Cephalosporins, Quinolones and Co-amoxiclav Prescribing Audit Executive Summary Background Antibiotic resistance poses a significant threat to public health, as antibiotics underpin routine medical practice. Broad-spectrum antibiotics (e.g. co-amoxiclav, quinolones and cephalosporins) should be avoided when narrowspectrum antibiotics remain effective because they increase the risk of Methicillin-Resistant Staphylococcus Aureus (MRSA), Clostridium difficile and resistant urinary tract infections. In the UK, 80% of antibiotic prescribing occurs in primary care, with over half for respiratory tract infections. The inappropriate use of antibiotics is related to bacterial resistance. The UK five-year antimicrobial resistance strategy aims to slow the development and spread of resistance. 1 Guidance by Public Health England (PHE) makes clear recommendations about when broad-spectrum antibiotics should be prescribed. By reviewing the use of these antibiotics in primary care retrospectively, clinicians can assess if this guidance is being followed and, where appropriate, make specific changes to clinical practice. 2 Key Findings 1. 71% of patients on prophylactic antibiotic therapy were on long-term treatment and of these 45% were highlighted for a review by practice pharmacists. Most patients were on long-term prophylactic treatment with cephalosporins for the prevention of UTIs. 2. 11% of patients who were treated with a cephalosporin for a UTI were also sensitive to either nitrofurantoin or trimethoprim, which should have been prescribed first line. In addition for 39% of patients, cephalexin was prescribed first line as empirical treatment over trimethoprim and nitrofurantoin. 3. Co-amoxiclav was only prescribed in line with PHE guidance in 28% of patients. In 43% of patients prescribed co-amoxiclav, this was not the appropriate choice in line with PHE guidance. In 20% of patients the choice and duration were not in line with PHE guidance, primarily where 7 days treatment was prescribed when a 5- day course was recommended. 4. 55% of prescribing of quinolones was in line with PHE guidance, however this apparent higher percentage of compliance compared with prescribing of co-amoxiclav and cephalosporins was due to 100% compliance of ofloxacin prescribing with PHE guidance. Quinolones were not the appropriate choice of antibiotic for 27% of patients. Recommendations Practice pharmacists to re-emphasise to GPs PHE guidance with respect to the choice of prescribing of first line ciprofloxacin, cephalosporins and co-amoxiclav and refer to further NICE CKS guidance for further detail on specific indications listed. Approximately half of patients on long term prophylactic antibiotic therapy, predominantly for UTIs and treated with cephalosporins, require a review of treatment with the outcome of the review documented. City and Hackney CCG to develop more focused audits for prescribing antibiotics as highlighted from this audit. Suggested areas are long term prescribing of antibiotics for prophylaxis and prescribing of antibiotics for UTIs. Clear communication is required from secondary care regarding the duration of prophylactic therapy for UTIs and patients should be reviewed every 6 months. Gain agreement locally between primary and secondary care for choice of antibiotic prescribing for common indications and appropriate doses, frequencies and durations of treatment in line with PHE guidance, as currently there is a wide variation. In addition discussion of referral or further treatment options when primary antibiotic courses are unsuccessful. 1
INTRODUCTION Antibiotic resistance poses a significant threat to public health, as antibiotics underpin routine medical practice. Broad-spectrum antibiotics (e.g. co-amoxiclav, quinolones and cephalosporins) should be avoided when narrowspectrum antibiotics remain effective because they increase the risk of Methicillin-Resistant Staphylococcus Aureus (MRSA), Clostridium difficile and resistant urinary tract infections. In the UK, 80% of antibiotic prescribing occurs in primary care, with over half for respiratory tract infections. The inappropriate use of antibiotics is related to bacterial resistance. The UK five-year antimicrobial resistance strategy aims to slow the development and spread of resistance. 1 Quinolones are recommended first line by Public Health England (PHE) only in limited situations such as in acute pyelonephritis, acute prostatitis or pelvic inflammatory disease. Resistance to quinolones is increasing at a considerable rate (for example, quinolone-resistant Neisseria gonorrhoeae), affecting all the quinolones. Guidance by PHE makes clear recommendations about when quinolones, co-amoxiclav, and cephalosporins should be prescribed. By reviewing the use of these antibiotics in primary care retrospectively, clinicians can assess if this guidance is being followed and, where appropriate, make specific changes to clinical practice. 