Implementation of a quality improvement strategy to optimise the management of community acquired pneumonia in a rural health setting.

PROBLEM: In Australia, inappropriate prescribing of antimicrobials is higher in rural and regional areas than in major city hospitals. Inappropriate prescribing is defined as the prescription of antimicrobial agents that do not adhere to guidelines in terms of type of antimicrobial chosen, dose and/or duration or are deemed unnecessary. A review of antimicrobial prescribing in a Queensland rural Hospital and Health Service (HHS) identified that respiratory infections were an area for potential improvement. SETTING: The study was performed in a rural HHS in Queensland. KEY MEASURES FOR IMPROVEMENT: Appropriateness of antimicrobial prescribing for baseline and post-implementation phases of the study was evaluated according to Therapeutic Guidelines: antibiotic recommendations for community acquired pneumonia (CAP). STRATEGIES FOR CHANGE: Quality improvement strategy to implement a multifaceted package of interventions for CAP. EFFECTS OF CHANGE: Post-implementation, overall appropriateness of antimicrobial prescribing improved and there was a decrease in duration of antimicrobial therapy. LESSONS LEARNT: A quality improvement strategy to implement a multifaceted package of interventions for CAP has shown to be acceptable and effective in improving the antimicrobial prescribing in a rural setting. Our findings highlight the importance of utilising a multifaceted package of interventions which can be tailored to the prescribers and the patients at hand. It is also valuable to engage with local clinicians to promote the optimal management of common infections in the rural setting.

Reducing antibiotic prescribing in general practice in Australia: a cluster randomised controlled trial of a multimodal intervention.

BACKGROUND: The health and economic burden of antimicrobial resistance (in Australia is significant. Interventions that help guide and improve appropriate prescribing for acute respiratory tract infections in the community represent an opportunity to slow the spread of resistant bacteria. Clinicians who work in primary care are potentially the most influential health care professionals to address the problem of antimicrobial resistance, because this is where most antibiotics are prescribed. METHODS: A cluster randomised trial was conducted comparing two parallel groups of 27 urban general practices in Queensland, Australia: 13 intervention and 14 control practices, with 56 and 54 general practitioners (GPs), respectively. This study evaluated an integrated, multifaceted evidence-based package of interventions implemented over a 6-month period. The evaluation included quantitative and qualitative components, and an economic analysis. RESULTS: A multimodal package of interventions resulted in a reduction of 3.81 prescriptions per GP per month. This equates to 1280.16 prescriptions for the 56GPs in the intervention practices over the 6-month period. The cost per prescription avoided was A$148. The qualitative feedback showed that the interventions were well received by the GPs and did not impact on consultation time. Providing GPs with a choice of tools might enhance their uptake and support for antimicrobial stewardship in the community. CONCLUSIONS: A multimodal package of interventions to enhance rational prescribing of antibiotics is effective, feasible and acceptable in general practice. Investment in antimicrobial stewardship strategies in primary care may ultimately provide the important returns for public health into the future.

Improving paediatric antimicrobial stewardship in remote and regional Queensland hospitals: development and qualitative evaluation of a tailored intervention for intravenous-to-oral antibiotic switching.

OBJECTIVES: Timely intravenous-to-oral antibiotic switching for children is important for paediatric antimicrobial stewardship (AMS). However, low decision-making confidence and fragmentation of patient care can hamper implementation, with difficulties heightened regionally where AMS programmes for children are lacking. The aim of this study was to develop and evaluate user-led creation and implementation of an intervention package for early intravenous-to-oral switching at regional hospitals in Queensland, Australia. DESIGN: Guided by theory, a four-phase approach was used to: (1) develop multifaceted intervention materials; (2) review materials and their usage through stakeholders; (3) adapt materials based on user-feedback and (4) qualitatively evaluate health workers experiences at 6 months postintervention. SETTING: Seven regional hospitals in Queensland, Australia. PARTICIPANTS: Phase 2 included 15 stakeholders; health workers and patient representatives (patient-guardians and Indigenous liaison officers). Phase 4 included 20 health workers across the seven intervention sites. RESULTS: Content analysis of health worker and parent/guardian reviews identified the 'perceived utility of materials' and 'possible barriers to use'. 'Recommendations and strategies for improvement' provided adjustments for the materials that were able to be tailored to individual practice. Postintervention interviews generated three overarching themes that combined facilitators and barriers to switching: (1) application of materials, (2) education and support, and (3) team dynamics. Overall, despite difficulties with turnover and problems with the medical hierarchy, interventions aided and empowered antibiotic therapy decision-making and enhanced education and self-reflection. CONCLUSIONS: Despite structural barriers to AMS for switching from intravenous-to-oral antibiotics in paediatric patients, offering a tailored multifaceted intervention was reported to provide support and confidence to adjust practice across a diverse set of health workers in regional areas. Future AMS activities should be guided by users and provide opportunities for tailoring tools to practice setting and patients' requirements.

