Clinical Effectiveness of Continuous Infusion Flucloxacillin in the Outpatient Parenteral Antimicrobial Therapy (OPAT) Setting in a UK Hospital: A Service Evaluation
Abstract
:1. Introduction
2. Materials and Methods
3. Results
3.1. Intravenous Access and Method of Administration
3.2. Microbiology
3.3. Flucloxacillin Dosing and Adjunctive Oral Therapy
3.4. Diagnoses and Treatment Outcomes
3.5. Adverse Effects and Complications
4. Discussion
- The use of continuous infusion elastomeric devices in the OPAT setting has expanded in recent years due to the increasing availability of stability data [11]. Stability data for flucloxacillin in particular [5] enables patients to receive a narrow-spectrum first-line treatment option for serious MSSA infection, which complements the antimicrobial stewardship agenda [12]. Previous studies reviewing the use of continuous infusion flucloxacillin for complex MSSA infection in the OPAT setting have shown that sufficient flucloxacillin concentrations are achieved and have shown it to be well tolerated with high cure rates [6,7,8]. Favourable outcomes have also been shown by other OPAT centres in the UK, using alternative outcome measures [9];
- Overall, 95% (n = 37) of patients reviewed had an OPAT outcome of ‘treatment aim attained’, though this was complicated in 8 patients. A successful outcome of ‘Treatment aim attained uncomplicated’ was observed in 29/39 (74%) patients. Thirty patients (77%) had an MSSA bacteraemia and there were a significant number of particularly difficult-to-treat infections with discitis (alone or in conjunction with infection at other sites) and endocarditis being the predominant diagnoses (44%, 17 patients). A systematic review [13] showed an overall mortality rate at 3 months of 27% and 30% at 1 year for S. aureus bacteraemia, with a higher mortality rate amongst those with underlying co-morbidities. In our cohort, there were no deaths within the 1-year follow-up period secondary to recurrence of MSSA infection. Further to the supportive data explained above, a low relapse rate of 5% (n = 2) within 1 year after treatment completion, in a cohort where 41% of patients had three or more underlying co-morbidities, provides further supportive evidence that the use of CIV flucloxacillin seems to be an effective treatment option for complicated MSSA infection in the OPAT setting. It is recognised that all patients in this cohort received a minimum of 2 weeks IV flucloxacillin therapy and were clinically stable prior to discharge on OPAT, and so this may be reflective of the satisfactory clinical outcomes attained. Direct comparison with other studies showing CIV flucloxacillin to be effective [6,7,8] is complex due to the differing number of diagnoses and differences in co-morbidities exhibited by the patient population;
- There were only two patients (5%) with an OPAT outcome of ‘treatment aim not attained’, in both cases, the patients were being treated for ‘discitis plus other sites’. One patient had disseminated MSSA bacteraemia, with a left shoulder septic arthritis, multi-level discitis, posterior epidural abscess, and a right, upper lobe cavitating pneumonia. The patient was re-admitted 22 days prior to the end of his planned 6 weeks total treatment due to increasing back pain. Repeat blood cultures were negative, and MRI showed no change to epidural abscess, but some new oedema at T5. The patient completed a total of 8 weeks IV flucloxacillin and was discharged with a further 4 weeks oral treatment with doxycycline and rifampicin, completing 12 weeks treatment in total. A 12-week treatment duration is not out of keeping with recommended treatment durations required to manage discitis, given difficulties with antibiotic penetration into discs. Whilst a randomised controlled trial showed non-inferiority for a treatment duration of 6 versus 12 weeks in the treatment of vertebral osteomyelitis, non-inferiority was not shown in all subgroups and the presence of S. aureus infection showed reduced chances of treatment success [14]. The second patient, treated for discitis, epidural abscess, and a right psoas collection, was re-admitted 3 weeks following the completion 6 weeks IV flucloxacillin (8 g) plus oral clindamycin. Repeat imaging showed disease progression requiring source control. The patient subsequently received a further 12 weeks of IV flucloxacillin (12 g/24 h) plus oral fusidic acid, with no evidence of relapse at 12 months. Treatment failure was considered secondary to inadequate source control rather than a failure of flucloxacillin. Interestingly, this patient was bacteraemic with the same organism (MSSA) 8 weeks prior to the initial episode described above and received treatment for endocarditis (2 weeks IV flucloxacillin followed by 4 weeks IV ceftriaxone on OPAT). The choice of ceftriaxone for the initial MSSA bacteraemia may be challenged by some given the concerns about the higher risk of treatment failure compared to anti-staphylococcal penicillins [2,3];
