Luis Alba

Antimicrobial Susceptibility and Synergy Studies of Burkholderia cepacia Complex Isolated from Patients with Cystic Fibrosis

ABSTRACT Susceptibility (18 antimicrobial agents including high-dose tobramycin) and checkerboard synergy (23 combinations) studies were performed for 2,621 strains of Burkholderia cepacia complex isolated from 1,257 cystic fibrosis patients. Minocycline, meropenem, and ceftazidime were the most active, inhibiting 38%, 26%, and 23% of strains, respectively. Synergy was rarely noted (range, 1% to 15% of strains per antibiotic combination).

Epidemiology of candidemia at a Children's hospital, 2002 to 2006.

Background: There are few recent studies evaluating trends in the epidemiology of candidemia including changes in species or utilization of antifungal agents in children. Methods: We performed a retrospective case series of candidemia at our childrens hospital from 2002 to 2006. Our objectives were to study trends in the rates of candidemia, demographic characteristics, Candida species, antifungal susceptibility, and antifungal utilization. These data were obtained from the electronic medical records. Results: There were 203 episodes of candidemia in 154 subjects. During the study period, the average rate of candidemia was 5.52 per 1000 patient-discharges and did not change throughout the study. The mean and median ages of subjects were 3 years versus 9 months, respectively, and 38% were less than 3 months of age. Gastrointestinal disorders were a common comorbid condition (33%), especially for subjects with multiple episodes of candidemia. Overall, Candida parapsilosis and Candida albicans caused 43% and 26% of episodes, respectively, and candidemia caused by Candida glabrata (5.3%–23%) and Candida krusei (0%–8.5%) increased during the study. Ninety-eight percent of C. albicans and C. parapsilosis isolates remained susceptible to all antifungal drugs. From 2003–2006, the use of antifungal agents increased from 79 days to 150 days per 1000 hospital-days. Conclusions: While antifungal use at our hospital increased, candidemia rates remained stable. C. parapsilosis was the most common species but other non–C. albicans species increased during the study period. Local epidemiology should be monitored in pediatric populations for potential impact on management strategies.

Barriers to adherence to cystic fibrosis infection control guidelines

In 2003, the American Cystic Fibrosis (CF) Foundation published revised, evidence‐based guidelines for infection control. We sought to assess potential barriers to adherence to these guidelines experienced by health care professionals (HCPs) caring for CF patients.

Staphylococcus aureus nasal colonization among pediatric cystic fibrosis patients and their household contacts.

Background: Little is known about the prevalence of Staphylococcus aureus nasal colonization and the epidemiology of methicillin-susceptible and methicillin-resistant S. aureus (MRSA) among cystic fibrosis (CF) patients and their household members. Objectives: We sought to determine the epidemiology of S. aureus among children and adolescents with CF and their household members. Methods: Three CF centers enrolled case subjects with at least 1 MRSA-positive respiratory tract culture from 2001 to 2006 and control subjects with MRSA-negative cultures. S. aureus isolates from the anterior nares of CF subjects and their household members were assessed for staphylococcal chromosomal cassette (SCC) mec type. Strain similarity was determined by pulsed-field gel electrophoresis. Results: S. aureus nasal colonization occurred in 52.4% (22/42), 27.0% (17/63), and 25.0% (72/288) of case, control, and household participants, respectively. Case subjects and their contacts were more likely to harbor MRSA in their nares and be from a multipatient CF family. Of 31 MRSA strains, 10 (32.3%) were SCCmec type IVa, associated with community-acquisition. Overall, 27.6% of 98 households had ≥2 members colonized with closely related isolates. Household members were equally likely to be colonized with closely related strains of MRSA (20/31, 65%) versus MSSA (38/80, 48%). Conclusions: This study demonstrated that household members of CF children harbor both MSSA and MRSA, including CA-MRSA, and that S. aureus is transmitted within CF households. Carriage of S. aureus by household members of CF children may have implications for infection control and treatment strategies. Future studies should monitor the distribution and virulence of SCCmecA types in patients with CF.

Infection control knowledge, attitudes, and practices among cystic fibrosis patients and their families.

In 2003, the Cystic Fibrosis (CF) Foundation in the United States published evidence‐based infection control guidelines and distributed these to CF care centers. However, it is unclear how well the guidelines have been disseminated to patients and families, how well patients and families understand the principles of infection control, and what barriers they experience implementing the guidelines.

