When patients are transferred between hospitals, information regarding MDRGNB colonization or infection must also be transferred to ensure continuous implementation of infection control measures. This is usually supported by indicating on antibiograms, which are included in the records of a transferred patient, whether the respective bacteria are multidrug-resistant according to the national guideline. For cross-border healthcare, this implies that clinicians or infection control staff can interpret antibiograms according to guidelines from both countries or understand foreign ‘MDRGNB languages’. The aim of this study was to describe different classifications used in The Netherlands and Germany in order to estimate the risk, which might be caused when patients infected or colonized with MDRGNB are transferred across the border without recognizing the respective bacteria as multidrug-resistant.
When planning the data analysis, a first hurdle occurred when the authors tried to actually understand the respective classification guidelines in detail. We learned that parts of the practical applicability of the guidelines (from both sides of the border) are rather locally defined. For example, in the Dutch guideline, it is not explicitly mentioned for Enterobacteriaceae, which fluoroquinolones (e.g., ciprofloxacin, levofloxacin, norfloxacin, moxifloxacin) and aminoglycosides (e.g., gentamicin, tobramycin, amikacin) should be considered for the classification of which bacterial species and how to categorize, if one quinolone is resistant and the other susceptible. In the German guideline, some exceptional rules, such as ignoring imipenem non-susceptibility in Serratia or Proteus for the classification (due to unreliable test results) are not mentioned, and can only be concluded from other guidance papers or publications of German reference laboratories. This might cause problems if microbiological laboratories are working across the border and might be perceived as a lack of transparency. This issue could be improved when national policy makers published more detailed standard operating procedures for laboratories where the problems occurring in daily routine are more accurately described.
Overall, the Dutch guideline makes it more laborious for a microbiological laboratory to actually classify an isolate as MDRGNB (tests for phenotypic ESBL-production and VIM-carbapenemase encoding genes). This might reflect structural differences in the organization of microbiological diagnostics between the two countries, as more laborious confirmation testing requires using more financial resources.
The bulk of isolates, which were classified differently, were E. coli
isolates characterized by ESBL-production, but being susceptible to fluoroquinolones. In German hospitals, no other than basic hygiene measures are taken for patients colonized or infected with these strains. This can be criticized, because spread of ESBL-producers might increase carbapenem use. Moreover, ESBLs are usually encoded on plasmids, which can be transferred independently from the bacterial clone even to other bacterial species. However, recent investigations have shown, that clonal spread of ESBL-E. coli
in healthcare settings is rarely observed [8
]. A second reason for divergent classifications was that the Dutch guideline uses combined fluoroquinolone and aminoglycoside resistance as a criterion for multidrug resistance. Aminoglycosides are not considered in the German guideline, maybe due to their limited and decreasing use in German hospitals compared with The Netherlands (<0.5 vs. 3.7 daily defined doses (DDD)/100 patient-days) [10
]. Thirdly, major differences were also found for P. aeruginosa
. Many of the very broadly resistant P. aeruginosa
isolates, for which colistin, tobramycin, or new β-lactams (such as ceftolozane/tazobactam) were the only remaining treatment options, were not classified as MDRGNB by the Dutch guideline, because VIM-carbapenemases were not detected. In this context, we clearly overestimated the disagreement between the Dutch and German guideline (Table 4
), because we considered all 1,107 carbapenem-resistant P. aeruginosa
isolates (of 5058 not classified as BRMO) as VIM-negative. This is not probable as it is well known that in Germany up to 24% of carbapenem-resistant P. aeruginosa
isolates harbor carbapenemases among which VIM is predominant [12
]. This points towards a major limitation of this study. Since the analysis was not prospectively planned, we had to cope with missing data. Of course, excluding 3832 antibiograms (which is >10% of the antibiograms collected in the participating hospitals) due to a lack of information about phenotypic ESBL-test results for non-E. coli
isolates might have caused significant impact on the results. However, the total numbers Enterobacter
, or Hafnia
isolates included from both sides of the border was comparable. Overall, the results of this study demonstrate that in contrast to other multidrug-resistant bacteria such as methicillin-resistant Staphylococcus aureus
or vancomycin-resistant enterococci, those resistance pheno- or genotypes that define Gram-negative bacteria as MDRGNB markedly differ between The Netherlands and Germany. For cross-border care, the easiest solution would be to harmonize the classification rules of both countries. As long as this is not done, the full antibiogram data of Gram-negative bacteria should be transferred together with the patient in order to enable classification by local infection control staff.