C. Mary Healy

Emergence of New Strains of Methicillin-Resistant Staphylococcus aureus in a Neonatal Intensive Care Unit

BACKGROUND Genetically distinct strains of methicillin-resistant Staphylococcus aureus (MRSA) of community rather than hospital origin have emerged in many areas of the United States. We determined if MRSA strains causing bacteremia in infants treated from birth in a neonatal intensive care unit (NICU) demonstrated the genetic traits of community-associated MRSA. METHODS A retrospective cohort study was conducted among NICU infants with bacteremia due to MRSA during 2003 in a large tertiary care center NICU in Houston. MRSA isolates were characterized by antimicrobial susceptibility testing and staphylococcal cassette chromosome mec (SCCmec) typing by polymerase chain reaction. All MRSA cases were reviewed for clinical severity of infection and outcome. RESULTS During 2003, a total of 8 (47%) of 17 infants with bacteremia due to S. aureus had MRSA infection. Isolates from 6 (75%) of these 8 infants carried the SCCmec genes (class B mec and ccr2) that are characteristic of community MRSA; 4 isolates were type IVa. All 6 isolates were resistant to beta-lactam antibiotics and erythromycin; 1 was also resistant to clindamycin. One isolate was nontypeable, and another carried the SCCmec type II gene (typical of hospital-associated strains) and was susceptible only to vancomycin. Seven (88%) of 8 infants presented in septic shock. Despite initial treatment with vancomycin, 3 (38%) died, and 3 survivors had complications requiring prolonged antimicrobial therapy; these 6 infants had MRSA isolates with genetic characteristics of isolates of community origin. CONCLUSIONS Community-associated MRSA strains have emerged as a significant cause of sepsis in neonates hospitalized in NICU since birth and have caused disseminated infection with substantial morbidity and mortality.

Prevalence of Pertussis Antibodies in Maternal Delivery, Cord, and Infant Serum

BACKGROUND Passively acquired maternal antibodies protect infants from many pathogens. With increasing reports of infant pertussis, we evaluated pertussis antibodies in maternal-infant paired sera from 1999-2000. METHODS Antibodies to pertussis toxin (PT), filamentous hemagglutinin (FHA), and fimbrial proteins (FIM) were measured by validated IgG-specific enzyme-linked immunosorbant assay (ELISA) in 64 maternal-umbilical cord serum pairs and in 61 of 64 infant sera. Geometric mean concentrations (GMCs) of pertussis antibodies and cord : maternal GMC ratios were calculated. RESULTS Mean maternal age and gestation were 29.7 years (range, 19-42) and 39.3 weeks (range, 35.6-40.9), and 81% of mothers were white. GMCs of maternal antibodies at delivery (ELISA units/mL) were 2.4 for PT, 6.9 for FHA, and 13 for FIM. Cord GMCs were 169%, 178%, and 157% of maternal delivery values for PT, FHA, and FIM, respectively, demonstrating active placental transfer (P<.001). Pertussis-specific IgG values for each antigen decayed to below the threshold of detection by age 2 months. CONCLUSIONS Despite efficient placental transfer, low maternal pertussis antibody levels and their rapid decay in infant sera leave infants with little humoral protection against pertussis. These data support the rationale for maternal or neonatal immunization, with acellular pertussis vaccines, to prevent life-threatening pertussis in early infancy.

Importance of Timing of Maternal Combined Tetanus, Diphtheria, and Acellular Pertussis (Tdap) Immunization and Protection of Young Infants

BACKGROUND Pertussis booster vaccine (Tdap) recommendations assume that pertussis-specific antibodies in women immunized preconception, during, or after previous pregnancies persist at sufficient levels to protect newborn infants. METHODS Pertussis-specific immunoglobulin G (IgG) was measured by IgG-specific enzyme-linked immunosorbent assay (ELISA) in maternal-umbilical cord serum pairs where mothers received Tdap during the prior 2 years. Geometric mean concentrations (GMCs) of pertussis antibodies and cord-maternal GMC ratios were calculated. RESULTS One hundred five mothers (mean age, 25.3 years [range, 15.3-38.4 years]; mean gestation, 39 weeks [range, 37-43 weeks]) immunized with Tdap vaccine a mean of 13.7 months (range, 2.3-23.9 months) previously were included; 72 (69%) had received Tdap postpartum, 31 at a routine healthcare visit and 2 as contacts of another newborn. There was no difference in GMCs for pertussis-specific IgG in maternal delivery or infant cord sera for women immunized before (n = 86) or during (n = 19) early pregnancy. Placental transport of antibodies was 121%-186% from mothers immunized before and during pregnancy, respectively. Estimated GMC of IgG to pertussis toxin was <5 ELISA units (EU)/mL at infant age 2 months (start of infant immunization series). More infants of mothers immunized during pregnancy had pertussis toxin levels estimated to be higher than the lower limit of quantitation of the assay (4 EU/mL) through age 2 months (52% vs 38%; P = .34). CONCLUSIONS Infants of mothers immunized preconception or in early pregnancy have insufficient pertussis-specific antibodies to protect against infection. Maternal immunization during the third trimester, immunization of other infant contacts, and reimmunization during subsequent pregnancies may be necessary.