- In our patient cohort, one patient received a prolonged course of IV antibiotics for 6 weeks out of a total 12-week duration for prosthetic joint infection (debridement, antibiotics and implant retention (DAIR)). Whilst the prolonged intravenous duration may be seen as a treatment failure, given the outcomes published in the oral versus intravenous antibiotics for bone and joint infection (OVIVA) study [15]; the use of high-dose intravenous therapy aimed to provide the patient with the best chance of treatment success, given the multiple prior joint revisions on a background of immunosuppression;
- The low relapse rate of 5% (n = 2) within a significant follow-up period of 12 months is encouraging. Furthermore, relapse in both cases was not deemed due to a failure of flucloxacillin treatment. One relapse was on a background of multiple joint revisions and the re-introduction of immunosuppressant therapy and the other due to a new PICC line. Two patients required surgery within the 12-month follow-up period, which were not deemed a relapse, as surgery was an expected outcome prior to commencement of antibiotic therapy in both cases;
- Excluding the line related complications observed in two (5%) patients (axillary vein thrombosis and line related phlebitis), flucloxacillin was well tolerated by the majority of patients (87%, n = 34). Within our patient cohort, two required cessation of flucloxacillin due to suspected induced nephrotoxicity (normalisation of renal function was achieved upon cessation of therapy). This is a higher rate than that observed in other studies [6,7,8] where this adverse event was not observed. The incidence of nephrotoxicity is reported as very rare in accordance with the manufacturer’s product information [16]. It is, however, not an unexpected adverse effect [17,18] and reflects the importance of frequent monitoring of renal function in patients on prolonged treatment courses. Use of prolonged beta lactam infusions in an observational study did not show any significant increased risk of AKI versus intermittent dosing, though it is noted that this study did not include flucloxacillin [19];
- There are some disadvantages to the use of continuous infusion elastomeric devices including leakage and residual volumes, resulting in patients failing to receive the full prescribed dose. Residual volumes have been anecdotally reported by numerous OPAT centres, with piperacillin tazobactam often being more problematic compared to flucloxacillin [20,21]. In this patient cohort, there were no reports of leakage or incomplete infusion with any of the elastomeric flucloxacillin infusions. Whilst a retrospective review of nursing documentation was not undertaken as part of this evaluation, it is standard practice for the OPAT nurses to record the time and date the infusion was connected and the time and date of disconnection. Furthermore, the infusion volume remaining is documented, and it is standard practice for the OPAT nurse to report any issues around leakage or residual volumes to the OPAT pharmacist and to document on the OPAT PMS. The OPAT PMS was reviewed as part of this evaluation, and no documentation of incomplete infusion was recorded for any of the patients receiving continuous infusion flucloxacillin in this cohort. At our OPAT centre, our experience is that residual volumes are more problematic with piperacillin tazobactam. Due to the increasing frequency of residual volumes, particularly with 18g piperacillin tazobactam 24 hour infusions, our OPAT centre introduced the administration of extra bolus doses should there be greater than a 60 mL remaining infusion volume in May 2022. In all cases reasons for incomplete infusion are investigated. For example, line obstruction, inappropriate positioning, or storage of the device, and if remaining volumes continue to be problematic, alternative antibiotic therapy is sought.
