Antibiotic stewardship programmes in intensive care units: Why, how, and where are they leading us

Table 2 Protocol-based antibiotic stewardship programmes

Ref.	Year	Pubmed ID	Study type	Outcome	No. of patients	Type of ASP	Major findings	Limitations/Confounding factors
Singh et al[54]	2000	10934078	RCT Follow-up N/A	1 LOS 2 Mortality 3 Proportion of patients with resolution of pulmonary infiltrate	81	Clinical Pulmonary Infection Score-based De-escalation	1 Positive study 2 ↓ in total antibiotic days from 9.8 to 3 d 3 ↓ of antibiotics cost by $381 per patient 4 ↓ in LOS from 14.7 to 9.4 d mean 5 Significant ↓ in total antibiotic resistance 6 No change to mortality	1 79% surgical patients 2 Mean APACHEII score of 42.7 in intervention group 3 Unknown follow-up period
Nobre et al[47]	2008	18096708	Single-centred RCT	1 Antiiotic Antibiotic use 2 28-d mortality 3 LOS 4 Incidence of clinical cure 5 Recurrence of infection 6 Incidence of nosocomial superinfection	79	PCT-based De-escalation	1 Positive study 2 ↓ in duration of treatment from median 9.5 to 6 d 3 ↓ in ICU LOS from 5 to 3 d 4 ↓ in hospital LOS 21 to 14 d 5 No change to mortality	1 Small study 2 Sepsis patients only 6 Infections by Pseudomonas, Acinetobacter etc. were excluded 7 Patients with chronic infections were excluded 8 Immunocompromised patients were excluded 9 Patients on antibiotics at time of admission were excluded
Hochreiter et al[48]	2009	19493352	Single-centred RCT	1 Antibiotic use 2 LOS 3 Mortality	110	PCT-based De-escalation	1 Positive study 2 ↓ in duration of treatment from median 7.9 to 5.9 d 3 ↓ in LOS from median 17.7 to 15.5 d 4 No change to mortality	1 Patients on antibiotics at time of admission were excluded 2 Sepsis patients only
Schroeder et al[49]	2009	19034493	Single-centred RCT	1 Antibiotic use 2 LOS 3 Mortality	27	PCT-based De-escalation	1 Positive study 2 ↓ in duration of treatment from 8.3 to 6.6 d 3 ↓ in antibiotic cost by 17.8% 4 No change to LOS 5 No change to mortality	1 Sepsis patients only
Stolz et al[55]	2009	19797133	Multi-centred RCT	1 No. of days without antibiotics at 28 d 2 Number of days without mechanical ventilation 3 ICU mortality 4 LOS 5 Incidence of VAP	101	PCT-based De-escalation	1 Positive study 2 27% ↓ in duration of treatment 3 No change to mortality 4 No change to LOS	1 VAP patients only
Bouadma et al[50]	2010	20097417	Multi-centred RCT (PRORATA trial)	1 28-d and 60-d mortality 2 Number of days without antibiotics at 28 d 3 Incidence of recurrence of infection or superinfection 4 Days of unassisted breathing 5 LOS 6 Antibiotic use 7 Incidence of MDR organisms	630	PCT-based Escalation/De-escalation	1 Positive study 2 ↓ in duration of treatment from 13.3 to 10.3 d 3 No change to mortality 4 No change to LOS	1 Patients on antibiotics on admission were excluded 2 Patients with chronic infection were excluded 3 Immunocompromised patients were excluded 4 90% medical patients 5 Close to 50% respiratory/CVS failure, and > 30% CNS failure 6 70% pulmonary infection site 7 53% did not adhere to algorithm in PCT group
Jensen et al[51]	2011	21572328	Multi-centred RCT (PASS trial)	1 28-d mortality	1200	PCT-based Treatment escalation	1 Negative study 2 Significant ↑ in duration of tretment (Median: from 4 to 6 d), especially for tazocin and meropenem 3 ↑ in LOS from median 5 to 6 d 4 No change to mortality	1 Low resistance and antibiotic usage units 2 Incomplete adherence to PCT algorithm
Layios et al[52]	2012	22809906	Single-centred RCT	1 Antibiotic use 2 Accuracy of infectious diagnosis 3 Diagnostic concordance between intensive care unit physician and ID specialist	510	VAP -based Escalation	1 Negative study 2 No change in duration of antibiotic treatment 3 No change in DDD 4 No change to LOS 5 No change in mortality	1 41% surgery and trauma patients
Annane et al[53]	2013	23418298	Multi-centred RCT	1 Proportion of patients on antibiotics at day 5	62	PCT-based Escalation	1 Negative study 2 Premature termination	1 Poor clinician compliance with algorithm 2 Patients on antibiotics at time of admission were excluded

LOS: Length of stay; VAP: Ventilator-associated pneumonia; ICU: Intensive care units; ASP: Antibiotic stewardship programme; DDD: Defined daily dose; RCT: Randomised Controlled Trial; APACHEII: Acute Physiology and Chronic Health Evaluation II; PCT: Procalcitonin; CVS: Cardiovascular system; CNS: Central Nervous system; XDR: Extensively Drug-Resistant.