Weekly screening supports terminating nosocomial transmissions of vancomycin-resistant enterococci on an oncologic ward – a retrospective analysis

Vancomycin-resistant enterococci (VRE) are important causes of healthcare associated infections [1, 2]. Acquisition of VRE has been associated with prolonged hospital stay and duration of previous hospitalization, neutropenia, antibiotic treatment, exposure to high-dose corticosteroids and immunosuppression [3‐6]. Patients with hematologic malignancies have many of these predisposing factors and are at high-risk for VRE colonisation and infection.

Recent studies report an increase in VRE outbreaks on wards, hosting immunocompromised patients [7‐9]. Mathematical modelling estimated a basic reproductive number R₀ of 1.32, underlining the epidemic potential of VRE [10]. Via shedding VRE, colonised patients serve as potential sources for transmission on other patients, healthcare workers or surfaces [4]. Limiting the spread of VRE requires infection control bundle strategies such as antibiotic stewardship, patient isolation, enhanced hand hygiene, surface disinfection, and increased active surveillance [11, 12].

Screening to detect VRE carriage in risk patients is usually used to identify previously unrecognized cases on a ward in order to prevent further nosocomial spread and subsequent infections of VRE. Distinguishing community-acquired VRE cases from cases transmitted in the hospital is often difficult. Appropriate screening strategies can help to differentiate among these cases and to detect clusters of VRE. International recommendations prefer active rather than passive screening methods in hospitals [13] but due to imprecise definitions, currently performed screening strategies diverge, depending on the respective hospital. In current studies, VRE screening is mainly considered within the context of preventive activities [14]. Here, we investigate the impact of weekly VRE screening within the bundle of infection control measures to terminate VRE outbreaks on an oncologic ward.

Between January and April 2015 five VRE isolates from clinically relevant specimens (two blood cultures, three urines) were detected in patients on the haematology/oncology ward. Point prevalence determination of patients on the ward revealed 12 of 29 patients positive for VRE, of which 10 were per definition hospital-acquired, since admission screening was not performed or negative. After establishing the VRE bundle strategy, on average 7 of 40 (17.5%) patients were detected to be VRE colonised in in admission screenings, showing no significant decline compared to the initial situation. In total 30% of investigated outbreak strains harboured vanA, 68.3% vanB and 1.6% both resistance genes. MLST ST 192 (41.7%) and ST 203 (18.3%) were most prevalent (Table 1). cgMLST revealed five different VRE clusters in parallel comprising patients and environmental isolates; of these clusters three exhibited a vanB and two a vanA resistance genotype (Fig. 1).

To evaluate effectiveness of weekly screening in addition to the VRE bundle strategy, percentages of screened, colonised, hospital-acquired and isolated patients were analysed: After implementation of admission screening in May 2015 the percentage of screened patients was 76%. With establishing weekly screening in the end of August 2015 on average 91% of all patients on ward were screened (see also Fig. 2). The number of colonised patients in January 2016 declined to 1 of 53 (~2%, p = 0.00001) and no further nosocomial cases were detected (p = 0.00001) (Fig. 3). Closely connected to this situation, the number of weekly isolated patients due to a positive VRE status declined significantly from 21 of 55 patients in May 2015 to 6 of 59 patients in January 2016 (p = 0.00007) (Fig. 3a). While the number of community-acquired VRE did not change remarkably comparing May 2015 to January 2016, the number of total VRE colonisations decreased significantly due to a decline in hospital-acquired VRE colonisations (Fig. 3).

Within the here presented study, spread of VRE on the oncologic ward was suspected, in particular after the initial point prevalence of VRE colonisations was determined 41.3%. During the following months (May–August) VRE colonisation rate on admission was 17.5%, which clearly exceeds admission prevalence published elsewhere [12]. This might be due to the fact, that a high number of patients, including VRE colonised patients, was repeatedly admitted in two- or three-week- intervals for chemotherapeutic treatment. Data of detected MLST ST and van-genotypes, both comparable to published investigations on clinical E. faecium isolates [17], provided a first hint, that different VRE clones were circulating on this ward. Of note, we found MLST ST 192 and ST 203, which are the most causative STs of German VRE outbreaks [17‐19], to be most prevalent on this ward. Interestingly, MLST ST 117 or ST 80, as e.g. found during VRE outbreaks in German neighbouring countries (Denmark, the Netherlands) [16], did not play a major role in our setting. cgMLST, which can be used to precisely monitor transmission rates [15], helped to illustrate, that spread of different VRE clones had taken place.. This spread was ended after establishment of weekly screening in addition to common infection control bundle strategies. Published studies mostly evaluate screening within non-outbreak settings. Here, active screening on high-risk wards was shown to reduce the incidence of VRE bacteraemia and colonisations compared to wards also hosting high-risk patients but not performing active screening [20]. The results of the present study indicate that even in situations of VRE spread, weekly screening supports reduction of VRE colonisations and infections. The combination of VRE bundle strategies plus weekly screening turned out to be most effective. These findings surprise, as weekly screening per se does not reduce transmission rates [21]. Screening approaches alone can help uncover undetected VRE colonisations and identify potential patient reservoirs early in order to prevent transmission of VRE within a bundle of infection control strategies, while the application of infection control measures as hand hygiene and contact precautions has more significant effect on terminating VRE transmissions [13, 22]. A possible explanation why weekly screening has a direct influence in terminating spread of VRE might be that personnel’s awareness is increased, if patients are weekly monitored and detected. In addition, since VRE cannot only be transmitted via direct or indirect contact but can also be selected due to the use of antibiotic agents, weekly screening serves the possibility of a colonisation follow up. Standard and extended hygienic measures can than concentrated and expanded when appropriate and VRE colonisation dynamics among patients on ward is more apparent.

Our study has limitations. First, we did not perform a case-control study. Hence, other interventions on the ward could have been responsible for decreased VRE colonisations. However, since all other measures of our VRE bundle were already implemented when transmission began and were not changed during the intervention period, this fact has a presumably small influence on the presented results. Second, we used different methods for susceptibility testing of either clinical or environmental samples. Routinely clinical samples are tested via VITEK 2 in order to have other therapeutic possibilities for patient’s treatment. In contrast, environmental samples, that are collected to clarify the distribution of VRE on surfaces, are tested for vancomycin resistance via Etest® since no therapeutic interventions are derived from these findings. Nevertheless, susceptibility evaluation was done in accordance with the latest EUCAST criteria, thereby creating comparable results. Third, we investigated the clonal spread of VRE only using cgMLST, therefore, we could not exclude whether vanA or vanB were passed via horizontal gene transfer from one strain to another as investigated elsewhere [18, 23].

Our study support the hypothesis, that active screening reduces the incidence of VRE infections and colonisations in high-risk patients by the early uncovering of nosocomial transmissions prior their appearance in clinical samples. Therefore, a weekly screening should be considered as part of a bundle strategy for the successful termination of VRE outbreak situations.