Infections caused by KPC-producingKlebsiella pneumoniae: differences in therapy and mortality in a multicentre study—authors' response

Sir, Tascini et al.1 offered some comments on our article2 entitled ‘Infections caused by KPC-producing Klebsiella pneumoniae: differences in therapy and mortality in a multicentre study’. Their points mainly concerned the susceptibility test utilized in our study and the use of carbapenems. We are aware that commercial automated systems for antimicrobial susceptibility testing such as Vitek 2 (bioMérieux, Marcy-l'Étoile, France) might not be completely accurate when testing some antibiotic/organism combinations, such as tigecycline and gentamicin against carbapenem-resistant Enterobacteriaceae.3–5 On the other hand, similar problems of low accuracy have been reported with Etest (bioMérieux), and recently Arena et al.3 demonstrated that the overestimation of gentamicin MICs by Etest translated into a categorical agreement rate of 52.6% compared with the reference broth microdilution (BMD) method. Moreover, Hindler and Humphries6 reported that when colistin MICs were estimated using the Etest method, discrepancies occurred in around 30% of K. pneumoniae isolates. For this reason, many Italian microbiology laboratories use both methods (i.e. Vitek and BMD) for testing certain problematic antibiotic/organism combinations. In our study the Vitek 2 system was routinely used in all participating hospitals, but in >80% of cases in vitro susceptibility was re-assessed with the Sensititre BMD method (Trek Diagnostic Systems, Cleveland, OH, USA). Thus, the hypothesis that an overestimation of resistance to gentamicin with the Vitek 2 system might have altered the data on monotherapy seems unlikely. In addition, none of the 307 patients in the monotherapy group was treated with more than one antibiotic (colistin, gentamicin or tigecycline) in definitive regimens. Coming to the issue of carbapenem use, we are of course aware that many hospital stewardship programmes, aimed at reducing the development of resistance, call for a limitation in the use of carbapenems. However, this is easier to say than to do, given the paucity of antibiotics active against MDR Gram-negative bacteria. On the other hand, the use of carbapenems for the targeted treatment of severe KPC-producing K. pneumoniae infections is certainly not the only reason for the diffusion of carbapenem-resistant isolates. The indiscriminate use of carbapenems in empirical therapies is the true problem, and antimicrobial stewardship programmes should aim at reducing carbapenem overuse, by avoiding unnecessary empirical therapies, reducing treatment duration and favouring de-escalation programmes. In addition, managing MDR infections requires an open mind and the reduction of any hypothetical overuse of an antibiotic class is just one of the many actions that should be implemented. Concerning the last issue (i.e. polymicrobial infections), as shown in Figure 1, patients with polymicrobial infections were excluded from the analysis. In conclusion, we agree that although published data2,7 indicate a possible role of carbapenems in the management of infections caused by carbapenemase-producing Klebsiella species, the true effectiveness of such an antibiotic strategy (particularly for isolates with high MICs of meropenem) should be further evaluated in prospective randomized clinical trials. None to declare.