2 Patients on long-term antibiotic therapy should also be included in this audit to review appropriateness of ongoing therapy and antibiotic choice. To review the prescribing of cephalosporins, quinolones and co-amoxiclav in line with PHE guidance. AIM METHOD To ensure that all strengths and brand names are included. The following were included: Quinolones Cephalosporins Co-Amoxiclav Ciprofloxacin (Ciproxin ) Levofloxacin (Tavanic ) Moxifloxacin (Avelox ) Nalidixic Acid Norfloxacin Ofloxacin (Tarivid ) Cefaclor (Distaclor, Distaclor MR ) Cefadroxil Cefalexin (Ceporex, Keflex ) Cefixime (Suprax ) Cefradine Cefuroxime (Zinnat ) Co-amoxiclav (Augmentin ) 1. Up to 30 patients who were prescribed a cephalosporin, a quinolone or co-amoxiclav from 1 st November to 31 st December 2016 were randomly selected for audit from each practice. 2. The electronic data collection form was completed for each patient, using the guidance from PHE as a reference point. 3. Prescribing for each practice was due to be re-evaluated in February to March 2017. epact data from 1 st February to 31 st March 2017 will be analysed to indicate any changes in prescribing patterns of cephalosporins, quinolones and co-amoxiclav since the baseline audit. 2
STANDARDS No. CRITERIA CCG TARGET Average 1 Co-amoxiclav is prescribed in line with PHE guidance.* 28% 100% 2 Cephalosporins are prescribed in line with PHE guidance.* 17% 100% 3 Quinolones are prescribed in line with PHE guidance.* 55% 100% 4 Patients prescribed a quinolone, co-amoxiclav or cephalosporin for long-term 70% 100% prophylaxis, have been reviewed for appropriateness of antibiotic choice since initiation of treatment. (Actual data based on whether patient has had a medication review in the last 12 months) *(If prescribing is outside of PHE recommendations, then it complies with recommendations from secondary care, microbiology or is in line with CKS guidance). RESULTS The broad-spectrum antibiotic prescribing audits were undertaken by PSPs and submitted for all 43 GP practices. One practice has a unique patient population and was therefore excluded. Data was collected for 807 patients. Table 1. Total Number of Broad Spectrum Antibiotics Prescribed Antibiotic prescribed Prescribed for Treatment Prescribed for Prophylaxis Total Co-amoxiclav 284 7 291 (41%) Quinolones 208 7 215 (25%) Cephalosporins 228 73 301 (34%) Total 720 (89%) 87 (11%) 807 Compliance with each of the 4 standards is outlined below. STANDARD 1 (TARGET = 100%) Yes No Unknown Co-Amoxiclav is prescribed in line with PHE guidance* *(If prescribing is outside of PHE recommendations, then it complies with recommendations from secondary care, microbiology or is in line with CKS guidance). 40 (28%) 104 (72%) Total number of patients prescribed co-amoxiclav Prescribed in line with PHE guidance PHE Indication 146 34 Non PHE Indication 138 NA Total 284 34 138 patients were prescribed co-amoxiclav for an indication outside of the PHE guidance and for 23 (17%) of these patients, treatment was recommended by secondary care. 2 3
Co-amoxiclav Co-amoxiclav Prescribed for Indications within PHE Guidance Total no. of Additional information patients Prescribed in line with PHE guidance 34 Prescribing complies with recommendations from secondary care/microbiology or is in line with CKS guidance 6 Choice of antibiotic is not in line with PHE guidance 63 Choice and duration of antibiotic are not in line with PHE 29 Choice of antibiotics appropriate, but dose/frequency/duration are not in line with PHE guidance 10 Prescribed multiple courses of the same antibiotic 2 Unknown if appropriate, lack of additional information 2 Total 146 STANDARD 2 (TARGET = 100%) Yes No Unknown Cephalosporins are prescribed in line with PHE guidance* *(If prescribing is outside of PHE recommendations, then it complies with Used first line for many patients 2 MSU samples not sent off 1 patient had 8 courses of co-amoxiclav 35 (17%) 174 (83%) 3 recommendations from secondary care, microbiology or is in line with CKS guidance). Prescribing for 9 (56%) out of 16 patients, prescribed a cephalosporin for an indication outside of the PHE guidance, complied with recommendations from secondary care, microbiology or was in line with CKS guidance. A follow-up letter from secondary care suggested stopping treatment for one patient, which was subsequently stopped by the GP on recommendation from the practice pharmacist undertaking the audit. Total number of patients prescribed a cephalosporin Prescribed in line with PHE guidance Urinary Tract Infection (UTI) Treatment 192 31 Other PHE Indication 20 1 Non PHE Indication 16 NA Total 228 32 Breakdown of Cephalosporin prescribing for the treatment of UTI Findings Total no. of patients Prescribed in line with PHE guidance 31 Prescribing complies with recommendations from secondary care/microbiology 3 Microbiology sensitivities to nitrofurantoin/trimethoprim 21 Nitrofurantoin/trimethoprim should have been used first/second line 75 Choice and duration of antibiotic treatment is not in line with PHE guidance 38 Choice of antibiotic okay, but dose, frequency or duration not in line with PHE guidance 21 Unknown if appropriate, lack of additional information 3 Total 192 Additional information 1 patient had 8 courses 4
