•Outpatient parenteral antibiotic therapy (OPAT) can be used safely in the management of infective endocarditis (IE).•IE caused by high-virulence organisms such as Staphylococcus aureus can be ...managed with OPAT.•Patients with prosthetic valve IE can be considered for OPAT.•OPAT has the potential to reduce the impact of IE on over-burdened health systems.
We examined the safety and clinical outcomes of outpatient parenteral antibiotic therapy (OPAT) for patients with infective endocarditis (IE) in Christchurch, New Zealand.
Demographic and clinical data were collected from all adult patients treated for IE over 5 years. Outcomes were stratified by receipt of at least partial OPAT vs entirely hospital-based parenteral therapy.
There were 172 episodes of IE between 2014 and 2018. OPAT was administered in 115 cases (67%) for a median of 27 days after a median of 12 days of inpatient treatment. In the OPAT cohort, viridans group streptococci were the commonest causative pathogens (35%) followed by Staphylococcus aureus (25%) and Enterococcus faecalis (11%). There were six (5%) antibiotic-related adverse events and 26 (23%) readmissions in the OPAT treatment group. Mortality in OPAT patients was 6% (7/115) at 6 months and 10% (11/114) at 1 year and for patients receiving wholly inpatient parenteral therapy was 56% (31/56) and 58% (33/56), respectively. Three patients (3%) in the OPAT group had a relapse of IE during the 1-year follow-up period.
OPAT can be used safely in patients with IE, even in selected cases with complicated or difficult-to-treat infections.
Outpatient parenteral antimicrobial therapy (OPAT) has become an established option for management infections requiring intravenous therapy. As the uptake of OPAT has increased, the clinical ...governance has changed and is now managed via virtual clinics and increased use of district nurses in addition to specialist outpatient review. The aim of this study was to report the characteristics, diagnoses, treatment and outcomes of patients managed by the service over 12 months in 2015/6 and compared these features with those of patients treated with OPAT in 1999.
Cases for 2015/6 were identified from the OPAT service database which records prospectively all information on diagnosis, antibiotic choice and duration of treatment, complications and requirement for review by the ID physicians and OPAT nurses prospectively. The outcomes, complications and readmissions were found by reviewing computerised records of Christchurch Hospital. All results were entered into a Microsoft® Excel database for analysis. Statistical analyses were performed using OpenEpi software. Data for 1999 was taken from an earlier publication.
OPAT treatment in 12 months from 1 July 2015 was administered 407 times to 385 patients, which represented a 2.7 times increase in treatment courses than in 1999. The median age was 55 years in 1999 and 61 in 2015/6. There was a substantial increase in the proportion of bone and joint, abdominal and urinary tract infections but a fall in cellulitis and soft tissue infection. The number and proportion of patients treated with broad spectrum agents including piperacillin + tazobactam, ceftriaxone and carbapenems increased from 1% in 1999 to 20% in 2015/6. Unplanned readmission to hospital increased from 15 (10%) in 1999 to 62 patients (15%) in 2015/6. The most common reason for readmission in 2015/6 was for ongoing symptoms or progression of the infection requiring OPAT. Eight patients (2%) required readmission from adverse reactions to antimicrobial therapy. Two patients on palliative care died while on OPAT and 35 (9%) within 12 months of the index admission.
OPAT use has increased and is used to treat patients with comorbidities, who are older, and with a different case-mix than 1999. Safety has not been compromised but the risk of treatment failure has increased. A better understanding of the reasons for treatment failure would improve patient selection and management with OPAT.
Aims
Oral flucloxacillin may be coadministered with probenecid to reduce flucloxacillin clearance and increase attainment of pharmacokinetic–pharmacodynamic (PK/PD) targets. The aims of this study ...were to develop a population PK model of free flucloxacillin when administered orally with probenecid, and to identify optimal dosing regimens for this combination.
Methods
We performed a prospective observational study of adults (45 participants) treated with oral flucloxacillin 1000 mg and probenecid 500 mg 8‐hourly for proven or probable staphylococcal infections. Steady‐state mid‐dose‐interval flucloxacillin measurements (45 concentrations) were combined with existing data from a crossover study of healthy participants receiving flucloxacillin with and without probenecid (11 participants, 363 concentrations). We developed a population pharmacokinetic model of free flucloxacillin concentrations within Monolix, and used Monte Carlo simulation to explore optimal dosing regimens to attain PK/PD targets proposed in the literature (free drug time above minimum inhibitory concentration).
Results
Flucloxacillin disposition was best described by a 1‐compartment model with a lag time and first‐order absorption. Free flucloxacillin clearance depended on probenecid, allometrically‐scaled fat free mass (FFM) and estimated glomerular filtration rate (eGFR). Predicted PK/PD target attainment was suboptimal with standard dosing regimens with flucloxacillin alone, but substantially improved in the presence of probenecid.
Conclusion
The simulation results reported can be used to identify dose regimens that optimise flucloxacillin exposure according to eGFR and FFM. Patients with higher FFM and eGFR may require the addition of probenecid and 6‐hourly dosing to achieve PK/PD targets. The regimen was well‐tolerated, suggesting a potential for further evaluation in controlled clinical trials to establish efficacy.
