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Emergence of Infections due to a Polymyxin B–Resistant KPC-2-Producing Klebsiella pneumoniae in Critically Ill Patients: What Is the Role of a Previous Colonization?

Published online by Cambridge University Press:  07 January 2016

Leandro Reus Rodrigues Perez*
Affiliation:
Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil Laboratório de Pesquisa em Resistência Bacteriana, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil Hospital Mãe de Deus, Porto Alegre, Brazil
Cícero Gomes Dias
Affiliation:
Hospital Mãe de Deus, Porto Alegre, Brazil Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil
*
Address correspondence to Leandro Reus Rodrigues Perez, PhD, Universidade Federal do Rio Grande do Sul, Faculdade de Farmácia, 2752 Ipiranga Avenue, 90610-000, Porto Alegre–RS, Brazil (leandro.reus@gmail.com).
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Abstract

Type
Letters to the Editor
Copyright
© 2016 by The Society for Healthcare Epidemiology of America. All rights reserved 

To the Editor—Carbapenem resistance among enterobacterial species has increased worldwide and the carbapenemase production is by far the main mechanism responsible for the spread into nosocomial settings, particularly in intensive care units.Reference Nordmann, Naas and Poirel 1

Early detection of colonized patients through surveillance cultures is important for the management of patients and to establish infection control practices in order to avoid carbapenemase-producing Enterobacteriaceae (CPE) dissemination. Infections due to CPE are a great concern because these organisms are highly resistant to most antimicrobial agents, leaving only a few therapeutic choices, such as polymyxins.Reference Carmeli, Akova and Cornaglia 2 , Reference Perez 3

In view of this, we conducted a retrospective survey from January to August, 2014, including patients in an adult intensive care unit of a tertiary hospital in Porto Alegre, Southern Brazil, in order to evaluate the incidence of infections by CPE recovered from some clinical sites in previously colonized patients.

Identification of enterobacterial species; determination of minimum inhibitory concentrations for ertapenem, meropenem, imipenem, and polymyxin B; search for any carbapenemase gene; and molecular typing were applied for those CPE isolates that were found in both surveillance and clinical specimens, as previously reported.Reference Perez, Rodrigues and Dias 4

During the period of the study, 149 (24.3%) of the 613 patients were found to be colonized by CPE and in only 10 of them, a CPE was recovered in a clinical specimen, resulting in a 6.7% (10/149; 95% CI, 3.7%–11.9%) cumulative incidence rate of infection.

Table 1 shows the 10 colonized patients with CPE who presented with a subsequent infection with the same microorganism. All these CPE isolates were identified as KPC-2-producing Klebsiella pneumoniae (KPC-2-KP) and all were identical by molecular typing. This finding is due to the high prevalence of a dominant clone KPC-2-KP responsible for maintaining a low endemic level in our institution, as described previously.Reference Perez 5 For these isolates, minimum inhibitory concentrations for all carbapenems were higher than 32 mg/L whereas for polymyxin B they ranged from 0.5 to 48 mg/L (Table 1). It is of note that 6 (60%) of these 10 patients were carrying a polymyxin-resistant KPC-2-KP. In 5 (83.3%) of these 6 patients the presence of a polymyxin-resistant isolate had been previously detected in the surveillance culture.

TABLE 1 Microbiologic Characteristics and Clinical Outcome in Patients Infected With KPC-2-Klebsiella pneumoniae and Previously Colonized With This Same Pathogen

NOTE. MIC, minimum inhibitory concentration.

a Considering ≥4 mg/L as resistant.

b Considering ≤2 mg/L and >2 mg/L as susceptible and resistant, respectively.

Despite the resistance rate for polymyxin B among colonizing KPC-2-KP isolates being only 16.8% during the same period,Reference Perez 3 our results are concerning because patients who presented with prior colonization by a polymyxin-resistant isolate ended up developing infections caused by this microorganism. Importantly, this fact shows the need to implement a rigorous protocol for polymyxin B consumption (widely used for treating infections by carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter baumannii in our intensive care unit patients nowadays). Apart from that, although we have not assessed the mortality rate attributed to KPC-2-KP, this outcome is quite notable in patients infected with it (Table 1).

Colonization with potential pathogens is almost always a prerequisite for the development of nosocomial infections; however, only a minority of colonized patients eventually develops clinical infection. This relation may be influenced by many factors, including pathogen virulence, host defense mechanisms, and antimicrobial exposure. As in ours, only a few studies have addressed progression to infection among colonized patients with CPE, using the recovery from clinical sites as a marker for infection.Reference Giannella, Trecarichi and De Rosa 6 Reference Borer, Saidel-Odes and Eskira 8 Interestingly, our results were similar to these studies, mainly in relation to the incidence rate of infections among colonized patients and the predominance of KPC-2-KP among the CPE isolates. On the other hand, in these studies, no data on polymyxin B resistance was reported.

In conclusion, despite a low incidence of infections by KPC-2-KP in previously colonized patients, a KPC-2-KP predominant clone presenting with a high polymyxin B resistance level has been responsible for most intensive care unit infections due to CPE isolates. Although our results should be validated by further studies, they serve as a warning to prevent the spread of polymyxin-resistant KPC-2-KP by the early detection of carriers, especially among critically ill patients.

ACKNOWLEDGMENTS

Financial support. Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil.

Potential conflicts of interest. Both authors report no conflicts of interest relevant to this article.

Footnotes

Presented in part: 25th European Congress of Clinical Microbiology and Infectious Diseases; Copenhagen, Denmark; April 27, 2015 (abstract no. ECCMD-3386).

References

REFERENCES

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TABLE 1 Microbiologic Characteristics and Clinical Outcome in Patients Infected With KPC-2-Klebsiella pneumoniae and Previously Colonized With This Same Pathogen