Debra L. Palazzi

Bacterial Sepsis and Meningitis

Bacterial sepsis in the neonate is a clinical syndrome characterized by systemic signs of infection and accompanied by bacteremia in the first month of life. Meningitis in the neonate usually is a sequela of bacteremia and is discussed in this chapter because meningitis and sepsis typically share a common cause and pathogenesis. Infections of the bones, joints, and soft tissues and of the respiratory, genitourinary, and gastrointestinal tracts can be accompanied by bacteremia, but the cause, clinical features, diagnosis, and management of these infections are sufficiently different to warrant separate discussions. Sepsis and meningitis caused by group B Streptococcus, Staphylococcus aureus, Neisseria gonorrhoeae, Listeria monocytogenes, Salmonella species, and Mycobacterium tuberculosis are described in other chapters.

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.

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.

Hemophagocytic Syndrome in Children: An Important Diagnostic Consideration in Fever of Unknown Origin

To study the evolution of hemophagocytic syndrome (HPS) in children, we performed a retrospective review of 19 patients (median age, 17.4 months) in whom an infectious diseases consultation was requested at Texas Childrens Hospital during the period of September 1991 through September 2001. Clinical findings consistent with HPS most frequently presented during days 6-14 of illness, concomitant with laboratory abnormalities. Fever was present for a median of 19 days before the diagnosis of HPS. Elevated serum lactate dehydrogenase and ferritin levels were noted in all patients. An infectious agent was identified in 42% of patients; 16% were found to have immunologic or vasculitic disease. HPS is a rare but often fatal disease that can initially present as fever of unknown origin with varying clinical findings, and it can be recognized by physicians who are familiar with the evolution of HPS. It is likely that many of these cases remain undiagnosed because of the HPSs rapidly fatal course.

Results from a Prospective, International, Epidemiologic Study of Invasive Candidiasis in Children and Neonates

Background: Candida species are the third most common cause of pediatric health care–associated bloodstream infection in the United States and Europe. To our knowledge, this report from the International Pediatric Fungal Network is the largest prospective, multicenter observational study dedicated to pediatric and neonatal invasive candidiasis. Methods: From 2007 to 2011, we enrolled 196 pediatric and 25 neonatal patients with invasive candidiasis. Results: Non-albicans Candida species predominated in pediatric (56%) and neonatal (52%) age groups, yet Candida albicans was the most common species in both groups. Successful treatment responses were observed in pediatric (76%) and neonatal patients (92%). Infection with Candida parapsilosis led to successful responses in pediatric (92%) and neonatal (100%) patients, whereas infection with Candida glabrata was associated with a lower successful outcome in pediatric patients (55%). The most commonly used primary antifungal therapies for pediatric invasive candidiasis were fluconazole (21%), liposomal amphotericin B (20%) and micafungin (18%). Outcome of pediatric invasive candidiasis was similar in response to polyenes (73%), triazoles (67%) and echinocandins (73%). The most commonly used primary antifungal therapies for neonatal invasive candidiasis were fluconazole (32%), caspofungin (24%) and liposomal amphotericin B (16%) and micafungin (8%). Outcomes of neonatal candidiasis by antifungal class again revealed similar response rates among the classes. Conclusions: We found a predominance of non-albicans Candida infection in children and similar outcomes based on antifungal class used. This international collaborative study sets the foundation for large epidemiologic studies focusing on the unique features of neonatal and pediatric candidiasis and comparative studies of therapeutic interventions in these populations.

Group B Streptococcal Colonization and Serotype-Specific Immunity in Healthy Elderly Persons

