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The Role of Continuous Meropenem Administered via Elastomeric Infusers as Outpatient Parenteral Antimicrobial Therapy for the Treatment of Melioidosis in Tropical Australiaa

Submitted:

10 September 2026

Posted:

11 September 2026

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Abstract
Background: Intravenous meropenem and ceftazidime are the preferred antibiotics for the intensive phase treatment of melioidosis. Most patients receive intravenous ceftazidime via elastomeric infusers to complete treatment as outpatient parenteral antimicrobial therapy (OPAT). Concerns regarding meropenem’s stability in continuous infusion limit options when ceftazidime cannot be used. Methods: We reviewed all cases of melioidosis managed at Cairns Hospital from 2016 to 2026 and documented the rationale for patients receiving intravenous meropenem as a continuous infusion as OPAT. We recorded each Burkholderia pseudomallei isolate’s MIC for meropenem and the patients’ creatinine clearance, continuous infusion dose, serum meropenem concentrations, treatment duration and clinical course. Results: In 560 cases of melioidosis, 9 (2%) received meropenem as a continuous infusion as OPAT. This was due to an adverse drug reaction (ADR) to ceftazidime in 6/9 patients. The isolates’ median (range) MIC for meropenem was 1 (0.5-1) mg/L. All patients received twice daily elastomeric infusers; initial dosing was 1.5g 12-hourly in 5 patients and 3g 12-hourly in 4 patients. The initial median (range) meropenem random concentration was 6.5 (2.3-18.1) mg/L. The meropenem dose was increased in 2 patients following therapeutic drug monitoring (TDM). One patient was changed from meropenem to ceftazidime due to eosinophilia without end-organ sequelae; there were no other ADRs. All patients achieved clinical cure. Conclusion: Twice daily continuous meropenem infusions administered as OPAT are an alternative treatment option for select patients with melioidosis where ceftazidime cannot be used. The use of TDM can overcome concerns regarding stability and degradation in extended infusions.
Keywords: 
OPAT
;  
melioidosis
;  
tropical infections
;  
antibiotic therapy
;  
therapeutic drug monitoring
Subject: 
Medicine and Pharmacology  -   Tropical Medicine

Introduction

Melioidosis is an opportunistic, tropical infectious disease caused by the environmental bacterium Burkholderia pseudomallei. Most patients with melioidosis are bacteraemic, and a quarter present in septic shock; even in well-resourced health settings, the case-fatality rate of melioidosis is approximately 10%.1 Meropenem and ceftazidime are the antibiotics of choice for the initial intensive intravenous phase of treatment with Australian guidelines recommending meropenem for patients admitted to the intensive care unit and for those with neuromelioidosis.[1,2] Ceftazidime is used in patients without these features and, due its stability in elastomeric infusers, it is the preferred agent once patients improve and transition to outpatient parenteral antimicrobial therapy (OPAT).[3] This strategy, which involves administering ceftazidime to complete 2 to 8 weeks of intravenous treatment, depending on the manifestations and severity of the disease, has resulted in excellent outcomes in large prospective studies.[4]
However, when meropenem is recommended for individuals with neuromelioidosis and when ceftazidime cannot be used due to allergy, adverse drug reactions, or the organism’s resistance, transitioning patients onto OPAT is challenging. Meropenem undergoes considerable degradation above room temperature and is therefore difficult to administer as a continuous infusion in the tropical locations where the melioidosis is usually encoutered.[1] This means that patients with preserved renal function who require meropenem for the intensive intravenous phase of therapy usually stay in hospital to receive intermittently dosed therapy to complete their treatment. Even in Australia’s well-resourced healthcare setting, this creates additional strain on hospitals, particularly as most cases of melioidosis are concentrated during the warmer, wet season when other seasonal infections are also common.[5]
Extended infusions of β-lactam antibiotics are now recommended to improve attainment of PK/PD targets in critically ill inpatients.[6,7] However, experience with continuous meropenem infusions in stable patients and in the community is limited. Some cases series describing meropenem infusers as OPAT have reported adequate plasma concentrations and excellent clinical outcomes, but these studies have occurred predominantly in temperate climate settings where annual mean maximum temperatures are <25°C.[8,9,10] In tropical Australia the annual mean maximum temperature is 29oC year-round and is >30oC in the warmer wet season when most cases of melioidosis are seen.[11] The impact of these warmer temperatures on the clinical outcomes of individuals with melioidosis receiving meropenem as a continuous infusion in a community setting has not been defined.
In this study we examined the clinical course of patients with melioidosis who received twice daily meropenem via elastomeric infusers as OPAT in tropical Australia. It was hoped that this would provide data to inform the clinical management of individuals requiring meropenem for the intensive phase of their intravenous therapy.