Risk factors and Outcomes of Infections Caused by Extremely Drug-Resistant Gram-Negative Bacilli in Patients Hospitalized in Intensive Care Units

BACKGROUND Extremely drug-resistant gram-negative bacilli (XDR-GNB) increasingly cause health care-associated infections (HAIs) in intensive care units (ICUs). METHODS A matched case-control (1:2) study was conducted from February 2007 to January 2010 in 16 ICUs. Case and control subjects had HAIs caused by GNB susceptible to ≤1 antibiotic versus ≥2 antibiotics, respectively. Logistic and Cox proportional hazards regression assessed risk factors for HAIs and predictors of mortality, respectively. RESULTS Overall, 103 case and 195 control subjects were enrolled. An immunocompromised state (odds ratio [OR], 1.55; P = .047) and exposure to amikacin (OR, 13.81; P < .001), levofloxacin (OR, 2.05; P = .005), or trimethoprim-sulfamethoxazole (OR, 3.42; P = .009) were factors associated with XDR-GNB HAIs. Multiple factors in both case and control subjects significantly predicted increased mortality at different time intervals after HAI diagnosis. At 7 days, liver disease (hazard ratio [HR], 5.52), immunocompromised state (HR, 3.41), and bloodstream infection (HR, 2.55) predicted mortality; at 15 days, age (HR, 1.02 per year increase), liver disease (HR, 3.34), and immunocompromised state (HR, 2.03) predicted mortality; and, at 30 days, age (HR, 1.02 per 1-year increase), liver disease (HR, 3.34), immunocompromised state (HR, 2.03), and hospitalization in a medical ICU (HR, 1.85) predicted mortality. CONCLUSION HAIs caused by XDR-GNB were associated with potentially modifiable factors. Age, liver disease, and immunocompromised state, but not XDR-GNB HAIs, were associated with mortality.

In vitro activity of doripenem alone and in multi-agent combinations against extensively drug-resistant Acinetobacter baumannii and Klebsiella pneumoniae

Carbapenems are increasingly needed to treat infections caused by drug-resistant gram-negative bacilli (GNB), but carbapenem resistance is increasing. We evaluated the activity of doripenem by broth microdilution against 96 extensively drug-resistant (XDR) Acinetobacter baumannii and Klebsiella pneumoniae isolates from patients with hospital-associated infections. All isolates were non-susceptible to doripenem, but ≥ 1 doripenem combination demonstrated synergy (fractional inhibitory concentration index: ≤ 0.5 for 2 agents, ≤ 0.75 for 3 agents) against 7 (15%) A. baumannii and 23 (48%) K. pneumoniae isolates; doripenem with rifampin and/or polymyxin B were most active. As doripenem has unique potential for use in prolonged infusions, suggested pharmacodynamic (PD) breakpoints range from 2-8 μg/mL; synergistic activity was found for higher proportions of XDR-GNB at higher PD breakpoints with doripenem with amikacin or with rifampin. The clinical utility of these observations requires further study, as treatment options for XDR-GNB infections are limited.

MoSAIC: Mobile Surveillance for Acute Respiratory Infections and Influenza-Like Illness in the Community

Surveillance for acute respiratory infection (ARI) and influenza-like illness (ILI) relies primarily on reports of medically attended illness. Community surveillance could mitigate delays in reporting, allow for timely collection of respiratory tract samples, and characterize cases of non–medically attended ILI representing substantial personal and economic burden. Text messaging could be utilized to perform longitudinal ILI surveillance in a community-based sample but has not been assessed. We recruited 161 households (789 people) in New York City for a study of mobile ARI/ILI surveillance, and selected reporters received text messages twice weekly inquiring whether anyone in the household was ill. Home visits were conducted to obtain nasal swabs from persons with ARI/ILI. Participants were primarily female, Latino, and publicly insured. During the 44-week period from December 2012 through September 2013, 11,282 text messages were sent. In responses to 8,250 (73.1%) messages, a household reported either that someone was ill or no one was ill; 88.9% of responses were received within 4 hours. Swabs were obtained for 361 of 363 reported ARI/ILI episodes. The median time from symptom onset to nasal swab was 2 days; 65.4% of samples were positive for a respiratory pathogen by reverse-transcriptase polymerase chain reaction. In summary, text messaging promoted rapid ARI/ILI reporting and specimen collection and could represent a promising approach to timely, community-based surveillance.