Fluconazole Prophylaxis in Extremely Low Birth Weight Neonates Reduces Invasive Candidiasis Mortality Rates Without Emergence of Fluconazole-Resistant Candida Species

OBJECTIVE. We evaluated the impact of fluconazole prophylaxis for extremely low birth weight infants on invasive candidiasis incidence, invasive candidiasis-related mortality rates, and fluconazole susceptibility of Candida isolates. METHODS. Extremely low birth weight infants <5 days of age, except those with liver dysfunction, were eligible for fluconazole prophylaxis. NICU infants (all birth weights) with invasive candidiasis between April 2002 and March 2006 were compared with those with invasive candidiasis before fluconazole prophylaxis (2000–2001). RESULTS. Twenty-two infants had invasive candidiasis (all candidemia) during fluconazole prophylaxis; before fluconazole prophylaxis, there were 19 cases (candidemia: 17 cases; meningitis: 2 cases). Invasive candidiasis incidence in NICU infants decreased from 0.6% (19 of 3012 infants) before fluconazole prophylaxis to 0.3% (22 of 6393 infants) in 2002–2006 and that in extremely low birth weight infants decreased 3.6-fold. No Candida-attributable deaths occurred during 2002–2006 fluconazole prophylaxis, compared with 4 (21%) before fluconazole prophylaxis. The onset of invasive candidiasis was later during 2002–2006 (23.5 vs 12 days), but risk factors were similar. The invasive candidiasis species distribution remained stable. Of 409 infants who received fluconazole prophylaxis, 119 (29%) received 42 days. Shorter fluconazole prophylaxis duration was related to intravenous access no longer being necessary in 242 cases (59%), noninvasive candidiasis-related death in 29 (7%), hospital transfer in 8 (2%), invasive candidiasis diagnosis in 8 (2%), and transient increase in serum transaminase levels in 4 (1%). One hundred twenty-seven infants (31%) who received fluconazole prophylaxis developed cholestasis during hospitalization, two thirds of whom had other predisposing conditions. On multivariate logistic regression necrotizing enterocolitis and increasing days of total parenteral nutrition, but not increasing number of doses on days of fluconazole, were significantly associated with the development of cholestasis. CONCLUSION. During 4 years of fluconazole prophylaxis, the incidence of invasive candidiasis and invasive candidiasis-associated mortality rates in extremely low birth weight infants were reduced significantly, without the emergence of fluconazole-resistant Candida species.