Evaluating Mono- and Combination Therapy of Meropenem and Amikacin against Pseudomonas aeruginosa Bacteremia in the Hollow-Fiber Infection Model.

Debate continues as to the role of combination antibiotic therapy for the management of Pseudomonas aeruginosa infections. We studied the extent of bacterial killing by and the emergence of resistance to meropenem and amikacin as monotherapies and as a combination therapy against susceptible and resistant P. aeruginosa isolates from bacteremic patients using the dynamic in vitro hollow-fiber infection model. Three P. aeruginosa isolates (meropenem MICs of 0.125, 0.25, and 64 mg/L) were used, simulating bacteremia with an initial inoculum of ~1 × 105 CFU/mL and the expected pharmacokinetics of meropenem and amikacin in critically ill patients. For isolates susceptible to amikacin and meropenem (isolates 1 and 2), the extent of bacterial killing was increased with the combination regimen compared with the killing by monotherapy of either antibiotic. Both the combination and meropenem monotherapy were able to sustain bacterial killing throughout the 7-day treatment course, whereas regrowth of bacteria occurred with amikacin monotherapy after 12 h. For the meropenem-resistant P. aeruginosa isolate (isolate 3), only the combination regimen demonstrated bacterial killing. Given that tailored antibiotic regimens can maximize potential synergy against some isolates, future studies should explore the benefit of combination therapy against resistant P. aeruginosa. IMPORTANCE Current guidelines recommend that aminoglycosides should be used in combination with ß-lactam antibiotics as initial empirical therapy for serious infections, and otherwise, patients should receive ß-lactam antibiotic monotherapy. Given the challenges associated with studying the clinical effect of different antibiotic strategies on patient outcomes, useful data for subsequent informed clinical testing can be obtained from in vitro models like the hollow-fiber infection model (HFIM). Based on the findings of our HFIM, we propose that the initial use of combination therapy with meropenem and amikacin provides some bacterial killing against carbapenem-resistant P. aeruginosa isolates. For susceptible isolates, combination therapy may only be of benefit in specific patient populations, such as critically ill or immunocompromised patients. Therefore, clinicians may want to consider using the combination therapy for the initial management and ceasing the aminoglycosides once antibiotic susceptibility results have been obtained.

Where to from here? Identifying and prioritising future directions for addressing drug-resistant infection in Australia.

BACKGROUND: The Australian National Antimicrobial Resistance Strategy calls for a collaborative effort to change practices that have contributed to the development of drug-resistance and for implementation of new initiatives to reduce antibiotic use. METHODS: A facilitated workshop was undertaken at the 2019 National Australian Antimicrobial Resistance Forum to explore the complexity of antimicrobial stewardship (AMS) implementation in Australia and prioritise future action. Participants engaged in rotating rounds of discussion using a world café format addressing six topics relating to AMS implementation. Once all tables had discussed all themes the discussion concluded and notes were summarised. The documents were independently openly coded by two researchers to identify elements relating to the implementation of antimicrobial stewardship. RESULTS: There were 39 participants in the facilitated discussions, including pharmacists, infectious disease physicians, infection prevention nurses, and others. Participants discussed strategies they had found successful, including having a regular presence in clinical areas, adapting messaging and implementation strategies for different disciplines, maintaining positivity, and being patient-focused. Many of the recommendations for the next step involved being patient focussed and outcomesdriven. This involves linking data to practice, using patient stories, using data to celebrate wins and creating incentives. DISCUSSION: Recommendations from the workshop should be included in priority setting for the implementation of AMS initiatives across Australia.

Oral or intravenous antibiotics?