Incidence, Risks, and Types of Infections in Pediatric Long-term Care Facilities

Importance The population of infants, children, and adolescents cared for at pediatric long-term care facilities is increasing in complexity and size and thus consumes substantial health care resources. Infections are a significant cause of morbidity and mortality in this population, but few recent data describe their incidence and effects. Objectives To describe the types of infections diagnosed in residents of pediatric long-term care facilities, calculate infection rates, and identify risk factors for respiratory tract infections (RTIs). Design, Setting, and Participants This prospective cohort study, which was part of a larger trial called Keep It Clean for Kids, was conducted from September 1, 2012, to December 31, 2015, at 3 pediatric long-term care facilities in New York. Residents of the facilities who were 21 years or younger and either residents or admitted during the study period (n = 717) were enrolled in the study. Medical records were reviewed to identify infections diagnosed by site clinicians. Main Outcomes and Measures Incidence of infections, such as RTIs; skin and soft-tissue infections; chronic comorbid conditions, including neurologic and respiratory disorders; and device use, including gastrostomy tubes and tracheostomies, was determined. Risk factors for RTIs were assessed by generalized linear mixed method regression modeling. Results The 717 residents had a median (interquartile range) age at enrollment of 2.6 (0.4-9.1) years; 358 (49.9%) were male. Four hundred twenty-eight residents (59.7%) had feeding tubes and 215 (30.0%) had tracheostomies. Most chronic comorbid conditions were musculoskeletal or ambulation (532 residents [74.2%]), neurologic (505 [70.4%]), respiratory (361 [50.3%]), and gastrointestinal (230 [32.1%]) disorders, and 460 residents (64.2%) had 4 or more chronic comorbid conditions. Site clinicians diagnosed 2052 infections during the 3-year study period. Respiratory tract infections were most common and were diagnosed in 1291 residents (62.9%). The overall infection rate was 5.3 infections per 1000 resident-days, and RTI rates were 3.3 infections per 1000 resident-days. Overall infection rates and rates of RTI, skin and soft-tissue infection, urinary tract infection, and bloodstream infection varied among the 3 sites. In the multivariable model, younger age (incidence rate ratio [IRR], 1.05; 95% CI, 1.03-1.06), increased number of chronic comorbid conditions (IRR, 1.12; 95% CI, 1.06-1.19), and the use of feeding tubes (IRR, 1.34; 95% CI, 1.03-1.64) and tracheostomies (IRR, 1.40; 95% CI, 1.17-1.69) were associated with RTIs. Conclusions and Relevance In this study, RTIs were the most common infections diagnosed, but modifiable risk factors for RTIs were not identified. Future work should focus on optimizing infection prevention and control strategies to reduce infections, particularly RTIs, in the pediatric long-term care population.

Colonization With Antimicrobial-Resistant Gram-Negative Bacilli at Neonatal Intensive Care Unit Discharge

Background The epidemiology of the colonization of infants with antimicrobial-resistant Gram-negative bacilli (GNB) at discharge from the neonatal intensive care unit (NICU) is not well understood. Methods A multicenter study in which rectal surveillance samples for culture were obtained at NICU discharge from infants hospitalized ≥14 days was performed. Factors associated with colonization with GNB resistant to gentamicin, third/fourth-generation cephalosporin agents, or carbapenem agents were assessed by using a fixed-effects model. Results Of these infants, 9% (119 of 1320) were colonized with ≥1 antimicrobial-resistant GNB. Prolonged treatment (≥10 days) with meropenem or third/fourth-generation cephalosporin agents or treatment for ≥5 days with a β-lactam/β-lactamase combination agent were associated with an increased risk of colonization with GNB resistant to gentamicin. Surgery and ≥5 days of treatment with third/fourth-generation cephalosporin agents, a β-lactam/β-lactamase combination agent, or metronidazole were associated with an increased risk of colonization with GNB resistant to third/fourth-generation cephalosporin agents. Female sex and prolonged treatment (≥10 days) with meropenem were associated with colonization with GNB resistant to carbapenem agents. Conclusions Prolonged treatment with broad-spectrum antibiotics was associated with the colonization of infants with antimicrobial-resistant GNB within 7 days of NICU discharge. These findings suggest the potential for dissemination of resistant GNB from colonized infants to other NICUs, the community, or pediatric long-term care facilities. Antimicrobial stewardship efforts aimed at improving appropriate antibiotic use could have a beneficial effect on the emergence of antimicrobial-resistant GNB in the NICU population.