Time for first antibiotic dose is not predictive for the early clinical failure of moderate–severe community-acquired pneumonia

A. H. W. Bruns 0 1 2 3 J. J. Oosterheert 0 1 2 3 W. N. M. Hustinx 0 1 2 3 C. A. J. M. Gaillard 0 1 2 3 E. Hak 0 1 2 3 A. I. M. Hoepelman 0 1 2 3 0 C. A. J. M. Gaillard Department of Internal Medicine, Meander Medical Center , Amersfoort, The Netherlands 1 W. N. M. Hustinx Department of Internal Medicine , Diakonessenhuis, Utrecht, The Netherlands 2 A. I. M. Hoepelman Eijkman-Winkler Institute for Microbiology, Infectious Diseases and Inflammation, University Medical Center , Utrecht, The Netherlands 3 E. Hak Department of Epidemiology, University Medical Center , Groningen, The Netherlands The time to first antibiotic dose (TFAD) has been mentioned as an important performance indicator in community-acquired pneumonia (CAP). However, the advice to minimise TFAD to 4 hours (4 h) is only based on database studies. We prospectively studied the effect of minimising the TFAD on the early clinical outcome of moderate-severe CAP. On admission, patients' medical data and TFAD were recorded. Early clinical failure was expressed as the proportion of patients with clinical instability, admission to the intensive care unit (ICU) or mortality on day three. Of 166 patients included in the study, 27 patients (29.7%) with TFAD <4 h had early clinical failure compared to 23 patients (37.7%) with TFAD >4 h (odds ratio [OR] 0.69; 95% confidence interval [CI] 0.35-1.35). In multivariate analysis, the pneumonia severity - index (OR 1.03; 95%CI 1.011.04), confusion (OR 2.63; 95%CI 1.146.06), Staphylococcus aureus infection (OR 7.26; 95%CI 1.3339.69) and multilobar pneumonia (OR 2.40; 95%CI 1.115.22) but not TFAD were independently associated with early clinical failure. Clinical parameters on admission other than the TFAD predict early clinical outcome in moderatesevere CAP. In contrast to severe CAP necessitating treatment in the ICU directly, in the case of suspected moderatesevere CAP, there is time to establish a reliable diagnosis of CAP before antibiotics are administered. Therefore, the implementation of the TFAD as a performance indicator is not desirable. Quality of care measurements and performance indicators are increasingly important in medical practice, in particular, in the treatment of high prevalence diseases [1]. Community-acquired pneumonia (CAP) is one of the leading causes of hospitalisation and mortality in the western world and is associated with high healthcare costs [2]. Therefore, performance indicators play an important role in the development of pneumonia care standards. Current guidelines advise to minimise the time to first antibiotic dose (TFAD) in patients suspected of pneumonia. Moreover, the TFAD has frequently been mentioned as an important performance indicator in patients admitted because of pneumonia [3]. The European guidelines recommendation is to initiate antibiotics within the first two hours of hospitalisation, whereas the current Infectious Disease Society of America/American Thoracic Society consensus guidelines advise the first antibiotic dose to be administered while the patient is still in the emergency department [4, 5]. These recommendations are mainly based on two retrospective database studies demonstrating an association between antibiotic timing and severityadjusted outcome in pneumonia [6, 7]. Therefore, as the advice to minimise the TFAD is only based on grade C level of evidence and more recent studies do not support their findings, the validity of these studies has been questioned [4, 812]. Additionally, minimising the TFAD is associated with drawbacks as well. Adopting the TFAD as a performance indicator may lead to the prioritisation of pneumonia patients over others and unnecessary antibiotic treatment for patients who ultimately receive another diagnosis (e.g. congestive heart failure), contributing to an increase in antibiotic use, side-effects, resistance and costs. Another concern is that patients may receive inappropriate antibiotics for suspected pneumonia due to time pressure [13, 14]. This is illustrated by a recent study which shows that linking TFAD within four hours (4 h) to financial compensation may result in less optimal care [15]. Preferably, performance indicators are based on recommendations with adequate scientific proof of their effectiveness, safety and efficiency [16]. The need for evidence is even more urgent in view of todays trend to use performance indicators as the basis for public reporting and plans to implement quality measures such as the TFAD in pay-for-performance programmes [17]. When adopting the TFAD as a quality measure in pay-for-performance programmes for the treatment of CAP, more studies on the impact of the TFAD on outcome are needed. Therefore, we prospectively studied the effect of the TFAD on early clinical outcome in patients hospitalised with moderate severe CAP admitted to general medical and pulmonary wards. Patients and setting The prospective cohort of patients in this study was derived from a multicentre prospective randomised controlled trial on the cost-effectiveness of an early switch from parenteral to oral therapy for severe CAP [18]. Patients were included during a three-year period from July 2000 to June 2003 in University Medical Centres and their affiliated teaching hospitals in the Netherlands. All adult patients (age 18 years and above) admitted to the hospital because of CAP were eligible for inclusion. CAP was defined as at least two symptoms of acute lower respiratory tract infection with onset before admission and a new or progressive pulmonary infiltrate on a chest radiograph. Written and oral informed consent was retrieved from all of the patients included. Moderatesevere pneumonia was defined as a pneumonia severity index score >90 and necessitating admission to the general medical or pulmonary ward, without immediate treatment in the intensive care unit (ICU) [19, 20]. Antibiotic treatment was based on the Dutch guidelines for pneumonia management [21]. Data collection and definitions For the current study, patients were included at the time of hospital admission and were followed for at least three days after diagnosis. On admission, data were collected on demographics, comorbidity, antibiotic use prior to admission, duration of symptoms before admission, pneumonia severity scores, the TFAD, site of administration of first antibiotic dose and initial choice of antibiotics [20, 22]. In addition, cultures, serology and urinary antigen tests were performed to establish an aetiological diagnosis. During follow-up, in-hospital clinical data were recorded. On the third day of admission, patients were evaluated for clinical outcome by means of clinical failure, including clinical instability, mortality and admission to the ICU. Clinical instability was defined as: respiratory rate >25/min, peripheral oxygen saturation <90%, partial pressure of arterial oxygen <60 mmHg, haemodynamic instability or altered mental status [23]. Indication for ICU admission was the n (...truncated)