Methods

The study was approved by the Far North Queensland Human Research Ethics Committee (HREC/15/QCH/46-977).
We reviewed all patients diagnosed with culture-confirmed B. pseudomallei infection at Cairns Hospital in northern Australia between 1st January 2016 and 30th April 2026, a period of prospective data collection. We reviewed each patient’s electronic medical record and recorded their demographics, comorbidities, presentation, treatment and clinical course as described previously.[12] For those that received intravenous meropenem as a continuous infusion as OPAT, we documented the rationale for the meropenem use and the B. pseudomallei meropenem MIC defined by ETEST (EUCAST). We also recorded the patients’ creatinine clearance, their continuous infusion dose, the duration of OPAT, any random free (unbound) serum meropenem concentration results and any dosage adjustments that occurred.

Results

There were 560 patients with melioidosis during the study period, 9 (2%) of whom received meropenem as a continuous infusion as OPAT (Table 1). Of these 9 patients, 6 had an ADR to ceftazidime, 1 had a ceftazidime resistant organism, 1 had neuromelioidosis and 1 had relapsed disease. The median (range) B. pseudomallei meropenem MIC was 1 (0.5-1) mg/L.
All patients received twice daily elastomeric infusers which contained meropenem in 0.9% normal saline. The infusers were not buffered, had a volume of 120 ml and an infusion rate of 10 ml per hour. The maximum concentration was 25 mg/ml per infuser. Initial dosing was 1.5g 12-hourly in 5 patients and 3g 12-hourly in 4 patients. The median (range) duration of meropenem treatment via OPAT was 24 (6-47) days. The initial median (range) meropenem random concentration was 6.5 (2.3-18.1) mg/L.
Therapeutic drug monitoring (TDM) led to an increased meropenem dose in 2 patients. This included one patient who was administered a dose of 4.5 g 12-hourly which was administered using 2 separate 120 mL elastomeric infusers every 12 hours to maintain a concentration below 25 mg/ml in each infuser. One patient was changed from meropenem to ceftazidime after 9 days due to a rising serum eosinophil count which was attributed to meropenem although there were no end-organ sequelae; there were no other ADRs. All patients completed oral eradication therapy, and none had disease recurrence at a median (interquartile range) follow up of 36 (14-40) months from completion of their intensive phase.

Discussion

Meropenem administered via twice daily elastomeric infusers as OPAT is a viable option in select patients with melioidosis. This therapeutic strategy, which can be further optimised with TDM, can result in excellent clinical outcomes and can expedite hospital discharge. Transitioning patients to OPAT is appreciated by patients, avoids hospital-acquired complications and, in an era of finite health resources, is highly cost-effective. Early conversion to OPAT is of particular importance in melioidosis as these patients frequently require a prolonged course of intravenous antibiotics to prevent potentially life-threatening recurrence.[4]
The stability of ceftazidime in elastomeric infusers means that most patients receive this antibiotic as part of their care, an approach that results in excellent outcomes. However, around 10% of people who receive ceftazidime will have an ADR.[13] Alternative agents that have in vitro activity against B. pseudomallei include piperacillin-tazobactam, cefiderocol, tigecycline and sulbactam-durlobactam but there are no clinical data to support their use in vivo.[1] Administering meropenem as a continuous infusion as OPAT is therefore an attractive therapeutic alternative.
However, concerns about meropenem’s degradation in solution, which is influenced by concentration, time and temperature, have limited uptake of meropenem as OPAT.[1] One study showed that meropenem diluted to 25mg/ml in 0.9% sodium chloride and stored at 32°C degraded 34% after 24 hours, although in another study meropenem remained stable for 8 hours between 25°C and 35°C.[14,15] In tropical Australia, the annual mean maximum temperatures are >25°C, and exceed 30°C in November-March when most of cases of melioidosis are seen.[5] Therefore twice daily dosing was chosen recognising the greater degradation of meropenem at higher temperatures, however, aside from advising patients to avoid putting their elastomeric infusers in direct sunlight, we implemented no additional measures to keep infusers cool. Only one patient in our cohort required a dose greater than 3 g 12-hourly, and this was overcome by utilising 2 infusers simultaneously to avoid exceeding a concentration >25 mg/ml.
Increased availability of TDM can mitigate some of the concerns about stability and degradation. The optimal dosing of meropenem for use in continuous infusions is incompletely defined, but TDM can inform dose changes that ensure the free drug concentration in plasma remains >4 x MIC.[16] Most first episode Australian B. pseudomallei isolates have a meropenem MIC ≤1 mg/L making target levels attainable with continuous infusions while maintaining safety.[17] Only one patient in our cohort had an ADR attributed to meropenem when it was administered as a continuous infusion as OPAT. Doses higher than 3g 12-hourly may be required to treat organisms with MICs ≥ 2 mg/L, although the safety of this approach is uncertain.
Our retrospective study is limited by reliance on medical record documentation. Random meropenem serum concentrations are collected from a peripheral venepuncture, however when patients decline phlebotomy, a sample from their peripheral inserted central catheter (PICC) is collected. This could result in a higher meropenem concentration; however, our standard protocol involves discarding the first 10 ml of blood prior to sample collection. In our OPAT, patients are seen twice daily in their own home by experienced nursing staff to connect their meropenem infusers. Every effort is made to ensure this occurs 12-hourly, but issues with travel over a 50 km distance and the accommodation of other patients in a busy service may result in small timing variations when changing infusers. Our ability to provide this service is enabled by Australia’s well-resourced healthcare which may not be possible in many other locations where melioidosis is endemic. Additionally, the relatively low meropenem MICs seen in B. pseudomallei isolates in our region may differ in other geographical areas and our approach may not be transferrable.
Twice daily meropenem continuous infusions administered as OPAT are an alternative treatment option for select patients with melioidosis where ceftazidime use is not possible, even in hot, tropical settings where most cases of melioidosis occur. Increasing availability and utilisation of TDM can overcome concerns regarding stability and degradation in extended infusions and ensure that adequate serum concentrations are obtained. Utilisation of meropenem in OPAT allows patients to be treated comfortably at home, avoiding prolonged hospital admissions and alleviating pressure on finite inpatient hospital resources.