Intravenous antibiotics are overused in hospitals. Many infections can be managed with oral antibiotics Oral antibiotics avoid the adverse effects of intravenous administration. They are also usually less expensive When intravenous antibiotics are indicated, it may be possible to switch to oral therapy after a short course. There are guidelines to aid the clinician with the timing of the switch so that there is no loss of efficacy Infections that may be suitable for a short course of intravenous antibiotic include pneumonia, complicated urinary tract infections, certain intra-abdominal infections, Gram-negative bacteraemia, acute exacerbations of chronic lung disease, and skin and soft tissue infections Bone and joint infections and infective endocarditis are managed with prolonged courses of intravenous antibiotics. However, there is research looking at the feasibility of an earlier switch to oral antibiotics in these conditions

Evaluation of quick sequential organ failure assessment and systemic inflammatory response syndrome in patients with gram negative bloodstream infection.

BACKGROUND: The quick sequential organ failure assessment (qSOFA) score predicts mortality in patients with suspected infection. We sought to understand how well qSOFA and the Systemic Inflammatory Response Syndrome (SIRS) criteria predict gram negative bacteraemia. METHODS: We prospectively evaluated 99 patients with gram negative bloodstream infection from a single tertiary centre. We assessed the utility of SIRS and qSOFA for their rate of positivity and association with early delivery of antibiotics (<3 h). RESULTS: The SIRS criteria had the highest positivity rate amongst patients with gram negative bacteraemia (85%) compared to the qSOFA criteria (25%) on the day of first positive culture. Positive SIRS criteria was the only score associated with delivery of antibiotics within 3 h (Relative risk 3.5, 95% Confidence interval 1.3 to 12.5, p = < 0.02). CONCLUSION: In patients with gram negative bloodstream infection SIRS criteria was the most common positive risk score and had a higher association with early delivery of antibiotics when compared to qSOFA.

An underutilised resource for Antimicrobial Stewardship: a 'snapshot' of the community pharmacists' role in delayed or 'wait and see' antibiotic prescribing.

OBJECTIVES: Various strategies have been implemented in primary care to address the inappropriate use of antibiotics, with varying degrees of success. One such intervention is delayed or 'wait and see' prescribing, where the prescriber indicates to wait a few days before dispensing the antibiotic. The aim of this study was to explore community pharmacists' perceptions and practice experiences with delayed antibiotic prescribing. METHODS: An online survey was advertised in two professional pharmacy organisations' e-newsletters for community and internship pharmacists in Queensland, Australia, from January to April 2016. KEY FINDINGS: We received 120 responses. 103 (86%) worked in a community pharmacy. Sixty per cent of the respondents would not dispense the delayed antibiotic prescription if a patient presented to the pharmacy within 24 h of seeing a doctor. Instead, they would advise the patient to wait and fill the prescription if they are not improving. CONCLUSION: The concept of delayed or a 'wait and see' antibiotic prescription was well received by the participating community pharmacists. These healthcare professionals are well placed to be effective stewards of antibiotics and can play an important role in collaboration with other healthcare professionals to optimise the quality use of antibiotics in primary care.

Antibiotic duration and timing of the switch from intravenous to oral route for bacterial infections in children: systematic review and guidelines.

Few studies are available to inform duration of intravenous antibiotics for children and when it is safe and appropriate to switch to oral antibiotics. We have systematically reviewed antibiotic duration and timing of intravenous to oral switch for 36 paediatric infectious diseases and developed evidence-graded recommendations on the basis of the review, guidelines, and expert consensus. We searched databases and obtained information from references identified and relevant guidelines. All eligible studies were assessed for quality. 4090 articles were identified and 170 studies were included. Evidence relating antibiotic duration to outcomes in children for some infections was supported by meta-analyses or randomised controlled trials; in other infections data were from retrospective series only. Criteria for intravenous to oral switch commonly included defervescence and clinical improvement with or without improvement in laboratory markers. Evidence suggests that intravenous to oral switch can occur earlier than previously recommended for some infections. We have synthesised recommendations for antibiotic duration and intravenous to oral switch to support clinical decision making and prospective research.

General Practitioner Antimicrobial Stewardship Programme Study (GAPS): protocol for a cluster randomised controlled trial.

