomycin is not effective for CDAD treatment **Vancomycin 500mg PR syringe QID instilled for 2-.3hr or as long as patient can tolerate (caution with toxic megacolon) Management of all cases should include: Discontinue inciting antibiotics, when possible. Do not start new exacerbating antibiotics, when possible. Avoid motility and antimotility agents, opioids, stool softeners, laxatives, proton pump inhibitors. Review hydration status. Treatment of Recurrent Disease: Consider Infectious Diseases consultation. Outpatient treatment with oral vancomycin is very expensive; however, treatment may be covered under the Ontario Drug Benefit Exceptional Access Program for selected patients. EAP coverage can be obtained through the Telephone Request Service Reference: Cohen et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults: 2010 Update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infection Control and Hospital Epidemiology. 2010:31: Updated July 2013

20 Candidemia/Invasive Candidiasis INDICATION FOR THERAPY Non-neutropenic adult CAUSATIVE ORGANISMS Empiric Treatment ANTIBIOTIC REGIMENS Fluconazole 800 mg IV load, then 400 mg q24h Caspofungin 70 mg IV load, then 50 mg IV q24h Neutropenic adult with Empiric Treatment* persistent, unexplained fever despite 4-7days of appropriate antibiotic therapy Amphotericin B mg/kg IV q24h Caspofungin 70 mg IV load, then 50 mg IV daily Amphotericin B mg/kg IV q24h Initial therapy when Candida species has been identified (Note: therapy can be further tailored once sensitivitiess are available) C. albicans C. tropicalis C. parapsilosis C. glabrata Fluconazole 400 mg IV/ /PO q24h Caspofungin 70 mg IV load, then 50 mg IV q24h Note: Therapy may be changed to Fluconazole 4000 mg IV/PO q24h if fluconazole sensitivity has been demonstrated by in-vitro testing. C. krusei Caspofungin 70 mg IV load, C. krusei is intrinsically resistant then 50 mg IV q24h to fluconazole C. lusitaniae Fluconazole 400 mg IV/ /PO q24h Amphotericin B resistance has been well documentedd for many isolatess *Fluconazole not routinely used in neutropenic individuals as this drug does not cover filamentous fungi or fluconazole-resistant Candida. Duration of therapy: 14 days after the last positive blood culture, no metastatic complications and resolution of signs and symptoms of infection. NHS Specific Data: There were 80 episodes of candidemia from 2008 to July 1, The most common isolates were C. albicans (45%), C. parapsilosiss (23.75%) and C. glabrata (13.75%). Of the 11 C. glabrata isolates none of them weree resistant to fluconazole.

21 Lipid formulations of amphotericin B: ( mg/kg/day) may bee considered if the patient meets one of the following criteria: 1) Initial renal insufficiency (creatinine clearance < 25 ml/min or serum creatinine > 220 umol/ /L). 2) Significant increase in creatinine while on conventional amphotericin B (up to 220 umol/l). 3) Severe, acute administration related toxicity despite pre-medication. 4) Disease progression after > 500mg of conventional amphotericin. References: 1. Blondel-Hill E, Fryters S, editors. Bugs and Drugs. Edmonton: Capital Health; Dismukes WE. Introduction to Antifungal Drugs. Clin Infect Dis 2000;30: Pappas PG, Rex JH, Sobe JD et al. Clinical Practice Guidelines for the Management of Candidiasis: 2009 Update by the Infectious Diseases Society of America. Clinn Infect Dis 2009;48: Updated August 2013