Patterns of antimicrobial therapy in severe nosocomial infections: empiric choices, proportion of appropriate therapy, and adaptation rates—a multicentre, observational survey in critically ill patients (original) (raw)

2010, International Journal of Antimicrobial Agents

This prospective, observational multicenter (n=24) study investigated relationships between antimicrobial choices and rates of empiric appropriate or adequate therapy, and subsequent adaptation of therapy in 171 ICU patients with severe nosocomial 36 infections. Appropriate antibiotic therapy was defined as in-vitro susceptibility of the 37 causative pathogen and clinical response to the agent administered. In non-38 microbiologically documented infections, therapy was considered adequate in case of 39 favorable clinical response <5 days. Patients had pneumonia (n=127; 66 ventilator-40 associated), intra-abdominal infection (n=23), and bloodstream infection (n=21). 41 Predominant pathogens were Pseudomonas aeruginosa (n=29) Escherichia coli (n=26), 42 Staphylococcus aureus (n=22), and Enterobacter aerogenes (n=21). In 49.6% of infections 43 multidrug resistant (MDR) bacteria were involved, mostly extended-spectrum Beta-44 lactamase producing Enterobacteriaceae and MDR non-fermenting Gram-negative 45 bacteria. Prior antibiotic exposure and hospitalization in a general ward prior to ICU 46 admission were risk factors for MDR. Empiric therapy was appropriate/adequate in 47 63.7% of cases. Empiric schemes were classified according to coverage of (i) ESBL-48 Enterobacteriaceae + non-fermenting Gram-negative bacteria (meropenem-based), (ii) 49 non-fermenting Gram-negative bacteria (schemes with antipseudomonal agent), and 50 (iii) first-line agents not covering ESBL-Enterobacteriaceae nor non-fermenting Gram-51 negative bacteria. Meropenem-based schemes allowed for significantly higher rates 52 of appropriate/adequate therapy (p<0.001). This benefit remained when only 53 patients without risk factors for MDR were considered (p=0.021). In 106 patients 54 (61%) empiric therapy was adapted: in 60 cases following initial 55 peer-00567278, version 1 -A c c e p t e d M a n u s c r i p t 3 inappropriate/inadequate therapy, in 46 patients in order to fine-tune empiric 56 therapy. In this study reflecting real-life practice first-line use of meropenem 57 provided significantly higher rates of appropriate/adequate therapy, irrespective of 58 presence of risk factors for MDR. 59 60 A c c e p t e d M a n u s c r i p t 65 on the presence of particular iatrogenic risk factors such as the use of indwelling 66 devices and extensive surgery, as well as the severity of underlying disease and 67 critical illness. Despite several large scaled efforts to improve prevention of 68 healthcare-associated infection [2-7], in general about 20% to 50% of patients 69 hospitalized in intensive care units (ICUs) experience infection, either hospital or 70 ICU-acquired [8, 9]. 71 Severe nosocomial infection carries a substantial economic burden due to extensive 72 antimicrobial consumption and, even more importantly, increased length of 73 hospitalization [10-13]. In addition, severe infection seriously compromises the odds 74 of survival. Attributable mortality rates vary from as low as zero percent to a 75 dramatic 50% dependent of the type of infection, the causative pathogen, patient age, 76 associated co-morbidities, and overall quality of the anti-infective approach [13-21]. 77 Among all the modalities that are to be fulfilled in the aim to optimize clinical patient 78 outcomes, early initiation of the proper antimicrobial agent is a cornerstone [1]. 79 Failure to timely administer appropriate antimicrobial therapy results in a dramatic 80 increase in fatality rates [22-25]. Selecting an empiric regimen which covers the 81 causative pathogen, however, is hampered by the presence of multidrug resistant 82 (MDR) micro-organisms which is the utmost important cause of empiric 83 inappropriate therapy. Since antimicrobial consumption in itself is a major trigger for 84 peer-00567278, version 1 -A c c e p t e d M a n u s c r i p t 5 MDR development, physicians are frequently urged to thoughtfully use 'last-line 85 antibiotics'. In fact, the challenge is to achieve high rates of empiric appropriate 86 therapy in order to optimize patient survival, while avoiding unnecessary use of 87 antibiotics with the intention to minimize microbial selection pressure, and hence, 88 MDR development [1, 26]. 89 In order to accomplish this goal, in the past decade two main strategies have been 90 proposed. In the surveillance-assisted strategy, the empiric regimen is selected 91 mainly based on the presence or absence of MDR pathogens in routine surveillance 92 cultures. The strength of this approach is the high negative predictive value of 93 surveillance cultures to predict MDR involvement in subsequent infection. On the 94 condition that cultures are taken at least twice weekly, this strategy is capable to 95 combine high rates of empiric appropriate therapy with reduced consumption of 96 antibiotics in pneumonia and bacteremia [27-33]. The cost-effectiveness of this 97 approach, however, remains questionable. Another approach is the so-called 'de-98 escalation strategy' which, on the condition of risk factors for MDR involvement, 99 recommends empiric start with a regimen which covers most potential MDR 100 pathogens such as extended-spectrum beta-lactamase producing (ESBL) 101 Enterobacteriaceae, non-fermenting Gram-negative bacteria, and methicillin-resistant 102 Staphylococcus aureus (MRSA) [34-36]. Once culture results are available, and if 103 feasible, narrowing the antimicrobial spectrum is advised. This concept, often 104 referred to as 'de-escalation', is widely used and advocated [37-40]. This strategy has 105 been demonstrated to be successful and safe, and may also reduce antibiotic use and 106 hence limiting the emergence of MDR [36, 41]. The objective of the present study was to prospectively investigate patterns of 108 antimicrobial therapy in critically ill patients with nosocomial infection. More 109 precisely we formulated the following research questions: (i) What is the rate of 110 empiric appropriate or adequate therapy achieved? (ii) Which antibiotic selections 111 allow for the highest rates of empiric appropriate or adequate therapy, either in the 112 presence or absence of risk factors for MDR pathogens? (iii) What is the rate by 113 which empiric therapy (either appropriate/adequate or not) is adapted? 114 115 116 study was approved by the local ethics committee and informed consent was 120 requested. In all centers antimicrobial prescribing was done or supervised by the 121 attending senior intensivist. 122 Inclusion criteria. Eligible patients were those who provided informed consent, were 123 at least 18 year of age, were hospitalized in the ICU, and experienced severe hospital-124 acquired infection, either pneumonia, intra-abdominal infection, primary 125 bloodstream infection, or secondary bloodstream infection originating from another 126 source than pneumonia or intra-abdominal infection (e.g. bacteremia secondary to 127 urinary tract infection or sinusitis).