BACKGROUND: There is a strong link between antibiotic consumption and the rate of antibiotic resistance. In Australia, the vast majority of antibiotics are prescribed by general practitioners, and the most common indication is for acute respiratory infections. The aim of this study is to assess if implementing a package of integrated, multifaceted interventions reduces antibiotic prescribing for acute respiratory infections in general practice. METHODS/DESIGN: This is a cluster randomised trial comparing two parallel groups of general practitioners in 28 urban general practices in Queensland, Australia: 14 intervention and 14 control practices. The protocol was peer-reviewed by content experts who were nominated by the funding organization. This study evaluates an integrated, multifaceted evidence-based package of interventions implemented over a six month period. The included interventions, which have previously been demonstrated to be effective at reducing antibiotic prescribing for acute respiratory infections, are: delayed prescribing; patient decision aids; communication training; commitment to a practice prescribing policy for antibiotics; patient information leaflet; and near patient testing with C-reactive protein. In addition, two sub-studies are nested in the main study: (1) point prevalence estimation carriage of bacterial upper respiratory pathogens in practice staff and asymptomatic patients; (2) feasibility of direct measures of antibiotic resistance by nose/throat swabbing. The main outcome data are from Australia's national health insurance scheme, Medicare, which will be accessed after the completion of the intervention phase. They include the number of antibiotic prescriptions and the number of patient visits per general practitioner for periods before and during the intervention. The incidence of antibiotic prescriptions will be modelled using the numbers of patients as the denominator and seasonal and other factors as explanatory variables. Results will compare the change in prescription rates before and during the intervention in the two groups of practices. Semi-structured interviews will be conducted with the general practitioners and practice staff (practice nurse and/or practice manager) from the intervention practices on conclusion of the intervention phase to assess the feasibility and uptake of the interventions. An economic evaluation will be conducted to estimate the costs of implementing the package, and its cost-effectiveness in terms of cost per unit reduction in prescribing. DISCUSSION: The results on the effectiveness, cost-effectiveness, acceptability and feasibility of this package of interventions will inform the policy for any national implementation. TRIAL REGISTRATION: The GAPS trial is registered under the Australian New Zealand Clinical Trials Register, reference number: ACTRN12615001128583 (registered 26/10/2015).

A mixed methods study of the barriers and enablers in implementing antimicrobial stewardship programmes in Australian regional and rural hospitals.

OBJECTIVES: The Australian Commission on Safety and Quality in Health Care released recommendations for antimicrobial stewardship programmes to be established within all Australian healthcare facilities. However, implementation practices are not well defined. The aim of this study was to gain an understanding of factors affecting implementation of antimicrobial stewardship programmes within Australian regional and rural hospitals. METHODS: This study was designed whereby a preliminary quantitative process was used to contribute to a principally qualitative study. Site visits to regional and rural hospitals in Queensland, New South Wales, Victoria and South Australia were planned to assess factors impacting on implementation of antimicrobial stewardship. Subsequently researchers identified issues requiring further exploration with specific key informant interviews and focus group discussions. Data were collected between May and October 2012 and entered into Nvivo10, openly coded and analysed according to mixed methods data analysis principles. RESULTS: Regional and rural hospitals were not conducting many of the recommended activities and seven major themes emerged. The key barriers were perceived to be lack of access to education, resources and specialist support. The enablers were a flatter governance structure, greater sense of pride, desire for success and good internet and tele-health access. CONCLUSIONS: This study helps us to identify where efforts should be focused to facilitate the establishment of antimicrobial stewardship programmes in regional and rural hospitals, by describing the gaps and limitations of current programmes and the major issues currently being faced, providing recommendations to better guide activities that support regional and rural hospitals.

Australia-wide Point Prevalence Survey of Antimicrobial Prescribing in Neonatal Units: How Much and How Good?

BACKGROUND: There is increasing recognition of the threat to neonatal patients from antibiotic resistance. There are limited data on antimicrobial prescribing practices for hospitalized neonates. We aimed to describe antimicrobial use in hospitalized Australian neonatal patients, and to determine its appropriateness. METHODS: Multicentre single-day hospital-wide point prevalence survey in 2012, in conjunction with the Antimicrobial Resistance and Prescribing in European Children study. The appropriateness of antimicrobial prescriptions was also assessed. All patients admitted at 8 am on the survey day, in 6 neonatal units in tertiary children's hospitals across 5 states, were included in an analysis of the quantity and quality of all antimicrobial prescriptions. RESULTS: The point prevalence survey included 6 neonatal units and 236 patients. Of 109 patients (46%) receiving at least 1 antimicrobial, 66 (61%) were being treated for infection, with sepsis the most common indication. There were 216 antimicrobial prescriptions, 134 (62%) for treatment of infection and 82 (38%) for prophylaxis, mostly oral nystatin. Only 15 prescriptions were for targeted as opposed to empirical treatment. Penicillin and gentamicin were the most commonly prescribed antibiotics, with vancomycin third most common. Half of all treated patients were receiving combination antimicrobial therapy. There was marked variation in vancomycin and gentamicin dosing. Overall, few prescriptions (4%) were deemed inappropriate. CONCLUSION: This is the first Australia-wide point prevalence survey of neonatal antimicrobial prescribing in tertiary children's hospitals. The findings highlight positive practices and potential targets for quality improvement.