5. Limitations
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Appendix A
Inclusion Criteria |
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Exclusion Criteria |
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Appendix B
Treatment Aim/Outcome | Description |
---|---|
Cure | To complete an agreed OPAT duration of therapy on either intravenous and/or complicated oral antimicrobials with no requirement for long-term antimicrobial therapy |
Improvement | To complete an agreed OPAT duration of therapy on either intravenous and/or complicated oral antimicrobials (a) as part of an agreed surgical infection management plan with further surgery planned or (b) where there is a requirement for subsequent long-term or an extended course of oral suppressive antimicrobial therapy, or (c) where potentially infective prosthetic material is still in situ. |
Palliation | To undertake a course of OPAT on either intravenous and/or complicated oral antimicrobials where there are agreed ceilings of care due to co-morbidities, with death being the likely outcome |
OPAT outcome | |
Treatment aim attained uncomplicated | Completed OPAT therapy as per treatment aim with no unplanned changes in antimicrobial agent, no adverse events, no planned or unplanned readmission related to the current OPAT episode, no readmission of ≥24 h for unrelated event |
Treatment aim attained-complicated | Completed OPAT therapy as per treatment aim but with one or more of the following: unplanned changes in antimicrobial agent, any adverse event including readmission for <24 h related to the current OPAT episode |
Treatment aim not attained | Failure to complete planned OPAT therapy for any reason other than readmission due to unrelated event, worsening of infection requiring re-admission or readmission for ≥24 h for any cause related to OPAT, including adverse events |
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Investigation/Follow Up | Frequency | Description/Further Information |
---|---|---|
Blood tests | Baseline prior to discharge on OPAT, then weekly till stop date | Baseline U&Es, FBC, LFTs, CRP, calcium, INR, and vitamin D. Weekly: U&Es, FBC, LFTs, CRP |
Multi-disciplinary ward round | Weekly until stop date | Ward round attended by OPAT consultant, OPAT registrar, specialist pharmacist and OPAT nurse |
Face to face clinic review | Week 1 on OPAT and at end of treatment | Face to face visits if required if problem identified |
Telephone consultation | If any complications | May do telephone consultation at end of treatment, if face to face not required |
OPAT nurse review | Daily/weekly | Daily if attending IVIC or OPAT nurse connecting the device. Weekly if self-administering |
Line care (clean site and dressing change) | Weekly | Line removed at end of treatment |
Review by referring specialty consultant | End of treatment or sooner if complications arise | If complication e.g., drainage/surgical intervention required |
Number of Co-Morbidities | No. of Patients |
---|---|
None | 4 |
One | 8 |
Two | 11 |
Three or more | 16 |
Co-Morbidity | No. of Patients |
---|---|
Hypertension | 12 |
Diabetes (type 1 and 2) | 11 |
Cardiac disease | 8 |
Osteoarthritis/Rheumatoid arthritis | 7 |
COPD #/Asthma | 7 |
Obesity (over 100 kg) | 7 |
Atrial fibrillation | 6 |
Mental health disorder | 5 |
Cancer | 5 |
Liver disease | 4 |
Obstructive sleep apnoea | 2 |
Aneurysm | 2 |
Miscellaneous * | 1 * |
Infective Indication | No. of Patients | No. of Patients with a Bacteraemia | Daily Dose (g) | Duration on OPAT (Days) | Intended Total Duration (Weeks) | No. of Patients on Concurrent oral Therapy | Adverse Effects/Complications | OPAT Outcome | Follow-Up (Minimum 12 Months) |
---|---|---|---|---|---|---|---|---|---|
