Treatment of peritonitis in patients receiving peritoneal dialysis Antibiotic Guidelines. Contents

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Treatment of peritonitis in patients receiving Antibiotic Guidelines Classification: Clinical Guideline Lead Author: Jude Allen (Pharmacist) Additional author(s): Dr David Lewis, Dr Dimitrios

1 Treatment of peritonitis in patients receiving Antibiotic Guidelines Classification: Clinical Guideline Lead Author: Jude Allen (Pharmacist) Additional author(s): Dr David Lewis, Dr Dimitrios Poulikakos, Sister Joanne Martin Original document also written by Sister Helen Hannay, Lesley Lappin, Manager, renal clinical nurse specialists. Dr C Subudhi, Consultant Microbiologist Authors Division: DCSS & Tertiary Medicine Unique ID: 144TD(C)25(D3) Issue number: 4.1 Expiry Date: January 2019 Contents Section Page Intro Who should read this document 2 Key practice points 2 Background/ Scope/ Definitions 2 What is new in this version 3 Guideline Introduction 3 Definition of Peritonitis 3 Identification of Peritonitis 3 Administration of Antibiotic Therapy 3 Continuation of Antibiotic Therapy 5 Alternative Antibiotics 6 Duration of Therapy 6 Holiday Dialysis Prophylaxis 7 Contamination protocol 7 Fungal peritonitis 8 Follow up and audit 10 Standards of Care 10 References and Supporting Documents 10 Roles and Responsibilities 11 Appendix 11 Document control information (Published as separate document) 12 Document Control Policy Implementation Plan Monitoring and Review Endorsement Equality analysis Page 1 of 11

2 Who should read this document? This policy applies to all clinical staff involved the prescribing of antimicrobials. Key Practice Points This document refers to the treatment of adult patients (unless otherwise stated). This document provides treatment guidelines for the treatment of bacterial and fungal peritonitis and is based on the recommendations of the International Society for (ISPD) adapted for local resistance patterns and practice. Recommended doses take into consideration end stage renal function and need for renal replacement therapy. Adjustments may be needed for the treatment of some patients at extremes of weight. Background Antimicrobial agents are among the most commonly prescribed drugs and account for 20% of the hospital pharmacy budget. Unfortunately, the benefits of antibiotics to individual patients are compromised by the development of bacterial drug resistance. Resistance is a natural and inevitable result of exposing bacteria to antimicrobials. Good antimicrobial prescribing will help to reduce the rate at which antibiotic resistance emerges and spreads. It will also minimise the many side effects associated with antibiotic prescribing, such as Clostridium difficile infection. It should be borne in mind that antibiotics are not needed for simple coughs and colds. In some clinical situations, where infection is one of several possibilities and the patient is not showing signs of systemic sepsis, a wait and see approach to antibiotic prescribing is often justified while relevant cultures are performed. This document provides treatment guidelines for the appropriate use of antibiotics. The recommendations that follow are for empirical therapy and do not cover all clinical circumstances. Alternative antimicrobial therapy may be needed in up to 20% of cases. Alternative recommendations will be made by the microbiologist in consultation with the clinical team. This document refers to the treatment of adult patients (unless otherwise stated). What is new in this version? Increased frequency of dosing for vancomycin. Duration of treatment for different organisms. Change in gentamicin dosing. Clarification about when fungal prophylaxis may be required. Addition of a contamination protocol. Clarification around vancomycin for holiday dialysis prophylaxis. Fungal peritonitis guidelines. Page 2 of 11

