The results of our work show that, in an endemic situation, the administration of antimicrobials, as well as the antibiotic pressure of cephalosporins and carbapenems, is related to increased colonisation by MR K. pneumoniae strains.
The expansion of MR bacteria is now one of the main concerns for critical patient units. Different authors have analysed the effect of antimicrobial consumption on colonisation by MR strains in these units, and have found a clear association between the individual consumption of antipseudomonal drugs and colonisation or infection by MR P. aeruginosa [17, 18] or A. baumannii strains [9, 19]. However, even though this species is expanding, the effect of administering antimicrobials on the rate of K. pneumoniae colonisation in these units has been little studied [20, 21]. Unlike previous studies [18,19,20], we included both rectal and respiratory samples which increased the probability of identifying patients colonised by these strains.
The results we obtained show that the length of stay in the ICU is a factor that determines colonisation by MR strains of K. pneumoniae, whose colonisation prevalence exceeded 50% in patients who remained in the unit for more than three weeks. However, we have also demonstrated that patients who received antibiotic treatments were colonised earlier, showing that, although the unit hospitalisation length inevitably conditions the risk of colonisation, the consumption of antibiotics is a key factor in accelerating it. Changes in the microbiota observed in critically ill patients [22, 23] could be favored by the use of antibiotics, which would bring on the selection and persistence of the most resistant strains. It should be noted that certain patients remain without being colonized despite having been admitted to the unit for several weeks and despite having received different antibiotic treatments.. It has been postulated that there could be factors specific to the flora of the host, which are currently not understood, that might act as protectors against exogenous strains .
Among the antimicrobials studied, use of the penicillin/BLI and aminoglycosides combination has been associated with a significant colonisation risk. The capacity of penicillins/BLIs to select MR strains is well known [25, 26]. However, data referring to the use of aminoglycosides are more controversial and disparate results have so far been reported in the literature [17, 18, 25]. Carbapenems did not appear to have any significant effect on individual patient exposure or colonisation by MR strains. This phenomenon could be explained in part because in our unit, this antibiotic is usually used in patients who are already colonised by MR strains, and who completed their follow-up in our study.
With respect to the pressure on antimicrobial consumption, very few studies have evaluated the overall effect of the use of antibiotics and colonisation by MR strains in ICU units . In the present study, we found an association between the global consumption of carbapenems and cephalosporins, and colonisation in the month following the intervention. The effect produced by this group of antibiotics and their capacity to select for MR bacteria is known, having been related to a selective pressure on the microbiota [10, 26]. However, it should be noted that no association was found between the overall consumption of quinolones or BLIs and the number of colonised patients, even though these are also frequently cited in the literature as factors related to the selection of MR strains [9, 18, 27], and despite the fact we found an individual effect in the case of BLI. This current analysis shows that, although the consumption of antibiotics seems to lead to higher overall colonisation, analysis of the association between the antimicrobial-use pressure and the development of resistance is complex. It should be pointed out that the evaluation of the impact of antibiotics on in critically ill patients microbiota is highly complex because of the heterogeneity of dosing regimens, the co-administration of other antibiotics and other drugs that may also impact on its diversity. Therefore, to reduce the colonisation pressure, in addition to minimising exposure to antibiotics, it is essential to apply measures that have been shown to reduce colonisation from other patients or from colonised environmental surfaces; these measures include handwashing surveillance programs, adequate cleaning of patients, and the use of diverse strategies to minimise surface contamination [28, 29].
Among the limitations of the study is, first of all, its unicentric nature. The analysed data come from a medical unit with specific epidemiological characteristics, which may not be applicable to other units with other types of MR strains. This study has been focused on MR K. pneumoniae. Most of patients that have other MR bacteria, such MRSA, E. cloacae, P. aeruginosa o A. baumannii had been admitted to other units prior to their entry into the ICU, with a high suspicion that they could have been colonized in them. However, K. pneumoniae is an endemic bacteria of the ICU within our hospital, so we could study the effect of antibiotic use on the incidence of K pneumoniae colonisation better than with the set of MR strains, with a lesser influence of external factors to those of the ICU.
We have presented an ICU we a high proportion of carbapenem-produced K. pneumoniae colonisation with a relatively low consumption of carbapenems, which reflects the endemic situation of the unit. It should be noted that, in an endemic situation, most patients are colonised through cross-transmission via several different materials and from the health professionals themselves . This is why most patients may be initially colonised on a surface of their body before later presenting colonisation of their digestive tract, from where the surveillance samples are obtained. The effect of antibiotic consumption on this type of transmission is uncertain. However, the loss of the bacterial flora because of the use of antimicrobials could facilitate this colonisation phenomenon.
Although surgical intervention has been associated with higher colonisation by MR bacteria , we did not include this variable as a colonisation risk factor in our study because our ICU does not see surgical patients. Similarly, we did not study the impact of the insertion of central venous catheters on colonisation, even though other authors have demonstrated that this is a risk factor for infection by MR strains [12, 25], because most of the patients admitted to our unit have this type of line. On the other hand, some patients were evaluated during their stay in our unit but not subsequently followed-up in the hospitalisation rooms. This means that the true number of colonised patients may have been underestimated. In addition, during this period, even though our ICU had agreed-upon protocols that were well-known by the unit’s staff, we were unable to rigorously analyse compliance with the various strategies in place to help prevent patient colonisation. This fact, together with the issue that the different measures were carried out at different times during the follow-up period, has prevented the effect of these interventions from being included in the analysis.