Australia-wide point prevalence survey of the use and appropriateness of antimicrobial prescribing for children in hospital.

OBJECTIVES: To describe antimicrobial use in hospitalised Australian children and to analyse the appropriateness of this antimicrobial use. DESIGN: Multicentre single-day hospital-wide point prevalence survey, conducted in conjunction with the Antimicrobial Resistance and Prescribing in European Children study. SETTING: Eight children's hospitals across five Australian states, surveyed during late spring and early summer 2012. PATIENTS: Children and adolescents who were inpatients at 8 am on the day of the survey. MAIN OUTCOME MEASURES: Quantity and quality of antimicrobial prescribing. RESULTS: Of 1373 patients, 631 (46%) were prescribed at least one antimicrobial agent, 198 (31%) of whom were < 1 year old. The highest antimicrobial prescribing rates were in haematology and oncology wards (76% [95/125]) and paediatric intensive care units (55% [44/80]). Of 1174 antimicrobial prescriptions, 550 (47%) were for community-acquired infections, 175 (15%) were for hospital-acquired infections and 437 (37%) were for prophylaxis. Empirical treatment accounted for 72% of antimicrobial prescriptions for community-acquired infections and 58% for hospital-acquired infections (395 and 102 prescriptions, respectively). A total of 915 prescriptions (78%) were for antibacterials; antifungals and antivirals were predominantly used for prophylaxis. The most commonly prescribed antibacterials were narrow-spectrum penicillins (18% [164 prescriptions]), ß-lactam-ß-lactamase inhibitor combinations (15% [136]) and aminoglycosides (14% [128]). Overall, 957 prescriptions (82%) were deemed appropriate, but this varied between hospitals (range, 66% [74/112]) to 95% [165/174]) and specialties (range, 65% [122/187] to 94% [204/217]). Among surgical patients, 65 of 187 antimicrobial prescriptions (35%) were deemed inappropriate, and a common reason for this was excessive prophylaxis duration. CONCLUSION: A point prevalence survey is a useful cross-sectional method for quantifying antimicrobial use in paediatric populations. The value is significantly augmented by adding assessment of prescribing quality.

Antimicrobial stewardship activities: a survey of Queensland hospitals.

OBJECTIVE: In 2011, the Australian Commission on Safety and Quality in Health Care (ACSQHC) recommended that all hospitals in Australia must have an Antimicrobial Stewardship (AMS) program by 2013. Nevertheless, little is known about current AMS activities. This study aimed to determine the AMS activities currently undertaken, and to identify gaps, barriers to implementation and opportunities for improvement in Queensland hospitals. METHODS: The AMS activities of 26 facilities from 15 hospital and health services in Queensland were surveyed during June 2012 to address strategies for effective AMS: implementing clinical guidelines, formulary restriction, reviewing antimicrobial prescribing, auditing antimicrobial use and selective reporting of susceptibility results. RESULTS: The response rate was 62%. Nineteen percent had an AMS team (a dedicated multidisciplinary team consisting of a medically trained staff member and a pharmacist). All facilities had access to an electronic version of Therapeutic Guidelines: Antibiotic, with a further 50% developing local guidelines for antimicrobials. One-third of facilities had additional restrictions. Eighty-eight percent had advice for restricted antimicrobials from in-house infectious disease physicians or clinical microbiologists. Antimicrobials were monitored with feedback given to prescribers at point of care by 76% of facilities. Deficiencies reported as barriers to establishing AMS programs included: pharmacy resources, financial support by hospital management, and training and education in antimicrobial use. CONCLUSIONS: Several areas for improvement were identified: reviewing antimicrobial prescribing with feedback to the prescriber, auditing, and training and education in antimicrobial use. There also appears to be a lack of resources to support AMS programs in some facilities. WHAT IS KNOWN ABOUT THE TOPIC?: The ACSQHC has recommended that all hospitals implement an AMS program by 2013 as a requirement of Standard 3 (Preventing and Controlling Healthcare-Associated Infections) of the National Safety and Quality Health Service Standards. The intent of AMS is to ensure appropriate prescribing of antimicrobials as part of the broader systems within a health service organisation to prevent and manage healthcare-associated infections, and improve patient safety and quality of care. This criterion also aligns closely with Standard 4: Medication Safety. Despite this recommendation, little is known about what AMS activities are undertaken in these facilities and what additional resources would be required in order to meet these national standards. WHAT DOES THE PAPER ADD?: This is the first survey that has been conducted of public hospital and health services in Queensland, a large decentralised state in Australia. This paper describes what AMS activities are currently being undertaken, identifies practice gaps, barriers to implementation and opportunities for improvement in Queensland hospitals. WHAT ARE THE IMPLICATIONS FOR PRACTITIONERS?: Several areas for improvement such as reviewing antimicrobial prescribing with feedback to the prescriber, auditing, and training and education in antimicrobial use have been identified. In addition, there appears to be a lack of resources to support AMS programs in some facilities.