Discitis plus other sites * | 6 | 6 | 8–12 | 4–31 | 6 | 4 Rifampicin 1 Clindamycin | 1 AKI (stage1) 1 Rash | Treatment aim attained—uncomplicated: 2 Treatment aim attained—complicated: 2 Treatment aim not attained: 2 | 4 No relapse 2 required readmission $ |
Endocarditis | 7 | 7 | 8–12 | 6–25 | 4–6 | 3 Rifampicin | 1 AKI (stage1) | Treatment aim attained uncomplicated: 6 Treatment aim attained complicated: 1 | No relapse |
Parotitis | 1 | 1 | 8 | 9 | 2 | 1 Metronidazole | 0 | Treatment aim attained uncomplicated | No relapse |
Vascular graft infection | 2 | 2 | 12 | 24–43 | 6 | 1 Rifampicin | 0 | Treatment aim attained uncomplicated: 2 | No relapse |
Central line related | 1 | 1 | 8 | 10 | 4 | None | 0 | Treatment aim attained uncomplicated | Repeat MSSA bacteraemia and septic arthritis 6 months later. |
Multi focal septic arthritis | 1 | 0 | 12 | 14 | 6 | 1 Rifampicin | 0 | Treatment aim attained uncomplicated | No relapse |
Necrotising otitis externa | 1 | 0 | 8 | 21 | 6 | None | Positive ear swab for Pseudomonas changed to Piperacillin/ tazobactam | Treatment aim attained complicated | No relapse |
Septic arthritis | 2 | 1 | 12 | 5–29 | 2–6 ** | None | 0 | Treatment aim attained uncomplicated 2 | No relapse |
Discitis | 4 | 4 | 8–12 | 13–71 | 6–12 | 1 Clindamycin 1 Rifampicin | 1 AKI (stage 1) 1 Cellulitis (line site) | Treatment aim attained uncomplicated:2 Treatment aim attained complicated 2 | No relapse |
Surgical-related deep wound infection | 1 | 0 | 12 | 9 | 2 | None | Vaginal thrush Axillary vein thrombosis | Treatment aim attained complicated | No relapse |
Septic arthritis and epidural abscess | 2 | 2 | 8 | 18–22 | 4–6 | 2 Rifampicin | 0 | Treatment aim attained uncomplicated: 2 | No relapse |
Prosthetic joint infection (DAIR) | 1 | 0 | 8 | 34 | 12 (6 IV + 6 oral) | 1 Rifampicin | 0 | Treatment aim attained complicated | Relapse |
Peripheral line related | 1 | 1 | 8 | 7 | 2 | None | 0 | Treatment attained uncomplicated | Died 4 months after completion unrelated |
Epidural abscess | 1 | 1 | 12 | 9 | 2 (IV) + 4 oral | 1 Rifampicin | 0 | Cured Treatment attained uncomplicated | No relapse |
Empyema | 1 | 1 | 12 | 15 | 4 | None | 0 | Treatment attained uncomplicated | No relapse |
Osteomyelitis (surgical related) | 4 | 0 | 8 | 2–33 | 6–12 # | 3 Rifampicin | 1 nausea | Treatment attained uncomplicated: 4 | 2 no relapse 1 elective below knee amputation 1 elective 2 stage revision |
Osteomyelitis (non-surgical related) | 3 | 3 | 8–12 | 10–37 | 6 | 1 Metronidazole | 0 | Treatment aim attained uncomplicated 3 | No relapse |
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Clarkson, A.M.; Snape, S. Clinical Effectiveness of Continuous Infusion Flucloxacillin in the Outpatient Parenteral Antimicrobial Therapy (OPAT) Setting in a UK Hospital: A Service Evaluation. Antibiotics 2024, 13, 153. https://doi.org/10.3390/antibiotics13020153
Clarkson AM, Snape S. Clinical Effectiveness of Continuous Infusion Flucloxacillin in the Outpatient Parenteral Antimicrobial Therapy (OPAT) Setting in a UK Hospital: A Service Evaluation. Antibiotics. 2024; 13(2):153. https://doi.org/10.3390/antibiotics13020153
Chicago/Turabian StyleClarkson, Annette Margaret, and Susan Snape. 2024. "Clinical Effectiveness of Continuous Infusion Flucloxacillin in the Outpatient Parenteral Antimicrobial Therapy (OPAT) Setting in a UK Hospital: A Service Evaluation" Antibiotics 13, no. 2: 153. https://doi.org/10.3390/antibiotics13020153
APA StyleClarkson, A. M., & Snape, S. (2024). Clinical Effectiveness of Continuous Infusion Flucloxacillin in the Outpatient Parenteral Antimicrobial Therapy (OPAT) Setting in a UK Hospital: A Service Evaluation. Antibiotics, 13(2), 153. https://doi.org/10.3390/antibiotics13020153