3 Guidelines Introduction Peritoneal dialysis is used for renal replacement therapy in end stage renal disease. Both continuous ambulatory (CAPD) and automated peritoneal dialysis (APD) are used at Salford Royal NHS Foundation Trust. Definition of peritonitis: Peritonitis in patients undergoing denotes inflammation of the peritoneum. This results in an increase in the number of white blood cells, leading to cloudiness of the fluid when drained out of the peritoneum. The cloudiness is almost invariably present and should be seen as the earliest detector of infection. The majority of patients will also complain of abdominal pain and/or tenderness. Identification of peritonitis International Society of Peritoneal Dialysis (ISPD) recommendations (2016) state that all patients presenting with cloudy effluent (dialysis bags) should be presumed to have peritonitis. This is confirmed by laboratory analysis of a dialysis effluent sample showing white cell count >100. The sample should be taken after at least a 2 hour dwell. A yellow topped sterile sample pot should be filled with 50ml of PD effluent and sent urgently to microbiology and the laboratory contacted. White cell count, culture, antibiotic sensitivities and gram stain should be requested. All patients with suspected or confirmed bacterial peritonitis should be notified to the renal community team. Administration of Antibiotic therapy. Where there is suspicion of peritonitis, samples must be taken for white cell count, culture and sensitivity. Immediately following the taking of samples, empirical antibiotic therapy should be given that provides both gram positive and gram negative cover. The BNF and SPC should be consulted to check for cautions/ contraindications/ and adverse effects in addition to potential drug interactions for an individual patient. Do not wait for confirmation of results or WCC before administering the first doses of antibiotic therapy. The patient s history of infection and any available sensitivity results must be considered when selecting initial therapy. Intraperitoneal administration of antibiotics for treating peritonitis is superior to intravenous administration and intermittent dosing is equally efficacious as continuous administration. Dwell time for the exchange containing antibiotics must be a minimum of 6 hours. Patients who usually undertake automated PD should perform a manual exchange to facilitate administration of antibiotics by this route. Page 3 of 11

4 Note vancomycin and gentamicin may be given in the same PD bag, providing different syringes are used to make the addition. Vancomycin and gentamicin are both compatible with standard dialysis fluid and icodextran products eg extraneal. Initial therapy: Initial therapy should provide adequate cover for the usual pathogens and consists of both vancomycin and gentamicin. Vancomycin 1000mg vial of vancomycin should be reconstituted with water for injection and drawn up into a 20ml syringe using ANTT. The vancomycin should be added to the PD fluid through the additive port on the PD bag. Patient weight Less than 70kg 70kg to 90kg Greater than 90kg Dose of vancomycin 1500mg 2000mg 2500mg Patients with allergies to vancomycin Discuss with renal pharmacist or duty microbiologist. Gentamicin Gentamicin injection is added directly to fluid. The 20mg/2ml, paediatric gentamicin amps should be used to ensure an accurate dose is measured. The dose should be calculated according to the patient s weight Patient weight Dose of Gentamicin mls of 20mg/2ml amps Less than 50Kg 30 mgs 3mls 50 to 80Kg 40 mgs 4mls Greater than 80Kg 50mgs 5mls Page 4 of 11

5 Continuation of antibiotic therapy. Until culture and sensitivity results are known, bacterial peritonitis should be treated with both vancomycin and gentamicin as below. Gram positive infections Where patients have received an initial dose of vancomycin, further doses will be required: CAPD: 5-7 days APD 3-5 days Where patients are responding to therapy, with reduced effluent white cell count, vancomycin levels do not need to be checked routinely during the treatment course. Where patients may not appear to be responding to treatment, consideration may be given to checking a vancomycin level to ensure systemic therapeutic levels are obtained and re-dosing should occur when levels fall below 15mg/L. This should be decided on an individual patient basis as systemic levels will be expected to be lower than levels at the site of infection if given directly into the peritoneal cavity. Enterococcal infections should preferentially be treated with a broad spectrum penicillin eg amoxicillin. Individual cases should be discussed with a microbiologist. Vancomycin allergic patients Discuss with renal pharmacist or duty microbiologist Gram negative infections Gentamicin therapy is the antibiotic of choice for gram negative infections. Alternative agent after discussion Ciprofloxacin 500mg twice daily Extended or repeated courses may increase adverse effects on the vestibular system and ototoxicity is a potential risk and repeated exposure should be avoided. Gentamicin intraperitoneal administration requires once daily dosing, in a dwell lasting at least 6 hours. For practical reasons this is usually the last peritoneal exchange bag of the day. The dose should be calculated according to the patients weight Page 5 of 11