Comparing 3 methods of monitoring gentamicin concentrations in patients with febrile neutropenia.

Several nomograms and algorithms have been developed to individualize pharmacokinetic monitoring with their own advantages and disadvantages. This study compared 3 pharmacokinetic methods for predicting doses and monitoring of gentamicin in adult patients with febrile neutropenia. A retrospective study of 75 patients with febrile neutropenia was conducted at the Royal Adelaide Hospital, South Australia. Each patient received a course of once-daily gentamicin and had 2 sets of paired gentamicin serum concentrations. Pharmacokinetic parameters and ensuing doses were compared using 3 pharmacokinetic methods: (1) sequential Bayesian algorithm for gentamicin (SeBA-GEN), (2) Sawchuk-Zaske, and (3) Therapeutic Guidelines: Antibiotic Dose Adjustment Nomogram. The initial median (range) dose of gentamicin administered was 400 (240-640) mg. SeBA-GEN and Sawchuk-Zaske methods recommended similar subsequent gentamicin dose adjustments of 400 (280-640) mg and 400 (280-640) mg, respectively, whereas the Therapeutic Guidelines recommended an increase to 1390 (210-6240) mg. For the Therapeutic Guidelines, 64% of the patients had measured serum gentamicin concentrations that were below the minimum line of the nomogram for the first set of concentrations with only 32% of these patients having an area under the curve value of <70 mg h/L as calculated by SeBA-GEN. The SeBA-GEN method showed a statistically significant increase (68%-77%) in patients attaining the target concentrations of maximum concentration (Cmax) 15-25 mg/L compared with the Sawchuk-Zaske method (72%-65%, P > 0.05). SeBA-GEN also demonstrated greater precision in predicting the area under the curve, Cmax, and minimum concentration (Cmin) compared with the Sawchuk-Zaske method. In conclusion, as the Bayesian approach, that is, SeBA-GEN demonstrated greater precision and more patients were attaining the target concentrations, it is therefore the preferred method for gentamicin monitoring in patients with febrile neutropenia.

Gentamicin and tobramycin in neonates: comparison of a new extended dosing interval regimen with a traditional multiple daily dosing regimen.

Because of a lack of data supporting traditional dosing regimens for aminoglycosides, especially in extremely low-birth-weight infants, the authors developed revised dosing guidelines. The new guidelines increased doses to 5 mg/kg (over traditional doses of 2.5 mg/kg) and lengthened the dosing interval. When results of the two regimens were compared in 120 infants, 26.8% of infants in the traditional dosing group had subtherapeutic levels at <5 microg/mL, whereas only 1.3% of infants in the new practice dosing group were subtherapeutic. With the new dosing practice, serum levels in 1.3% of infants also exceeded the upper therapeutic range of 12 microg/mL. In conclusion, by increasing the dose of aminoglycosides and extending the dosing intervals, therapeutic levels-as defined by a C min <2 microg/mL and a C max of 5 to 12 microg/mL--were obtained significantly more often. In essence the regimen involves once daily dosing for infants <1200 g who are >30 days of age and for infants <1200 g who are >7 days of age. Serum concentrations still need to be monitored where clinically indicated.