Conflict of interest statement

The authors have no conflicts of interest to declare

Funding statement

This study received no specific funding

Data availability statement

Data cannot be shared publicly because of the Queensland Public Health Act 2005. Data are available from the Far North Queensland Human Research Ethics Committee (contact via email FNQ_HREC@health.qld.gov.au) for researchers who meet the criteria for access to confidential data.

References

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Table 1. Clinical characteristics and results of patients receiving meropenem continuous infusions via OPAT.
Table 1. Clinical characteristics and results of patients receiving meropenem continuous infusions via OPAT.
Patient Age, sex, weight Calculated creatinine clearance a Site of Infection Duration of IV treatment (weeks) Meropenem OPAT duration Meropenem MIC b Rationale for
meropenem
use in OPAT		 Initial meropenem OPAT dose Initial serum meropenem concentration (mg/L) Dose changed due to Meropenem TDM
1 29M, 78kg 107 Bacteraemia, pulmonary, prostate and renal abscess, neuromelioidosis 8 39 days 1 Neuromelioidosis 3g 12-hourly 9.6c No
2 56F, 82kg 112 Bacteraemia, septic arthritis, osteomyelitis 6 34 days 1 Resistance to ceftazidime (MIC 64 mg/L) 3g 12-hourly 18.1 Nod
3 29M, 115kg 203 Bacteraemia, pulmonary, liver abscess, myositis, osteomyelitis 6 32 days 1 Relapsed disease e 3g 12-hourly 2.3 Yes – increase to 4.5g 12-hourlyf
4 76F, 87kg 51 Urinary, renal abscess 4 25 days 1 Ceftazidime ADR (parageusia) & recurrence of collection 1.5g 12-hourly 2.4 Yes – increase to 3g 12-hourlyg
5 55M, 130kg 162 Bacteraemia, prostate abscess 4 10 days 1 Ceftazidime ADR (vasculitic rash) 3g 12-hourly 3.2 No
6 17F, 98kg 134h Thigh abscess 2 11 days 1 Ceftazidime ADR (urticarial rash) 1.5g 12-hourly - N/A
7 63F, 56kg 50 Bacteraemia, pulmonary, Peritoneal 4 6 days 0.5 Ceftazidime ADR (rash) 1.5g 12-hourly - N/A
8 60F, 71kg 45 Recurrent pulmonary disease 8i 47 days 1 Ceftazidime ADR (rash) 1.5g 12-hourly 6.5 No
9 39F, 69kg 100 Bacteraemia, pulmonary 4 9 days 1 Ceftazidime ADR (LFT derangement, eosinophilia) 1.5g 12-hourly 10.2 Noj
IV, intravenous; OPAT, outpatient parenteral antimicrobial therapy; TDM, therapeutic drug monitoring; TMP/SMX, trimethoprim/sulfamethoxazole; ADR, adverse drug reaction, LFT, liver function test a Creatinine clearance (calculated by Cockroft-Gault equation) b Minimum inhibitory concentration of B. pseudomallei isolates for meropenem as defined by EUCAST; if multiple isolates, highest MIC reported. c Subsequent serum meropenem drug levels taken during treatment ranged from 5.3-13.2mg/L. d Subsequent serum meropenem drug levels taken during treatment ranged from 7.4-19.8mg/L. e Two relapses with progressive multiorgan involvement with possibility of non-adherence to initial oral eradication phase. f Subsequent serum meropenem drug levels taken post dose increase – 6.9 and 12.9mg/L. g Subsequent serum meropenem drug levels taken post dose increase – 3.0 and 4.4mg/L. h Glomerular filtration rate calculated using the revised Schwartz equation. i Extended intravenous course due to recrudescence of disease, doxycycline resistant isolate and patient unable to tolerate TMP/SMX due to previous acute kidney injury. j Peripheral blood eosinophilia initially attributed to ceftazidime but continued to increase to 4.3 x 109/L following change to meropenem; clinical decision to change back to ceftazidime.
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