J Med Microbiol. 2016 Dec;65(12):1512-1520. doi: 10.1099/jmm.0.000374.

Microbiological sentinel events at a neurological hospital: a retrospective cohort study.

Annalia Asti1, Elio Marmondi1, Carmine Tinelli2, Marta Corbella2, Annalisa De Silvestri2, Gaetano Bernardi1, Franco Andreini1, Anna Preti1 and Monica Bricchi1.

1 Fondazione IRCCS Istituto Neurologico ‘Carlo Besta’, Milano, Italy

2 Clinical Epidemiology and Biometric Unit, Fondazione IRCCS San Matteo, Pavia, Italy



The purpose of this study is to describe the epidemiological surveillance of microbiological sentinel events (SEs) carried out between 2012 and 2014 at the Neurological Hospital Carlo Besta, Milano, Italy. The setting is inpatient care with multidrug-resistant infections. The aim of the procedure is to formalize the management mode, reporting and transmission of SEs. Categorical variables were described by counts and percentages, as mean and SD or median and interquartile range. The incidence rates of SE were calculated per 1000 patient-days and for 100 admissions using Poisson distribution. The incidence rate of isolation for 1000 patient-days varies from a minimum of 0.52 (95 % confidence interval, 0.23  -1.15) for the second quarter of 2014 to a maximum value of 4.16 (95 % confidence interval, 3.20 – 5.40) for the first quarter of 2013. A decrease followed from the third quarter of 2013 that remained constant in 2014, reaching values similar to those of 2012. Preventive actions and their effectiveness on Acinetobacter baumannii, the primary cause in our division of multidrug-resistant infections in 2012, have ensured a reduction of the incidence of the same; preventive actions and their effectiveness allowed us to intercept microbiological SE and trigger appropriate precautionary behaviour and isolation. Surveillance of healthcare-associated infections is fundamental in understanding the sources that are contributing to the growing reservoir within hospital communities.



Sentinel Event indicate the presence of inadequate working conditions and the exposure to unacceptable risk factors such as the utilization of medical procedures, high-risk medical interventions and invasive devices, and failure of the hospital’s efforts to prevent infections that require an individual investigation [1,2] HAIs [3] that develop 48h after hospital admission of the patient [4] are dependent on two key pathophysiological factors: decreased host defences and colonization by pathogenic organisms; and infected or colonized patients who frequently serve as reservoirs of bacterial infection for other patients [5]. It has been demonstrated that each night spent in hospital increases, by 5%, the risk of acquiring hospital infections [6], and prolonged patient-days necessitate a number of medical procedures that increase the possibility of transferring hospital infectious pathogens [6,7].

The main goal of this study was to establish monitoring of SE in order to:

identify infection factors; . define the priorities and the most effective preventive measures; . take efficient action in the fight against HAI; . define the necessary precautions to be implemented; . avoid renewal of these precautions, and the evaluation of actions taken to reduce risk factors; assess the epidemiological occurrence of multi-resistant bacteria and attempt to identify preventive actions.

Based on the type and site of infection, clinical specimens such as pus/exudates, blood and indwelling medical device tubes and urinary catheters were collected from the patients and processed by the microbiology laboratory. Data were obtained from microbiological isolation in culture tests from hospitalized patients, collected during routine visits. Microbial sampling, in terms of periodicity, was carried out for the intensive care unit, where surveillance of SE was performed twice a week every week for up to three successive negative outcomes, and for all other units was performed once a week.

Study design. The procedure is aimed at formalizing the management mode and the reporting and transmission of SE. A cohort study with retrospective data (i.e. in which data on SE and determinants, including interventions decided independently of this study, were collected at the end of study period for previous years) was performed to examine the incidence of SE from 1 January 2012 to 31 December 2014. The incidence rates (IRs) of SE were calculated per 1000 patient-days for 100 admissions [with relevant 95% confidence intervals (CIs) using Poisson distribution. The Poisson regression model was used to analyze both the temporal trend and associations among age, sex, patient-day and hospitalization within 30 days of the previous analysis. The results are expressed as IR ratio (IRR) with 95% Cis.

Data show that between the end of 2012 and the first quarter of 2013, there was a significant increase in all departments surveyed. For medical/neurological units, there was an increase in the isolation rate of 1.9 per 1000 patient days. This peak was followed by a decrease in the rate in medical units (from 3.1 to 1.1) (P=0.04) and intensive care units (from 8.7 to 5.9).

Trend analysis related to SE for the period 2012 – 2013 shows an increase in isolated E. coli and K. pneumoniae resistant to cephalosporins, and in micro-organisms like Staphylococcus aureus, albeit with rates per 1000 hospitalizations lower than the regional average for the same period (see Fig. 1 ).


Fig. 1 Sentinel Events in 2012/2013 at Neurological Hospital. Rate for 1000 LOS


In general, there has been a reduction of the number of the species isolated (10, 24 and 12 species in 2014, 2013 and 2012, respectively), in particular, some Enterobacteriaceae identified in 2012 and 2013 were not isolated, and the isolation rate of methicillin-resistant S. aureus (MRSA) was also lower (Fig. 2). In surgical patients undergoing treatment with invasive surgical devices, proper use of preoperative antibiotic prophylaxis obviates the extension of antibiotic therapy and the implementation of measures required to contain the infection.

