Restricted Anti-infective Indications HNEH CG 10_06 CLINICAL PRACTICE GUIDELINE Restricted Anti-infective Indications Document Registration Number HNEH CG 10_06 Sites where CPG applies Acute Networks Hospitals Primary & Community Networks Target Clinical Audience Clinicians who prescribe restricted anti-infectives Pharmacists Applicability Neonate – less than 29 days *NB: *Please be aware that young Children up to 16 years* people between 16 and 18 years of Adult (18 years and over) age may have a number of other All of the above guideline, policy or legal requirements that should be adhered to but for the purposes of guideline development can be considered adult □ √ √ □ Summary This document describes accepted indications for restricted anti-infectives as defined by the HNE Health Area Antiinfective Working Party. Keywords Restricted antibiotics, antibiotic stewardship, patient safety Replaces existing clinical practice guideline or policy? Yes Registration Numbers of Superseded Documents HNEH CPG 08_04 from 6 March 2008 HNEH CPG 09_12 from 26 November 2009 Related documents (Policies, Australian Standards, Codes of Conduct, legislation etc) • Therapeutic Guidelines: Antibiotic, Therapeutic Guidelines, Melbourne, Victoria 2006 Clinical Network/stream leader responsible for CPG Dr John Ferguson, Area Director Infection Prevention and Control Contact Person/Position Responsible Dr John Ferguson, Area Director Infection Prevention and Control Contact Details John.Ferguson@hnehealth.nsw.gov.au Ph: 4921 4444 Issue Date: 14 September 2010 Review Due Date: July 2013 Date authorised by Expert Working Group/s Area Quality Use of Medicines Committee - February 2009 Date noted by HNE Health Clinical Quality and Patient Safety Committee 9 September 2010 Trim Number 10/26-1-10 Version Two Anti-infective Working Group - June 2010 September 2010 Restricted Anti-infective Indications HNEH CG 10_06 GLOSSARY Listed of acronyms and terms with their definitions Acronym or Term Definition MRSA Methicillin-Resistant Staphylococcus aureus VRE Vancomycin-Resistant enterococci C. difficile Clostridium difficile, the important bacterial cause of post antibiotic colitis/enteritis IV Intravenous IM Intramuscular PO Per-oral Section 100 (S100) Section 100 of the Highly Specialised Drugs (HSD) Program Guidance DS registration Provides for close analysis of restricted anti-infective prescriptions and use with timely feedback to prescribers mg/kg Milligrams per kilogram in weight of child CORB Severity score for adults with community-acquired pneumonia. Confusion, Oxygenation, Respiratory Rate and Blood Pressure See HNE Health community-acquired pneumonia Clinical Practice Guideline. 2 g 8-hrly 2 grams every 8 hours S. aureus Staphylococcus aureus JHH John Hunter Hospital MAC Mycobacterium avium Complex Haemophilus influenzae Type b (Hib) Bacterial infection associated with meningitis and epiglottitis TG Therapeutic Guidelines CF Cystic Fibrosis AUC Area Under the Curve Version One September 2010 Page 2 Restricted Anti-infective Indications HNEH CG 10_06 GUIDELINE Antimicrobial exposure is associated with the emergence and spread of antibiotic resistant organisms such as Methicillin-Resistant Staphylococcus aureus (MRSA), Vancomycin-Resistant enterococci (VRE) and multi-resistant Gram negative bacteria. Furthermore, Clostridium difficile infections may also be caused through antibiotic treatment. The existence of hypervirulent epidemic strains of C. difficile internationally further increases the importance of reducing antimicrobial use. 3 levels of anti-infective restriction exist: 1. Unrestricted anti-infectives (‘Category A’) 2. Restricted anti-infectives with approved indications (‘Category B’) 3. Anti-infectives requiring Infectious Diseases Approval (‘Category C’) Summary of antibiotics: (Shaded agents require registration with Guidance DS) Category A Category B Class (see Appendix 1) Amoxycillin Amikacin Antibiotics Amoxycillin/clavulanate Azithromycin (IV/PO) Ampicillin Aztreonam Benzylpenicillin Cefepime Cefaclor Ceftazidime Cefuroxime Cefotaxime Cephalexin Ceftriaxone Cephazolin Ciprofloxacin (IV/PO) Clarithromycin Clindamycin (PO) Colistin (Inhaled) Fusidic acid Dicloxacillin (PO) Lincomycin (IV) Meropenem (for CF and Doxycycline bronchiectasis) Erythromycin (IV/PO) Flucloxacillin (IV/PO susp) Norfloxacin Gentamicin Piperacillin/tazobactam