Transmission Dynamics of Carbapenemase-Producing Klebsiella Pneumoniae and Anticipated Impact of Infection Control Strategies in a Surgical Unit

<div><h3>Background</h3><p>Carbapenemase-producing <em>Klebsiella pneumoniae</em> (CPKP) has been established as important nosocomial pathogen in many geographic regions. Transmission from patient to patient via the hands of healthcare workers is the main route of spread in the acute-care setting.</p> <h3>Methodology/Principal Findings</h3><p>Epidemiological and infection control data were recorded during a prospective observational study conducted in a surgical unit of a tertiary-care hospital in Greece. Surveillance culture for CPKP were obtained from all patients upon admission and weekly thereafter. The Ross-Macdonald model for vector-borne diseases was applied to obtain estimates for the basic reproduction number <em>R₀</em> (average number of secondary cases per primary case in the absence of infection control) and assess the impact of infection control measures on CPKP containment in endemic and hyperendemic settings. Eighteen of 850 patients were colonized with CPKP on admission and 51 acquired CPKP during hospilazation. <em>R₀</em> reached 2 and exceeded unity for long periods of time under the observed hand hygiene compliance (21%). The minimum hand hygiene compliance level necessary to control transmission was 50%. Reduction of 60% to 90% in colonized patients on admission, through active surveillance culture, contact precautions and isolation/cohorting, in combination with 60% compliance in hand hygiene would result in rapid decline in CPKP prevalence within 8–12 weeks. Antibiotics restrictions did not have a substantial benefit when an aggressive control strategy was implemented.</p> <h3>Conclusions/Significance</h3><p>Surveillance culture on admission and isolation/cohorting of colonized patients coupled with moderate hand hygiene compliance and contact precautions may lead to rapid control of CPKP in endemic and hyperendemic healthcare settings.</p> </div

Model of indirect transmission of CPKP between patients through health-care workers (HCWs) and impact of intervention measures.

<p>A. Model of indirect transmission of CPKP between patients through health-care workers (HCWs) who act as vectors. Solid lines depict the movement to/from the four population groups and dashed lines depict the transmission between patients and HCWs B. The impact of intervention measures in the transmission process: hand washing (allows the decontamination of HCWs), staff cohorting (reduces patients mixing with contaminated HCWs), antibiotic restriction (reduces the probability of CPKP colonization per contact with contaminated HCW), screening and isolation of colonized admissions.</p

Impact of infection control measures on the prevalence of CPKP colonization in an endemic setting.

<p>One CPKP colonized patient enters the surgical unit on day 0 and the only infection control measure applied during the first 30 days is hand hygiene compliance (<i>p</i> = 21%). The impact of various infection control strategies implemented since day 30 on CPKP colonization prevalence was simulated (the mean of 1,000 simulations is shown). The evaluated scenarios include: <b>1.</b> adopt no additional infection control measures (hand hygiene compliance <i>p</i> = 21%), <b>2.</b> increase <i>p</i> to 60%, <b>3.</b> increase <i>p</i> to 80%, <b>4.</b> increase <i>p</i> to 60% and reduce colonization prevalence on admission of CPKP by 60% (through active surveillance and subsequent isolation or strict contact precautions for positive patients), <b>5.</b> increase <i>p</i> to 60% and reduce colonization prevalence on admission of CPKP by 90%, <b>6.</b> increase <i>p</i> to 80% and reduce colonization prevalence on admission of CPKP by 90%. Dashed lines (<b>- - -</b>) correspond to the above scenarios with the addition of 50% reduction in the duration of antibiotic usage during patients' stay in the unit (assuming a relative risk associated with antibiotic use equal to 3).</p

Bimonthly predicted effective reproduction number <i>R(p)</i> and observed occupancy within the surgical unit. A.

<p>Bimonthly predicted effective reproduction number <i>R(p)</i> (under the observed hand hygiene compliance rate of <i>p</i> = 21% during the study period) and the corresponding basic reproduction number <i>R₀</i>. Values of <i>R(p)</i>>1 (dotted line) indicate the potential for an epidemic to occur. <b>B.</b> Observed occupancy within the surgical unit during the study period (monthly estimates).</p

Observed number of patients with CPKP and model fit.

<p>Observed cumulative number of CPKP colonized patients (admissions and colonizations within the unit), CPKP colorizations within the unit and CPKP colonized admissions (solid lines) along with the corresponding model fit (dashed lines).</p

Parameter estimates used in the model of CPKP transmission.

<p>Parameter estimates used in the model of CPKP transmission.</p

Impact of infection control measures on the prevalence of CPKP colonization in an hyperendemic setting.

<p>Infection control measures start on day 0 where a high colonization prevalence of 21% was assumed. The evaluated scenarios include: <b>1</b>. Hand hygiene compliance <i>p</i> = 60%, <b>2.... </b><i>p = </i>80%, <b>3.... </b><i>p</i> = 60% and reduce colonization prevalence on admission of CPKP by 60% (through active surveillance and subsequent isolation or strict contact precautions for positive patients), <b>4.... </b><i>p</i> = 60% and reduce colonization prevalence on admission of CPKP by 90%, <b>5.... </b><i>p</i> = 80% and reduce colonization prevalence on admission of CPKP by 90%. Dashed lines (<b>- - -</b>) correspond to the above scenarios with the addition of 50% reduction in the duration of antibiotic usage during patients' stay in the unit (assuming a relative risk associated with antibiotic use equal to 3).</p

Impact of relaxing the infection control measures on the prevalence of CPKP colonization in an endemic setting.

<p>One CPKP colonized patient enters the surgical unit on day 0 and the only infection control measure applied during the first 30 days is hand hygiene compliance (<i>p</i> = 21%). Infection control measures are implemented during three months (day 30 - day 120). After day 120, only hand hygiene measures with 60% compliance are implemented. The evaluated scenarios during day 30-day 120 include: <b>1</b>. Hand hygiene compliance <i>p</i> = 60%, <b>2.... </b><i>p = </i>80%, <b>3.... </b><i>p</i> = 60% and reduce colonization prevalence on admission of CPKP by 60% (through active surveillance and subsequent isolation or strict contact precautions for positive patients), <b>4.... </b><i>p</i> = 60% and reduce colonization prevalence on admission of CPKP by 90%, <b>5.... </b><i>p</i> = 80% and reduce colonization prevalence on admission of CPKP by 90%.</p

Contour plots showing how generation time (<i>T</i>), basic reproductive number (<i>R</i>₀) and the proportion of transmitters in the population (<i>u</i>) co-vary.

<p>Gray bands highlight different values of <i>u</i>. The area between the white dashed lines represents <i>R</i>₀ values estimated by sensitivity analysis of mortality and recovery rate (<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002876#pcbi.1002876.s007" target="_blank">Table S3</a>). The area between the yellow dashed lines represents the 95% confidence limits of <i>R</i>₀ values estimated assuming 40 years of infectivity and 70 years of life expectancy. The black dots show the maximum <i>T</i> value for each subtype, which is defined by empirical values for <i>u</i> and the median values of <i>R</i>₀ (see text).</p

Cumulative proportion of onward infection versus the infected population ranked by the number of secondary infections they create.

<p>20% of onward infections is indicated with a grey horizontal line. The proportion of the population that generates 80% of onward infections is shown by a vertical dashed line. HCV subtype 1a is close to the 80-20 rule (i.e. 80% of the infections are caused by the most infectious 18%).</p