•Therapeutic drug monitoring can improve the probability of pharmacological target attainment.•Standard dosing of flucloxacillin and cefazolin may result in below target plasma levels.•Below target ...levels occurred more frequently in patients receiving flucloxacillin than cefazolin.•Patient characteristics may help to predict those at risk of below target plasma levels.
The proportion of patients with invasive methicillin-susceptible Staphylococcus aureus (MSSA) infection who achieve target concentrations of flucloxacillin or cefazolin with standard dosing regimens is uncertain. This study measured drug concentrations in a prospective cohort of patients with invasive S. aureus infections to determine the frequency of target concentration attainment, and risk factors for failure to achieve target concentrations.
Unbound flucloxacillin and cefazolin plasma concentrations were measured at the midpoint between intravenous doses. Adequate and optimal targets were defined as an unbound plasma concentration of ≥1 and ≥2 times the minimum inhibitory concentration (MIC) (flucloxacillin 0.5 mg/L, cefazolin 2 mg/L), respectively (50%fT≥1MIC, 50%fT≥2MIC).
There were 50 patients in each of the flucloxacillin and cefazolin groups. Eighty-five (85%) patients met the target of 50%fT≥2MIC and 95 (95%) patients met the target of 50%fT≥1MIC. The median unbound flucloxacillin concentration was 2.6 mg/L interquartile range (IQR) 1.0–8.1. The median unbound cefazolin concentration was 15.4 mg/L (IQR 8.8–28.2). A higher proportion of patients in the flucloxacillin group failed to achieve the optimal target compared with the cefazolin group 13 (26%) vs 2 (4%); P=0.002. Younger age and higher creatinine clearance were associated with lower plasma concentrations.
Standard dosing of flucloxacillin and cefazolin in the treatment of invasive MSSA infections may not achieve target plasma concentrations for a subgroup of patients. Measuring drug concentrations identifies this subgroup and facilitates dose individualization.
Background and objective
Legionella longbeachae is a predominant cause of Legionnaires' disease in some parts of the world, particularly in Australasia. Clinical reports of L. longbeachae infection ...are limited to case reports or small case series, and culture‐confirmed cases.
Methods
We reviewed the clinical characteristics and outcomes of L. longbeachae pneumonia in a large case series from Christchurch, New Zealand during a 4‐year period when both PCR and cultures were used as routine diagnostic tools for Legionnaires' disease. Cases of Legionella pneumophila pneumonia were reviewed for comparison.
Results
A total of 107 cases of L. longbeachae infection were identified by PCR and/or culture. The median age was 65 years (range 25–90 years), 63% were male, and most became unwell during spring or summer. Presenting clinical features were similar to those reported for community‐acquired pneumonia, with headache, myalgia and diarrhoea being common. Elevated C‐reactive protein, hyponatraemia and abnormal liver function tests were also common. History of productive cough, involvement of both lungs, and high bacterial load were independently associated with culture of Legionella from lower respiratory samples. One quarter required intensive care unit admission, and 5% died. Among patients given antimicrobial therapy before admission, those given agents without anti‐Legionella activity were more likely to be admitted to the intensive care unit. Limited comparisons were made with the 19 L. pneumophila cases over the same time period.
Conclusion
Characteristics of L. longbeachae pneumonia are broadly similar to those reported for community‐acquired pneumonia from a variety of other populations, except for the spring/summer seasonality.
Descriptions of Legionella longbeachae infection are limited to case reports or small case series. We reviewed the clinical characteristics of 107 cases of L. longbeachae pneumonia from a single centre. Characteristics of L. longbeachae pneumonia are similar to those reported for community‐acquired pneumonia in general except for the spring/summer seasonality.
Reducing the vulnerability of coastal communities to marine climate change requires that communities have some intrinsic capacity to adapt. To assist adaptation planning and the implementation of ...adaptation strategies, identifying barriers and enablers to adaptation is important. Adaptive capacity, resource dependence, local climate change exposure and biological sensitivity were used to assess socioeconomic vulnerability to climate change in three Australian coastal communities: St Helens, Tasmania; Bowen, Queensland; and Geraldton, Western Australia. Higher adaptive capacity was associated with larger population size (i.e., Geraldton) whereas greater resource dependence, and lower human and natural capital were associated with smaller populations (St Helens and Bowen). Socioeconomic vulnerability was greatly influenced by climate exposure and sensitivity with the moderately sized Bowen having the highest socioeconomic vulnerability to climate change. Adaptation strategies that utilized available assets, improved adaptive capacity, or reduced socioeconomic vulnerability were identified in partnership with local communities, including increased and diversified employment opportunities, the re-establishment of local fish markets, and improved education and communication. The level of resources, or “capitals,” available to communities can indicate where barriers and enablers to adaptation exist. Identified barriers to adaptation included a heavy reliance on one sector for employment and a lack of physical capital. We demonstrate that knowledge of intrinsic community characteristics can be beneficial for prioritizing adaptation actions to reduce socioeconomic vulnerability to marine climate change.