STANDARD 3 (TARGET = 100%) Yes No Unknown Quinolones are prescribed in line with PHE guidance* *(If prescribing is outside of PHE recommendations, then it complies with recommendations from secondary care, microbiology or is in line with CKS guidance). Quinolones Total number of patients prescribed a quinolone Prescribed in line with PHE guidance PHE Indication 161 61 Non PHE Indication 47 NA Total 208 61 Prescribing for 13(28%) out of the 47 patients, prescribed a quinolone for an indication outside of the PHE guidance, complied with recommendations from secondary care, microbiology or was in line with CKS guidance. It was difficult to ascertain the severity of the condition for some patients and therefore to know if prescribing was appropriate due to a lack of information. Quinolones prescribed for an indication in PHE Guidance Quinolone Number patients In line with PHE Guidance Ciprofloxacin 141 43 Levofloxacin 2 0 Ofloxacin 18 18 Total 161 61 86 (55%) 69 (45%) 6 Ofloxacin was prescribed for Pelvic Inflammatory Disease and Epididymitis and 100% of prescribing was in line with PHE guidance. Treatment of UTIs and upper and lower respiratory tract infections accounted for 55% of ciprofloxacin prescribing. Quinolones Total number of patients Prescribing in line with PHE guidance 61 Prescribing complies with recommendations from secondary care/microbiology or is in line with CKS guidance. 25 Additional information 3 patients have had multiple Choice of antibiotic is not in line with PHE guidance courses of quinolones and 44 need referring Choice and duration of antibiotic are not in line with PHE guidance 6 Choice of antibiotic is appropriate, but the dose/frequency/duration is not in line with PHE guidance 16 2 MSUs not sent off Multiple courses of antibiotic have been prescribed for the same patient 3 Unknown if appropriate, lack of additional information 6 Total 161 2 patients were prescribed 3 courses in a short period of time 5
STANDARD 4 (TARGET = 100%) Yes No Patients prescribed a quinolone, co-amoxiclav or cephalosporin for long-term prophylaxis, have been reviewed for appropriateness of antibiotic choice since initiation of treatment. (Actual data based on whether patient has had a medication review in the last 12 months) 61 (70%) 26 (30%) Of the 87 patients on prophylactic broad-spectrum antibiotics, 61 (70%) had had a medication review in the last 12 months. 62 (71%) patients are on long-term treatment with broad-spectrum antibiotics, ranging from over 6 months to 13 years. Of concern may be that nearly a fifth of patients on prophylactic antibiotics have been taking them for 3 or more years with 11% having taken them for 6 or more years. Antibiotic UTI Prophylaxis Other Indication Total Cephalexin 67 3 70 Ciprofloxacin 3 4 7 Co-amoxiclav 3 4 7 Cefradine 2 0 2 Cefuroxime 1 0 1 Total 76 (87%) 11 (13%) 87 87 patients were on prophylactic antibiotic treatment with a quinolone, co-amoxiclav or a cephalosporin. 76 (87%) patients were on broad spectrum antibiotics for the prophylaxis of Urinary Tract Infection (UTI) and 67 (77%) patients were treated with cephalexin for UTI prophylaxis. PHE guidance was not applicable for 11 patients, as the indication documented as to why they were on prophylactic antibiotics was not listed in the PHE guidance. 6 (55%) of these patients were under specialist care. UTI Prophylaxis Prescribing of a broad spectrum antibiotic was recommended by secondary care for 37 (43%) of patients. Prescribing is not in line with PHE guidance for UTI prophylaxis for 19 (22%) patients. Duration of Treatment with Prophylactic Antimicrobials 0-3m 6m- 1yr 1-2 yrs 3-5yrs 6-10yrs 11-13yrs Long term Unknown Ciprofloxacin 0 1 1 1 0 0 2 2 Cephalosporins 16 2 2 5 9 1 34 1 Co-amoxiclav 0 1 1 0 0 0 2 3 Total 16 4 4 6 9 1 38 9 28 (45%) patients on long term treatment need a review as indicated by practice pharmacists in the additional notes section when completing the data collection form. Treatment may have been initiated by a specialist for many of these patients and the need for continued treatment may not have been considered to be reviewed. Practice pharmacists have raised with GPs where a review of treatment is required. 1 patient will be switched to nitrofurantoin and another has been recommended to stop prophylactic therapy, but is reluctant to do so. Discussion and Conclusion The broad spectrum antibiotic audit showed that co-amoxiclav was only prescribed in line with PHE guidance in 28% of patients. In 43% of patients prescribed co-amoxiclav, this was not the appropriate choice in line with PHE guidance. In 20% of patients the choice and duration was not in line with PHE guidance, primarily where 7 days treatment was prescribed when a 5 day course was recommended. Co-amoxiclav was commonly prescribed first line or second line for lower and upper respiratory tract infections, when first line treatment options do not appear to have been considered. 6