Features of Invasive Staphylococcal Disease in Neonates

Objective. Most clinical descriptions of invasive staphylococcal disease (ISD) in neonates date from before the mid-1980s, when neonatal viability and intensive care differed substantially from current standards. We aimed to describe the contemporary incidence, clinical features, and outcome of infants with ISD in a neonatal intensive care unit. Methods. A retrospective cohort study was conducted of infants who had ISD and were in the neonatal intensive care unit of the Womans Hospital of Texas, Houston, from January 2000 to June 2002. Confirmed ISD was defined as clinical sepsis and Staphylococcus aureus (SA) isolated from ≥1 blood culture (BC) or a sterile body site excluding urine or coagulase-negative staphylococci (CoNS) isolated from ≥2 BC or from 1 BC and a sterile body site. Probable ISD was defined as CoNS isolated from 1 BC or a sterile body site for which clinical and laboratory data review by 3 infectious disease specialists indicated that antimicrobial treatment was appropriate. Confirmed and combined confirmed plus probable cases were analyzed. Results. A total of 149 episodes (83 confirmed [39 SA, 44 CoNS], 66 probable) in 137 infants (mean gestational age [GA]: 27.6 weeks [22.4–36.4]; mean birth weight: 981 g [350–2995]) were reviewed. Four (3%) infants had early-onset infection (2 SA, 2 CoNS). Median age at infection onset was similar (17 days SA; 18 days CoNS). Intravascular catheters (IVC) were in situ in a minority of infants with ISD episodes (38% SA, 43% CoNS). CoNS more than SA infections were associated with very low birth weight (<1500 g), lower GA, a history of more IVCs and concurrent total parenteral nutrition, but IVC and parenteral nutrition days were similar. By multivariate analysis correcting for birth weight and complications of prematurity, hypoxia at the time of sepsis evaluation was significantly associated with CoNS and hypotension with SA infections; other clinical features were similar. Methicillin-resistant SA caused 8% of SA infections. Among bacteremic infants, SA more frequently than CoNS involved ≥2 sites. Overall, SA had more focal complications (primarily bone and joint) than CoNS, resulting in a 2- to 3-fold higher SA-associated morbidity rate. Mortality directly attributable to either organism was similar (5% SA; 5% confirmed, 3% confirmed/probable CoNS). Conclusion. CoNS ISD occurred in smaller, more premature infants than SA and was IVC associated in a minority of cases. Hypoxia and hypotension were the only presenting features that differentiated CoNS and SA. SA-associated morbidity was substantial, but SA infection carried no greater risk of death (5%) than CoNS.

How to communicate with vaccine-hesitant parents.

Development of safe and effective vaccines is one the greatest medical triumphs. However, despite high immunization rates in the United States, 85% of health care providers (HCPs) will have a parent refuse a vaccine for his or her child each year. HCPs have the greatest influence on a parents decision to vaccinate his or her child. To effectively communicate with vaccine-hesitant parents, HCPs must first understand the concerns of parents regarding immunization and understand influences that can lead to misinformation about the safety and effectiveness of vaccines. HCPs should establish an open, nonconfrontational dialogue with vaccine-hesitant parents at an early stage and provide unambiguous, easily comprehensible answers about known vaccine adverse events and provide accurate information about vaccination. Personal stories and visual images of patients and parents affected by vaccine-preventable diseases and reports of disease outbreaks serve as useful reminders of the need to maintain high immunization rates. Ongoing dialogue including provider recommendations may successfully reassure vaccine-hesitant parents that immunization is the best and safest option for their child.

Impact of Maternal Postpartum Tetanus and Diphtheria Toxoids and Acellular Pertussis Immunization on Infant Pertussis Infection

BACKGROUND Mothers often are the source of pertussis illness in young infants. The Centers for Disease Control and Prevention recommend tetanus and diphtheria toxoids and acellular pertussis (Tdap) vaccine for postpartum women before hospital discharge. In January 2008, this recommendation was implemented in a predominantly Hispanic, medically underserved population at Ben Taub General Hospital (BTGH) in Houston (hereafter the intervention population). METHODS A cross-sectional study compared preintervention (July 2000 through December 2007) and postintervention (January 2008 through May 2009) periods. Pertussis diagnosis was determined using International Classification of Diseases, Ninth Revision (ICD-9) codes and microbiology reports from 4 major childrens hospitals in Houston. Only those infants ≤6 months of age with laboratory-confirmed pertussis illness were included. The proportions of pertussis-infected infants born at BTGH in the pre- and postintervention periods were compared. RESULTS Of 514 infants with pertussis, 378 (73.5%) were identified during preintervention and 136 (26.5%) during postintervention years. These groups were similar in age (mean, 79.3 vs 72 days; P = .08), sex (males, 55% vs 52%; P = .48), length of hospitalization (mean, 9.7 vs 10.7 days; P = .62), mortality (2 deaths each; P = .29) and hospital of pertussis diagnosis. After adjustment for age, sex, and ethnicity, the proportions of pertussis-infected infants born at BTGH and potentially protected through maternal postpartum Tdap immunization were similar for the 2 periods (6.9% vs 8.8%; odds ratio, 1.06; 95% confidence interval, 0.5-2.2; P = .87). CONCLUSIONS Immunizing only postpartum mothers with Tdap vaccine did not reduce pertussis illness in infants ≤6 months of age. Efforts should be directed at immunizing all household and key contacts of newborns with Tdap, not just mothers.

