Cluster of oseltamivir-resistant 2009 pandemic influenza A (H1N1) virus infections on a hospital ward among immunocompromised patients--North Carolina, 2009

Abstract

Background: Oseltamivir resistance among 2009 pandemic influenza A (H1N1) viruses (pH1N1) is rare. We investigated a cluster of oseltamivir-resistant pH1N1 infections in a hospital ward.

Methods: We reviewed patient records and infection control measures and interviewed health care personnel (HCP) and visitors. Oseltamivir-resistant pH1N1 infections were found with real-time reverse-transcription polymerase chain reaction and pyrosequencing for the H275Y neuraminidase (NA) mutation. We compared hemagglutinin (HA) sequences from clinical samples from the outbreak with those of other surveillance viruses.

Results: During the period 6-11 October 2009, 4 immunocompromised patients within a hematology-oncology ward exhibited symptoms of pH1N1 infection. The likely index patient became febrile 8 days after completing a course of oseltamivir; isolation was instituted 9 days after symptom onset. Three other case patients developed symptoms 1, 3, and 5 days after the index patient. Three case patients were located in adjacent rooms. HA and NA sequences from case patients were identical. Twelve HCP and 6 visitors reported influenza symptoms during the study period. No other pH1N1 isolates from the hospital or from throughout the state carried the H275Y mutation.

Conclusions: Geographic proximity, temporal clustering, presence of H275Y mutation, and viral sequence homology confirmed nosocomial transmission of oseltamivir-resistant pH1N1. Diagnostic vigilance and prompt isolation may prevent nosocomial transmission of influenza.

Figure 1.

A, Gantt chart illustrating key events in illness timeline. B, spot map illustrating the location of confirmed cases of oseltamivir-resistant pandemic influenza A (H1N1) virus (pH1N1) infection within the hematology-oncology ward during the outbreak. Each patient is represented by a color. Each colored line in the Gantt chart represents the date on which a confirmed case patient (A–D) was admitted to the affected ward. Each patient's room within the hematology-oncology ward is indicated by circles with corresponding colors. Bronchoalveolar lavage (BAL) specimens collected from patient A on 15 October 2009 and 27 October 2009, as well as their grown isolates, were tested. One BAL specimen collected from patient B on 14 October 2009 and its grown isolate were also tested. Two nasal wash specimens collected from patient C on 22 October 2009 and 29 October 2009, in addition to a grown isolate, were also tested. Two nasal swab specimens collected from patient D on 14 October and 23 October 2009 and a grown virus were tested.

Figure 2.

Phylogenetic tree illustrating genetic relation between hemagglutinin (HA) of viruses from the outbreak and from specimens obtained in other areas of the hospital and for surveillance ( n = 17). Numbers indicate maximal likelihood value. Scale bar indicates nucleotide substitutions per site. The 2009 pandemic vaccine strain (bold italic), 4 identified oseltamivir-resistant strains from this outbreak (red), strains from two other patients from the same ward before and after the outbreak (green), and 2 strains collected early in the pandemic (italic) are shown. Other strains shown are 9 strains isolated from different localities in North Carolina.