Griseofulvin Rifabutin** Metronidazole (IV/PO) Rifampicin Neomycin Vancomycin (IV) Nitrofurantoin Vancomycin (PO) Phenoxymethylpenicillin Roxithromycin Sulfamethoxazole/ Trimethoprim (IV/PO) Tobramycin (IV/Inhaled) Trimethoprim Amphotericin lozenge Antifungals Fluconazole (IV/PO) Itraconazole Ketoconazole Terbinafine Tinidazole Aciclovir (IV/PO) Ganciclovir Antivirals Oseltamivir Famciclovir Ribavirin** Valaciclovir Antiprotozoals Antimycobacterials Category C Colistin IV Flucytosine Meropenem* Moxifloxacin (IV/PO) Teicoplanin Tigecycline Linezolid Amphotericin (IV) Caspofungin Posaconazole Voriconazole (IV/PO) Foscarnet Cidofovir Valganciclovir** Artemether/lumefantrine Artesunate Primaquine Dapsone Ethambutol Isoniazid Pyrazinamide Albendazole Ivermectin Praziquantel Antihelminthics * See page 3 and 4 for meropenem exemptions ** Unless Section 100 (S100) criteria met Version One September 2010 Page 3 Restricted Anti-infective Indications HNEH CG 10_06 Appendix 1: Category B Drugs Agents requiring Guidance DS registration at JHH are shaded in grey. For other proposed indications at JHH discussion with Infectious Diseases Registrar (page: 5630) or on-call Infectious Diseases Specialist is suggested (via 4921 3000). Restricted Antibiotic Amikacin (IV) (See TG: Antibiotic for dosing) Azithromycin (IV/oral) Adult: 500 mg daily Child: 10 mg/kg up to 500 mg daily SWITCH TO ORAL AS SOON AS PRACTICABLE Aztreonam (IV) Adult: 2 g IV 8-hrly, Child > 2 yrs: 50 mg/kg up to 2 g IV 8-hrly Cefepime (IV) Adult: 2 g IV 8-hrly Child: 50 mg/kg up to 2 g IV 8-hrly Cefotaxime (IV) Non-meningeal infections: Adult: 1 g IV 8-hrly Child: 25 mg/kg up to 1 g IV 8-hrly Ceftazidime (IV) Adult: 2 g IV 8-hrly Child: 50 mg/kg up to 2 g IV 8-hrly Ceftriaxone (IV) Non-meningeal infections: Adult: 1 g IV daily Child: 25 mg/kg up to 1 g IV daily (Meningeal infections consult Infectious Diseases) Accepted Indications and Comments - Adult or paediatric respiratory patients – reserved for tobramycin-resistant Pseudomonas - - - Cystic fibrosis acute exacerbation Adult or paediatric respiratory patients – proven pseudomonal infection (same dose usually together with once daily aminoglycoside) - Child with proven or suspected bacterial meningitis (use 50 mg/kg up to 2 g IV 6-hrly) Ongoing second line for child with severe pneumonia (if significant renal failure or minor penicillin allergy present) - - Ciprofloxacin (IV/oral) Adult: Oral: 500 mg 12-hrly IV: 400 mg 12-hrly SWITCH TO ORAL AS SOON AS PRACTICABLE Version One Severe community-acquired pneumonia (with CORB> 2) Urethritis, cervicitis or conjunctivitis due to Chlamydia trachomatis (Adult: 1 g oral as a single dose; child: 20 mg/kg up to 1 g oral as a single dose) Sexually acquired pelvic inflammatory disease (1 g single oral dose). Should be used with ceftriaxone 500 mg IM/IV, oral doxycycline 100 mg 12-hrly and oral metronidazole 400 mg 12-hrly Cystic fibrosis acute exacerbation - Cystic fibrosis respiratory exacerbation; especially infections due to Burkholderia cepacia Adult or paediatric respiratory patients – proven pseudomonal infection (same dose usually together with once daily aminoglycoside) Febrile neutropenia with a minor penicillin allergy Proven or suspected bacterial meningitis (use 50 mg/kg up to 2 g IV 12-hrly) Severe community acquired pneumonia (CORB≥2 and presence of significant renal failure or minor penicillin allergy) Spontaneous bacterial peritonitis Pelvic inflammatory disease - sexually acquired (use with oral metronidazole 400 mg 12-hrly, oral doxycycline 100 mg 12-hrly and oral azithromycin 1 g as a single dose) Disseminated gonococcal infection Neisseria meningitides prophylaxis (second line) All orbital (postseptal) or severe periorbital (preseptal) cellulitis (50 mg/kg up to 2 g IV once daily) Bites and clenched fist injuries with established infection (with metronidazole) Patients with bronchiectasis where ciprofloxacin sensitive Pseudomonas aeurginosa is isolated Salmonella enteritis Pyelonephritis - proven gram negative organism resistant to narrower spectrum agents, or patient unable to tolerate narrower spectrum antibiotics due to allergy etc Chronic prostatitis Cellulitis after a water related injury Diabetic foot infection September 2010 Page 4 Restricted Antibiotic Clindamycin (oral) Adult: 450 mg orally 8-hrly Child: 10 mg/kg up to 450 mg 8-hrly Fusidic acid (oral) Adult: 