Successful treatment of Pseudomonas aeruginosa infective endocarditis via haemodialysis outpatient parenteral antimicrobial therapy: case report

Sir, Pseudomonas aeruginosa infective endocarditis (IE) is rare and difficult to treat, often requiring long hospital admissions for intravenous antibiotics. Outpatient parenteral antimicrobial therapy (OPAT) is one option for the management of infection allowing for shorter inpatient stays. Certain antibiotics can be dosed for administration on haemodialysis, allowing for haemodialysis OPAT (HD-OPAT), but less is known about their pharmacokinetics and pharmacodynamics in this setting. Here we present a case of P. aeruginosa IE successfully treated with HD-OPAT using ceftazidime and oral ciprofloxacin. A woman in her late forties was admitted with fever and rigors during routine haemodialysis. She had a background of renal failure and had been stable on intermittent haemodialysis via a tunnelled line for 11 years. P. aeruginosa was isolated from three sets of blood cultures. Suspecting catheter-related infection, the line was removed and she was treated with intravenous ceftazidime 2 g once daily for 10 days followed by oral ciprofloxacin 500 mg twice daily for 2 days, with good clinical response. A transthoracic echocardiogram (TTE) showed no evidence of IE and a new line was inserted. The patient presented again 1 month later with similar symptoms, and P. aeruginosa was isolated from the line and peripheral blood cultures. A CT positron emission tomography (CT-PET) scan identified no source of recurrent bacteraemia. Owing to patient-related factors, the line was not removed and she received a 3 week course of intravenous gentamicin 100 mg post-dialysis and piperacillin/tazobactam 4.5 g twice daily plus 7 days of gentamicin plus heparin line locks. Within a week of completing treatment, she had recurrent positive blood cultures. A TTE was repeated, showing a tricuspid valve vegetation with moderate regurgitation. The haemodialysis catheter was removed and piperacillin/tazobactam and gentamicin were restarted for tricuspid valve P. aeruginosa IE. To facilitate outpatient management, options for ongoing delivery of antibacterials via haemodialysis were reviewed. Our patient weighed 95 kg and was 158 cm tall; she received high-flux haemodialysis three times weekly and was anuric. Ceftazidime exhibits time-dependent bactericidal activity against P. aeruginosa. It had been demonstrated that ceftazidime could be effectively dosed on haemodialysis, achieving adequate time above the MIC for susceptible organisms with intravenous post-dialysis ceftazidime doses of 1–2 g.1,2 Ceftazidime had an MIC of 2 mg/L for the P. aeruginosa isolate. It has previously been demonstrated that a target serum ceftazidime concentration of 4×MIC (i.e. 8 mg/L in this case) is required for optimal bactericidal activity.3,4 In view of the propensity for P. aeruginosa to become resistant to antimicrobials during therapy, we aimed to keep the ceftazidime levels well above the MIC throughout the treatment course.5 A dosing regimen of intravenous ceftazidime 2 g post-dialysis was chosen. Serum ceftazidime levels were monitored by LC6 during the longest interval between dialysis sessions (72 h). A peak serum concentration of 105 mg/L was achieved; this fell to 25 mg/L at 45 h and reached a pre-dialysis low (trough) of 7 mg/L 70 h post-dose. The dose was increased to 3 g post-dialysis, resulting in a trough level of 15 mg/L, thus achieving sufficient serum concentrations. See Figure 1. Serum ceftazidime concentrations following intravenous administration. Following this trial, a regimen consisting of intravenous ceftazidime 3 g prior to the 72 h dialysis interval and 2 g prior to the 48 h interval plus oral ciprofloxacin 500 mg twice daily was implemented (further aminoglycosides were avoided in view of the cumulative risk of toxicity). Treatment was continued for a total of 6 weeks for tricuspid valve IE with no adverse effects or clinical drug toxicity. After completion of therapy, the patient remained well, with no evidence of relapse at 3 months and negative surveillance blood cultures. P. aeruginosa is a rare cause of IE; in a prospective database of all IE cases managed at St Thomas’ Hospital (a tertiary referral centre for IE) from 1970 to 2016, we identified just 10 cases out of a total of 1562 (0.6%). Healthcare exposure is the second most commonly reported risk factor for this condition following intravenous drug use. Mortality for healthcare-associated P. aeruginosa IE was 40% in a recently published review.7 The BSAC recommends a combination of two active drugs, ideally to include a β-lactam and an aminoglycoside.8 However, evidence-based guidelines for antimicrobial choices are lacking, management is heterogeneous and relapse is common.7 OPAT has become the standard of care for many infections requiring prolonged intravenous antimicrobial treatment, and the European Society of Cardiology guidelines recommend its use for the management of IE where possible.9,10 Through therapeutic drug monitoring, we were able to demonstrate sustained therapeutic levels of ceftazidime dosed via intermittent haemodialysis. To our knowledge, this is the first report of a patient with P. aeruginosa endocarditis being managed successfully with ceftazidime administered via HD-OPAT. We therefore believe the described dosing regimen of ceftazidime administered via HD-OPAT is a viable option for the management of deep-seated infections caused by susceptible Gram-negative bacteria, potentially reducing the need for prolonged hospital admissions. This study was carried out as part of our routine work. None to declare.