Evaluation of the impact of a pertussis cocooning program on infant pertussis infection

Background: Tetanus, diphtheria and acellular pertussis immunization of infant contacts (cocooning) is recommended by the Centers for Disease Control and Prevention to prevent infant pertussis. We determined whether implementing a cocooning program at Ben Taub General Hospital, Houston, reduced severe pertussis in young infants. Methods: Infants ⩽6 months of age, diagnosed with pertussis (determined by International Classification of Diseases, Ninth Revision codes and microbiology records) at 4 hospitals, and born at times when only postpartum women (January 2008 through May 2009) and all infant contacts (June 2009 through August 2011) were offered tetanus, diphtheria and acellular pertussis vaccine at Ben Taub General Hospital were compared with infants born preintervention (May 2004 through December 2007). Results: One hundred ninety-six (49%) infants with pertussis were born preintervention, 140 (35%) during maternal postpartum (PP) and 64 (16%) during cocooning (C) periods. Infants were similar in age at diagnosis (81.2 vs. 71.3 [PP] vs. 72.5 [C] days; P 0.07), sex (male 59% vs. 51% [PP] vs. 48% [C]; P 0.17), hospitalization (68% vs. 71% [PP] vs. 78% [C]; P 0.27) and outcome (2 deaths in the PP period; P 0.15), but more were admitted to intensive care units during cocooning (24% vs. 35% [PP] vs. 68% [C]; P < 0.001). Similar proportions of infants were born at Ben Taub General Hospital throughout the study (8% vs. 9% [PP] vs. 5% [C]; P 0.53). Conclusions: Postpartum immunization and cocooning did not reduce pertussis illness in infants ⩽6 months of age. Efforts should be directed toward increasing tetanus, diphtheria and acellular pertussis immunization during pregnancy, combined with cocooning, to reduce life-threatening young infant pertussis.

Parent and provider perspectives on immunization: are providers overestimating parental concerns?

OBJECTIVES Data are limited on whether providers understand parental attitudes to recommended childhood immunizations. We determined parental attitudes and assessed how accurately providers estimated parental opinions. METHODS Survey of parents and providers (pediatricians, nurses, medical assistants) in randomly selected practices in Houston, Texas. Surveys assessed demographics, perceptions of immunization importance, safety and efficacy, and acceptability of vaccine delivery. Providers estimated parental responses. RESULTS 401 parents (82% mothers, 12% fathers, 6% other) and 105 providers participated. Parents thought vaccines were important for health (median score 9.5; 0=not important, 10=extremely important) but also were concerned regarding vaccine safety and side effects (8.9 on 0-10 scale). 309 (77%) agreed that vaccines effectively prevent disease. Route of administration mattered to 147 (37%), who preferred injection (9.0) over oral (7.3) or intranasal (4.8) routes. Although parents would prefer three or fewer injections per visit, preventing more diseases (189 [47.6%]) was more important than number of injections (167 [42.3%]) when deciding the number of vaccines allowed per visit. White parents rated vaccines less important in preventing some illnesses than did non-white (P≤0.006 for meningitis, hepatitis, HPV, influenza and rotavirus) and rated number of injections per visit more important than number of diseases prevented (51.6% white versus 34.2% non-white; P 0.002). Providers underestimated parental attitudes toward vaccine importance (particularly influenza and HPV), and overestimated the proportion of parents who thought route of administration mattered (63%) and that number of injections per visit was the most important factor (76%) around parental vaccine decisions (P<0.001 for parent-provider mismatch). CONCLUSIONS Most surveyed parents believe vaccines are important for child health and rate disease prevention higher than number of injections entailed. Providers underestimate the importance of some vaccines to parents and overestimate parental concerns regarding route of administration. Future research should focus on how this mismatch impacts parental vaccine decisions.

Pertussis immunization in a high-risk postpartum population.

We provided CDC recommended postpartum tetanus, diphtheria, acellular pertussis (Tdap) immunization to medically underserved, uninsured women in Houston through a standing order protocol. From January 7-April 30, 2008, 1129 of 1570 (72%) postpartum women (93% Hispanic; 11% < or = 19 years) received Tdap before hospital discharge. Tdap uptake was 96.2% in women without self-reported contraindications. Recall of immunization history was inaccurate in 32% of unimmunized women who reported receiving antepartum immunization. Black women refused Tdap more often than other ethnicities (24% versus 8%; P=0.003). Postpartum Tdap immunization was successfully implemented in a high-risk population through a standing order protocol. Barriers to postpartum immunization include inaccurate immunization history and the need for ongoing targeted education.