500 mg 12-hrly Ganciclovir (IV) (see TG: Antibiotic for dosing) Lincomycin (IV) Aerobic infection: Adult: 600 mg IV 8-hrly Child: 15 mg/kg up to 600 mg IV 8-hrly Anaerobic infection: Adult: 900 mg IV 8-hrly Child: 15 mg/kg up to 900 mg IV 8-hrly Meropenem (IV) Cystic fibrosis: Adult: 2 g IV 8-hrly Child: 50 mg/kg up to 2 g IV 8-hrly Restricted Anti-infective Indications HNEH CG 10_06 Accepted Indications and Comments Intravenous clindamycin is no longer stocked by John Hunter Hospital. Please see “lincomycin” as an alternative agent Oral - Infection due to a susceptible Gram positive organism in a patient with major (type 1 or acute) allergy to beta-lactams - For use combined with rifampicin for oral treatment of MRSA - - Non-meningeal infections: Adult: 1 g IV 8-hrly Child: 25 mg/kg up to 1 g IV 8-hrly Norfloxacin (oral) Adult: 400 mg 12-hrly - Oseltamivir (oral) Adult: 75 mg twice per day for 5 days Child: Dose varies according to patient age and weight. Please refer to oseltamivir prescribing protocol on HNE Health intranet Piperacillin/Tazobactam (IV) Adult: 4/0.5 g IV 8-hrly Child: 100/12.5 mg/kg up to 4/0.5 g IV 8-hrly Higher doses may be required – please contact Infectious Diseases - - Version One Treatment of cytomegalovirus infection in an immunocompromised patient Prophylaxis for cytomegalovirus infection in a transplant recipient if oral therapy not suitable Infection due to a susceptible Gram positive organism in a patient with major (type 1 or acute) beta-lactam allergy Second line for severe sexually-acquired pelvic inflammatory disease in a patient with major (type 1 or acute) beta-lactam allergy (with gentamicin). Group B streptococcus prophylaxis in pregnant women with a penicillin allergy SWITCH TO ORAL CLINDAMYCIN AS SOON AS PRACTICABLE. Cystic fibrosis acute exacerbation Bronchiectasis where laboratory results demonstrate meropenem sensitivity All other uses must be first discussed with Infectious Diseases prior to prescription and/or registration. Directed treatment of multi-resistant Gram negative infection or empiric therapy in septic hospitalised patient who has known or suspected multiresistant bacterial colonisation. Directed treatment of urinary tract infection due to pseudomonas or other multi-resistant Gram negative susceptible to norfloxacin Prostatitis Second line for primary and secondary prophylaxis of spontaneous bacterial peritonitis in liver disease patients (400 mg daily). First line agent for this condition is oral sulfamethoxazole/trimethoprim 800/160 mg once daily. Proven, Influenza A (including H1N1 2009 and H3N2) and Influenza B on PCR requiring hospital admission where symptom onset < 48 hours Patients admitted to Intensive Care Unit with clinical evidence of ongoing/severe illness consistent with influenza where symptom onset < 48 hours. Influenza-like-illness requiring hospital admission who belong to a group vulnerable to severe outcomes of influenza where symptom onset < 48 hours Please refer to prescribing protocol in HNE intranet Cystic fibrosis acute exacerbation Suspected or proven pseudomonal infection (usually with an aminoglycoside once daily) Limb-threatening diabetic foot infection Limb threatening peripheral vascular disease in a non diabetic patient Uncontrolled intra-abdominal sepsis (used as a single agent) after 5 days of ampicillin, gentamicin and metronidazole Intra-abdominal sepsis where gentamicin contraindicated (allergy or preexisting hearing or vestibular problem) Hospital acquired pneumonia in HDU or ICU where patient admitted ≥5 days (6-hrly dosing frequency may be required) Aspiration pneumonia > 5 days after admission Systemic sepsis due to a suspected gastrointestinal/ biliary source Febrile neutropenia September 2010 Page 5 Restricted Antibiotic Rifabutin (oral) Adult: 300 mg daily Child: 5 mg/kg up to 300 mg daily Rifampicin (oral) (See TG: Antibiotic for dosing) Restricted Anti-infective Indications HNEH CG 10_06 Accepted Indications and Comments - Treatment of non-tuberculous Mycobacterium avium complex (MAC) infection - Ticarcillin/Clavulanate (IV) Vancomycin (IV) Note: Changes to dosing recommendations from August 2010: See TG: Antibiotic for dosing) Prophylaxis: See HNE Health Surgical Prophylaxis Clinical Practice Guideline) Vancomycin (oral) Adult: 125 mg 6-hrly Child: 3 mg/kg up to 125 mg 6-hrly Oral treatment for methicillin-resistant