A limitation to auditing antibiotic prescribing in line with PHE guidance was when there was treatment failure and establishing why a certain treatment was not suitable for a patient and what the next step was as second line treatment options were not always recommended or included in the PHE guidance. The NICE Clinical Knowledge Summaries (CKS) are useful to refer to where appropriate and relevant, however without additional patient information, it was difficult to ascertain in some cases the exact rationale for treatment. Practice pharmacists did confirm that some GPs refer to local antibiotic guidelines from Homerton University Hospital. Co-amoxiclav was also prescribed for numerous indications outside of PHE guidance making it difficult to audit appropriateness of treatment and this was also outside the scope of this audit. 84% of cephalosporins prescribed for treatment of infections were to treat UTIs. If treatment of a UTI is indicated, then nitrofurantoin or trimethoprim are recommended as first line options. 11% of patients who were treated with a cephalosporin were also sensitive to either nitrofurantoin or trimethoprim, which should have been prescribed first line. In addition for 39% of patients, cephalexin was prescribed first line as empirical treatment over trimethoprim and nitrofurantoin. In 20% of patients the choice and duration of cephalosporin prescribed was not in line with PHE guidance. 55% of prescribing of quinolones was in line with PHE guidance, however this higher percentage of compliance compared with prescribing of co-amoxiclav and cephalosporins was due to 100% compliance of ofloxacin prescribing with PHE guidance. Quinolones were not the appropriate choice of antibiotic for 27% of patients and in 10% the quinolones were an appropriate choice, but the dose, frequency or duration of treatment was not in line with PHE guidance. 70% of patients prescribed a quinolone, co-amoxiclav or cephalosporin for long-term antibiotic prophylaxis had had a medication review in the past 12 months. However this does not necessarily mean than the appropriateness of antibiotic choice has been reviewed since initiation of treatment. 71% of patients on prophylactic antibiotic therapy were on long-term treatment, classified as on therapy for more than 6 months and of these 45% were highlighted for a review by practice pharmacists. Most patients were on long term prophylactic treatment for the prevention of UTIs. There is weak evidence from a Cochrane systematic review that continuous antibiotic use reduces the recurrence of urinary tract infections more than placebo but they are associated with more adverse effects There is insufficient direct evidence to prefer any particular antibiotic over another for prophylaxis of a UTI. Trimethoprim and nitrofurantoin are recommended options for prophylaxis of recurrent UTI because they are narrow spectrum antibiotics and are generally preferred over broad spectrum antibiotics due to concerns over increasing the risk of Clostridium difficile, MRSA, and resistant UTIs. Both trimethoprim and nitrofurantoin are licensed for the prophylaxis of recurrent UTI. Most patients on prophylactic UTI therapy with cephalexin in this audit were prescribed a dose of 250mg once daily. Cephalexin is not licensed for UTI prophylaxis, however we are aware that it is commonly prescribed for this indication. The British National Formulary recommends a dose of 125mg each night. 3 Recommendations Practice pharmacists to re-emphasise to GPs PHE guidance with respect to the choice of prescribing of first line ciprofloxacin, cephalosporins and co-amoxiclav and refer to further NICE CKS guidance for further detail on specific indications listed. Approximately half of patients on long term prophylactic antibiotic therapy, predominantly for UTIs and treated with cephalosporins, require a review of treatment with the outcome of the review documented. City and Hackney CCG to develop more focused audits for prescribing antibiotics as highlighted from this audit. Suggested areas are long term prescribing of antibiotics for prophylaxis and prescribing of antibiotics for UTIs. Clear communication is required from secondary care regarding the duration of prophylactic therapy for UTIs and patients should be reviewed every 6 months. 7
Gain agreement locally between primary and secondary care for choice of antibiotic prescribing for common indications and appropriate doses, frequencies and durations of treatment in line with PHE guidance, as currently there is a wide variation. In addition discussion of referral or further treatment options when primary antibiotic courses are unsuccessful. References 1. TARGET antibiotics toolkit; Royal College of General Practitioners 2. Management of infection guidance for primary care for consultation and local adaptation; Public Health England; July 2015 3. Clinical Knowledge Summaries; July 2015; https://cks.nice.org.uk/urinary-tract-infection-lower-women 8