To assess a persuasive multimodel approach to decreasing unnecessary intravenous (IV) clarithromycin use for community-acquired pneumonia (CAP) in Canterbury District Health Board (CDHB) hospitals.
...In December 2013, CDHB guidelines for empiric treatment of CAP changed to prioritise oral azithromycin over IV clarithromycin. The multimodel approach we used to implement this change included obtaining stakeholder agreement, improved guidelines access, education and pharmacist support. The impact of the intervention was evaluated by comparing macrolide usage and expenditure for the four years pre- and post-intervention.
Mean annual clarithromycin IV use decreased by 72% from 6.4 to 1.8 defined daily doses (DDDs) per 1,000 occupied bed days (OBDs) post-intervention, while oral azithromycin increased by 833% (4.2 to 39.2 DDDs per 1,000 OBDs). Concurrently, oral clarithromycin use decreased by 91% (32.9 to 2.9 DDDs per 1,000 OBDs), and roxithromycin by 71% (17.0 to 5.0 DDDs per 1,000 OBDs). Mean annual total macrolide use decreased by 21% (68.2 to 53.9 DDDs per 1,000 OBDs), while expenditure decreased by 69% mainly through avoided IV administration.
A persuasive multimodel approach to support adoption of CAP guidelines produced a sustained decrease in IV clarithromycin use, which may have clinical benefits such as reduced occurrence of catheter-related complications.
•Nephrotoxicity occurred in only 3.4% of outpatients on vancomycin infusions.•Previous studies reported an incidence of 15–17%.•Lower incidence in this study may be due to more frequent ...monitoring.•Improved dosing strategies may further reduce the risk of acute kidney injury.
Vancomycin continuous infusion (VCI) is used to treat serious Gram-positive infections in outpatients. This study was conducted to retrospectively investigate the rate of nephrotoxicity and associated risk factors in out-patients on VCI between May 2013 and November 2018. Vancomycin concentration was monitored twice-weekly to ensure adequate concentrations while avoiding high concentrations linked to nephrotoxicity (a rise in serum creatinine of ≥50% or 44 µmol/L from baseline). The likelihood of developing nephrotoxicity was evaluated using multivariable logistic regression. The 223 patients treated had a mean (standard deviation) age of 61 (16.7) years, baseline serum creatinine of 83.9 (21.2) µmol/L and estimated glomerular filtration rate (eGFR) of 80.6 (20.1) mL/min/1.73m2. Most patients (66%) were treated for bone and joint infections. Eight patients (3.6%) developed nephrotoxicity. In the most parsimonious model, nephrotoxicity was independently associated with an increased median (interquartile range) weighted-average serum vancomycin concentration (28.0 24.3–32.6 vs. 22.4 20.2–24.5 mg/L; odds ratio OR 1.25; 95% confidence interval 95% CI 1.09–1.46; P<0.002) and Charlson co-morbidity index (OR 1.62; 95% CI 1.07–2.47; P=0.02). Post-hoc analysis identified 26 patients with a lower nephrotoxicity threshold (rise in serum creatinine of ≥30% or 27 μmol/L). Independent predictors of nephrotoxicity in this group were an increased weighted-average vancomycin concentration, diabetes, con-gestive heart failure and exposure to non-loop diuretics. The nephrotoxicity rate during VCI in this study was lower than previously reported (3.6% vs 15.0–17.0%). Reducing the weighted-average serum vancomycin concentration may reduce nephrotoxicity while maintaining efficacy.
To determine the nature and appropriateness of antimicrobial prescribing in adult inpatients at Canterbury District Health Board (CDHB).
Multidisciplinary teams collected clinical details for all ...adult inpatients on antimicrobial therapy at three CDHB facilities (~1,100 beds) and made standardised assessments based on the Australian National Antimicrobial Prescribing Survey (http://naps.org.au) against local guidelines and national funding criteria.
Antimicrobial therapy was prescribed to 42% of inpatients (322/760), usually to treat infections 377/480 prescriptions (79%), with amoxicillin+clavulanic acid the agent most commonly prescribed 72/480 prescriptions (15%). Of assessable prescriptions, 74% (205/278) were guideline compliant, 98% (469/480) were funding criteria compliant, and 83% (375/451) were appropriate clinically. Prescriptions for the most common indications-surgical prophylaxis 66/480 (14%) and community-acquired pneumonia 56/480 (12%)-were often non-compliant with guidelines (32% and 41%, respectively) and inappropriate (18% and 21%, respectively). Overall, the indication was documented in 353/480 (74%) prescriptions, the review/stop date documented in 145/480 (30%) prescriptions, and surgical prophylaxis stopped within 24 hours in 53/66 (80%) prescriptions.
Most antimicrobial prescriptions were appropriate and complied with guidelines. Compliance with key quality indicators (indication documented, review/stop date documented, and surgical prophylaxis ceased within 24 hours) were well below target (>95%) and needs improvement.
Diaporthe phaseolorum is a fungal plant parasite that has rarely been described as causing invasive human disease. We report a case of human soft tissue infection with Diaporthe phaseolorum in a ...heart transplant patient with end-stage renal failure in New Zealand.
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