S. aureus with demonstrated rifampicin sensitivity (must be used in conjunction with oral fusidic acid 500 mg 12-hrly) Demonstrated mycobacterial infections Neisseria meningitides or Haemophilus influenzae type b (Hib) prophylaxis This drug is no longer stocked by John Hunter Hospital. Please see “piperacillin/tazobactam” as an alternative agent Treatment: - Empiric treatment of infections suspected to be caused by beta-lactam resistant Gram positive bacteria - Directed treatment of infections caused by beta-lactam resistant Gram positive bacteria - Directed treatment of infections caused by other Gram positive bacteria in patients with major beta-lactam allergy Surgical prophylaxis - Major surgical procedures in patients known to be colonised with MRSA. A single dose administered just prior to surgery is sufficient unless the procedure lasts more than 6 hours, in which case a second dose should be given - Second line endocarditis prophylaxis for genitourinary or gastrointestinal procedures in patients with major beta-lactam allergy (i.e. those who can not receive amoxycillin as first line agent) - Third line endocarditis prophylaxis for dental or upper respiratory tract interventions in patients unable to take the second line agent oral clindamycin (first line is amoxycillin) - Treatment of Clostridium difficile colitis that fails to respond to metronidazole - Severe and potentially life threatening C. difficile colitis (Consult Infectious Diseases). Usually given in combination with intravenous metronidazole. Note: Adult and paediatric CF patients who receive an aminoglycoside are dosed at 6am daily and require dose modification based on Area Under the Curve (AUC) pharmacokinetic evaluation. For patients being dose at JHH please contact the Immunology and Infectious Diseases Pharmacist (page: 5705) or consult Infectious Diseases or Respiratory Medicine. Version One September 2010 Page 6 Restricted Anti-infective Indications HNEH CG 10_06 IMPLEMENTATION PLAN Area Antimicrobial Working Party is responsible for overall implementation. This group has developed a strategic plan for 2010. Support for stewardship activities at remote sites is a key objective. At John Hunter Hospital, GUIDANCE Implementation Committee formed to oversee process of implementation of GUIDANCE-DS which is an essential element of restricted anti-infective management Intensive care antimicrobial liaison rounds (twice weekly at JHH, weekly at other sites) will continue across HNE Health at all intensive care units. Area Clinical Practice Guidelines and pathways for pneumonia, S. aureus bloodstream infection, aminoglycoside usage and surgical prophylaxis provide support for implementation. HAPS Microbiologists provide specific support for restricted anti-infective indications by selective (cascade) antimicrobial susceptibility reporting and direct clinician discussion over particular cases. Infectious Diseases consultants provide advice to clinicians consistent with these guidelines, supporting their use. Facility Managers and Pharmacists are to be provided with annotated quarterly facility antimicrobial usage reports that support targeted engagement of clinical staff. The Area Antibiotic Guideline lays down the expectations of clinicians to - follow Therapeutic Guidelines: Antibiotic and Area CPGs - follow criteria for early consultation with Infectious Diseases in specific cases Educational efforts to JMOs (Orientation sessions by Pharmacy and ID), Specialists, VMOs and GPs (Infection Matters Newsletter) will be completed. EVALUATION PLAN Antimicrobial usage monitoring via National Program occurs at all Acute Networks site. These data are subject to review by Pharmacy and the Area Antimicrobial Working Party. Drug Usage Evaluation surveys are done regularly at Acute Networks sites to identify opportunities for improvement and provide specific feedback to prescribers. GUIDANCE-DS at John Hunter (to be implemented on July 1st 2010) will provide for close analysis of restricted anti-infective prescription and use with timely feedback to prescribers. CONSULATION WITH KEY STAKEHOLDERS List of key stakeholder consulted including name and title • Infectious Diseases and Immunology • HAPS Microbiology • Area Quality Use of Medicines Committee • Anti-infective Working Group REFERENCES • Therapeutic Guidelines: Antibiotic, Edition 14 Version One September 2010 Page 7