6 Patient weight Dose of Gentamicin mls of 20mg/2ml amps Less than 50Kg 30 mgs 3mls 50 to 80Kg 40 mgs 4mls Greater than 80Kg 50mgs 5mls Alternative antibiotics Following culture and sensitivity reports alternative antibiotics may be indicated. Please contact microbiology and pharmacy for advice on compatibility and doses. Note the current BNF and SpC should be consulted for a full list of potential and actual drug interactions and a full drug history checked prior to prescribing. Taken from ISPD guidelines 2016 Antibiotic Aminoglycosides Gentamicin CAPD per exchange once daily Continuous mg/l all exchanges 8mg/l first dose then 4mg/l As above Amikacin 2mg/kg 25mg/l first dose then 12mg/l Penicillins Amoxicillin No data 150mg/l Quinolones Ciprofloxacin Oral ciprofloxacin No data mg twice daily by mouth 50mg/l Others Aztreonam 2g od 1000mg/l first dose then 250mg/l Daptomycin No data 100mg/l first dose then 20mg/l Teicoplanin 15mg/kg every 5 days 400mg/l first dose then 20mg/l Vancomycin As above Duration of Therapy Following the initial dose, antibiotic therapy will be required for a minimum of 14 days and should be guided by culture and sensitivities. If no growth is detected repeat PD fluid white cell count after 3 days. If infection resolving stop gentamicin, continue vancomycin for 14 days 3 doses If peritonitis does not respond within 7 days further discussion is warranted by the renal and microbiology team. Where necessary, tube replacement may be planned for recurrent or non-resolving bacterial peritonitis. Page 6 of 11

7 Coagulase negative staphylococcal infections: Staphylococcus aureus infections: Enterococci infections: discuss therapy with microbiology Other streptococcal infections: 14 days 3 doses 21 days 4 doses 21 days 4 doses 14 days 3 doses Culture negative peritonitis: repeat PD fluid white cell count after 3 days. If infection resolving stop gentamicin, continue vancomycin for 14 days 3 doses For most Gram negative infections the duration of therapy will be 21 days For pseudomonas or stenotrophomonas infections 2 antibiotics will probably be required for at least 21 days please discuss with microbiology For mixed Gram positive & Gram negative infections consider adding metronidazole and treating for 21 days. Antifungal prophylaxis This is not used routinely but should be considered on a case by case basis, particularly patients requiring repeated courses of antibiotics for recurrent or relapsing peritonitis or long courses of antibiotics for slowly resolving infection. Additional antibiotic This is not used routinely but may be considered after discussion for slowly resolving infection or specific antibiotic sensitivities. Recurrent and relapsing infections These patients may have already received courses of antibiotics without full clearance of infection and are at risk of non-resolving infection and long exposure to antibiotics. They should have vancomycin and/or gentamicin levels taken after 3-5 days and dosage schedule reviewed. Holiday dialysis treatment of peritonitis Antibiotics should be provided to patients who are travelling on holiday where appropriate on an individual case basis. Consideration should be given to the patients history of peritonitis when choosing appropriate antibiotics and a discussion with microbiology and the community dialysis team. Where indicated, Patients should be given at least 3 doses of vancomycin for empirical therapy and advised to take this to their local renal centre for administration. Gram negative cover may be given either in the form of gentamicin injections as described above or oral ciprofloxacin tablets 500mg bd for 21 days. Page 7 of 11