The strict control carried out and the implementation of measures to prevent or contain Acinetobacter baumannii, which was the primary cause found in our department of HAI MDR in 2012, have ensured a reduction in the incidence of the same; however, this species remained one of the main micro-organisms involved in the department in 2013. Concern over resistance to β-lactam agents among nosocomial Gram-negative pathogens has increased recently because of the widespread availability and use of these drugs, particularly cephalosporins [8]. The availability of other extended-spectrum β-lactam agents has shifted attention from the aminoglycosides towards a different set of resistance mechanisms for these Gram-negative bacilli.



Fig.2 Number of Species isolated in 2014 and Sentinel Events
Legend: SE= Sentinel Events, Sp.n= Specimen number, Pts= Patients



The main goals that we achieved are the decreased incidence of HAI in a particularly badly affected unit, such as neurosurgery; for the most part, these patients underwent central venous and urinary catheterization with compromised general and neurological conditions, and in these cases antibiotic pressure was high. The goal we achieved in 2014 was that over 80 % of SE were found to be from colonization and contamination; only when cultural examinations for SE were shown to be negative did the transfer of patients to other facilities proceed (Table 1).

In summary, the updated results of our study indicate that in the regard to the decreased incidence of MDR micro-organisms, accurate epidemiological information is needed to formulate appropriate empirical therapy , together with the fact that the microbiology laboratory plays a crucial role in clinical diagnostics. The consequence has been several treatment failures in patients who received inappropriate antibiotics and suffered from MDR; indeed, the use of antimicrobial agents tends to create selective pressure that promotes the emergence of resistant organisms [9,10]; when inappropriate antibiotic therapy is given, mortality rates doubled [11]. Consolidation of an of antibiotics policy, characterized by antibiotic selection and the implementation of de-escalation [12] is a topic of this paper. The purpose of the study was to identify causes, transmission paths and contributory factors such as antimicrobial resistance, protocols and foreign material, in order to formulate a prevention strategy.



Table 1. Rate for 1000 LOS at Neurological Institut in 2014



Acknowleges: authors wish to thank Dott. Angelo Cordone of Istituto Besta, Milano and Prof. Gaetano Filice of Infectious Disease Department, Pavia.



1 Emori, T. G. & Gaynes, R. P. (1993). An overview of nosocomial infections, including the role of the microbiology laboratory. Clin Microbiol Rev 6, 428–442
2 Kluytmans–VandenBergh, M. F. Q., Kluytmans, J. A. J. W. & Voss, A. (2005). Dutch guideline for preventing nosocomial transmission of highly resistant microorganisms (HRMO). Infection 33, 309–313.
3 Vincent, J. L. (2003). Nosocomial infections in adult intensive-care units. Lancet 361, 2068–2077
4 Custovic, A., Smajlovic, J., Hadzic, S., Ahmetagic, S., Tihic, N. & Hadzagic, H. (2014). Epidemiological surveillance of bacterial nosocomial infections in the surgical intensive care unit. Mater Sociomed 26, 7–11.
5 Jarvis, W. R. (1996). The epidemiology of colonization. Infect Control Hosp Epidemiol 17, 47–52.
6 Hauck, K. & Zhao, X. (2011). How dangerous is a day in hospital? A model of adverse events and length of stay for medical inpatients. Med Care 49, 1068–1075
7 World Health Organization (2002). Prevention of Hospital-Acquired Infections. a Practical Guide, 2nd edn. Geneva: WHO/CDS/CSR/EPH.
8 Gaibani, P., Ambretti, S., Berlingeri, A., Gelsomino, F., Bielli, A., Landini, M. P. & Sambri, V. (2011). Rapid increase of carbapenemase-producing Klebsiella pneumoniae strains in a large Italian hospital: surveillance period 1 March-30 September 2010. Euro Surveill 16, 19800
9 Barlow, G. & Nathwani, D. (2005). Is antibiotic resistance a problem? A practical guide for hospital clinicians. Postgrad Med J 81, 680–692.
10 Chen, L. F., Freeman, J. T., Nicholson, B., Keiger, A., Lancaster, S., Joyce, M., Woods, C. W., Cook, E., Adcock, L. & other authors (2014). Widespread dissemination of Ctx-M-15 genotype extended-spectrum-blactamase-producing Enterobacteriaceae among patients presenting to community hospitals in the southeastern United States. Antimicrob Agents Chemother 58, 1200–1202
11Wisplinghoff et al., 2004). Wisplinghoff, H., Bischoff, T., Tallent, S. M., Seifert, H., Wenzel, R. P. & Edmond, M. B. (2004). Nosocomial bloodstream infections in US
12 Christoff, J., Tolentino, J., Mawdsley, E., Matushek, S., Pitrak, D. & Weber, S. G. (2010). Optimizing empirical antimicrobial therapy for infection due to Gram-negative pathogens in the intensive care unit: utility of a combination antibiogram. Infect Control Hosp Epidemiol 31, 256–261