8 Contamination Guidelines Line Contamination would be classed as :- - The exposed end of the catheter coming into contact with any non-sterile object - Disconnection of the extension line from the titanium / plastic adaptor Treatment Intraperitoneal Vancomycin A new extension line should be connected aseptically initially Patient weight Less than 70kg 70kg to 90kg Greater than 90kg Dose of vancomycin 1500mg 2000mg 2500mg The vancomycin should be reconstituted with water for injection and drawn up into a 20ml syringe using ANTT. The vancomycin should be added to the PD fluid through the additive port on the PD bag. The patient should be advised to allow at least a 6 hour dwell Fungal Peritonitis Guidelines Introduction Fungal peritonitis is an emergency and requires urgent action. In the majority of cases (PD) catheter removal is the only effective management of fungal peritonitis. Catheter removal should be arranged as soon as possible following detection of yeast or fungi in cultured fluid samples. The community dialysis team must be informed immediately when yeast is obtained in a sample. Renal patients with a catheter who present with suspected peritoneal infections will have a sample sent for culture and sensitivity testing routinely. If yeast or fungi is identified during the laboratory testing, this will be flagged as an emergency by the duty microbiologist. The result will be communicated as follows: Page 8 of 11

9 Monday to Friday 9am 5pm All other times Renal Baton Bleep Holder Pager number Or Community Dialysis Renal On-call SpR Contact through switchboard The responsible SpR must arrange urgent admission to a renal ward if the patient is at home. Catheter Removal Arrangements should be made to remove the PD catheter as soon as practicable (aim to remove within 24 hours). This will require liaison with the on-call surgeons and may necessitate adding to the emergency theatre list. Medically inserted catheters may be removed under local anaesthetic by trained operators, if other intra-abdominal pathology is not suspected (e.g. bowel perforation). Drug therapy Anti-fungal therapy must be prescribed and given immediately on detection of yeast in fluid samples. Initial empirical therapy: IV voriconazole (see appendix for further information on voriconazole) 6mg/kg every 12 hours for 24 hours Followed by 3-4mg/kg every 12 hours Weight (Kg) IV Initial Dose and 12 hours later (2 doses only) IV or ORAL Maintenance dose after 24 hours Given every 12 hours Less than 55Kg 300mg 200mg 56 to 75kg 400mg mg Greater than75kg 500mg 300mg Therapy may be switched to oral therapy after 24 hours providing the PD catheter has been removed and the patient is not clinically compromised as assessed by a senior doctor. IV therapy may be continued if necessary however, a switch to oral should be made as soon as possible and must be reviewed daily. Patients requiring more than 7 days therapy may require therapeutic drug monitoring. This should be discussed with the duty microbiologist and Renal Pharmacist as required. Page 9 of 11

10 Modification of therapy Therapy should be modified in response to sensitivity results from the laboratory. Note, due to the slow nature of fungal/ yeast growth, identification and antifungal sensitivity results may take 5-7 days. Patient review after 72 hours If patients are improving clinically continue to monitor and adjust therapy according to sensitivity reports. Patients who are not responding to therapy after 72 Hours If patients are further deteriorating clinically increasing white cell count raised temperatures increasing CRP Early warning score >3 Current therapy should be checked against known sensitivity results. If no sensitivity results are known, after 72 hours, discuss with microbiology. Duration of therapy All patients will require three weeks of antifungal therapy with a minimum of 14 days post removal of catheter. Follow up and audit Details for all renal patients with peritonitis are recorded and audited by the community dialysis team for internal audit and submitted for North West Regional Renal Audit. When available, information will also be submitted to the Renal Association Renal Registry for national audit. Standards Document the Indication/rationale for antimicrobial therapy, including clinical criteria relevant to this. Review and document the patient s allergy status Ensure the choice of antibiotic complies with the antibiotic guidelines and you have documented any clinical criteria relevant to the choice of agent. Document a management plan including a stop or review date. Where relevant, consider drainage of pus or surgical debridement/removal of foreign material. Page 10 of 11

11 References and Supporting Documents 1. ISPD Guidelines/ recommendations related infections recommendations:2016 update 2. Peritoneal Dialysis International, Vol. 30, pp Roles and responsibilities All clinical staff involved in the prescribing of antimicrobials to adhere to this policy including full documentation on EPMAR as detailed. Appendices None Page 11 of 11

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