BACKGROUND The burden from group B streptococcal (GBS) disease in elderly persons (age, >or=65 years) has increased. Rates of colonization and prevalence of antibodies against capsular polysaccharides (CPS) that might confer protection against invasive GBS disease in such persons are not defined. METHODS A cross-sectional survey was conducted in an outpatient setting in Houston. GBS colonization rates in this convenience sample were assessed by self-obtained vaginal and rectal specimens (for women) and rectal and urine specimens (for men). The CPS type distribution among GBS isolates was determined, and CPS-specific antibodies against GBS types Ia, Ib, II, III, and V were quantified by enzyme-linked immunosorbent assays. RESULTS The GBS colonization rate among 254 healthy elderly participants (mean age, 73 years) was 21.7%. CPS types Ia (22.8%), III (12.3%), and V (47.3%) predominated, and 12.3% of colonizing isolates were nontypeable. Random selection of 1 member of 33 participating married couples did not alter the overall colonization rate (21.7%) or GBS serotype distribution. The geometric mean concentrations of CPS-specific IgG in serum specimens were low and were significantly lower for GBS type V, compared with other serotypes (P<.001). CONCLUSIONS Adults >or=65 years of age are colonized with GBS at a rate similar to that of younger persons, but older adults are significantly more likely to carry type V, the leading cause of invasive disease in elderly persons, and to lack type V CPS-specific serum IgG. The CPS of type V GBS should be included in candidate GBS vaccines so that adults >or=65 years of age theoretically could be protected against invasive disease.

A report of three cases and review of intrauterine herpes simplex virus infection.

Background: Intrauterine herpes simplex virus (HSV) infection often is omitted from descriptions of neonatal HSV disease. Previous characterizations of intrauterine HSV infection limit manifestations to the triad of cutaneous, central nervous system (CNS), and ophthalmologic findings. We report 3 cases of intrauterine HSV infection and provide a contemporary literature review of this disease. Methods: Cases published between 1963 and January 2009 were identified. Selected cases fit the clinical description of intrauterine HSV infection, had manifestations present at birth, and had virologic confirmation of infection. Results: This review yielded 64 cases, 3 of which were our own, of intrauterine HSV infection. Less than one-third fit the typical triad. Of the patients with cutaneous findings at birth, 24 (44%) had manifestations other than vesicles or bullae. Confirmation of HSV infection by culture of cutaneous lesions present at birth was delayed beyond 72 hours after birth in 15 patients and occurred at a median of 10 days of age. Nine of these patients had lesions at birth that were neither vesicles nor bullae, and 14 cases were confirmed by culture of new vesicles. Conclusions: More than two-thirds of reported cases do not present with the typical triad. Cutaneous findings are not limited to vesicles or bullae. A high index of suspicion and recognition of varied cutaneous manifestations is necessary to diagnose infants with intrauterine HSV infection.

Antimicrobial Stewardship in Pediatrics: How Every Pediatrician Can Be a Steward

Antimicrobial stewardship (AS) programs are effective in improving clinical outcomes associated with antimicrobial therapies while improving patient safety by reducing adverse events and development of bacterial resistance. Understanding the basic principles of AS is essential to the successful development and implementation of AS strategies. Identifying and developing strategies to address barriers and challenges to AS can facilitate the establishment of financial, administrative, and organizational support, and agreement and participation by individual prescribers. Review of published outcomes of AS demonstrates the effectiveness in reducing unnecessary antimicrobial use and adverse events such as Clostridium difficile infections. We also illustrate the need for further research and expansion of AS activities to office-based practices and communities by using novel and innovative AS strategies and by influencing regional and national policies.

Use of Type V Group B Streptococcal Conjugate Vaccine in Adults 65–85 Years Old

One-third of the cases of invasive group B streptococcal (GBS) disease now occur in adults >or=65 years old. Serotype V is most frequent among these invasive isolates. The safety and immunogenicity of type V GBS capsular polysaccharide (CPS)-tetanus toxoid (V-TT) conjugate vaccine (CV) were assessed in 32 healthy adults 65-85 years old who were randomized to receive a single intramuscular dose of V-TT CV (n=22) or licensed tetanus-diphtheria toxoid vaccine (Td) (n=10; double-masked design). V-TT CV elicited significant increases in type V CPS-specific immunoglobulin (Ig) G, IgM, and IgA serum concentrations 4, 8, 26, and 52 weeks after immunization. V-TT-induced type V CPS-specific antibodies promoted the opsonophagocytic killing of type V GBS in vitro. Both vaccines elicited similar concentrations of TT-specific IgG in 4-week postimmunization serum samples. These results suggest the potential for prevention of invasive type V GBS infections in healthy elderly adults through immunization.

Candida non-albicans versus Candida albicans fungemia in the non-neonatal pediatric population.

Background: Non-albicans Candida (NAC) species have been implicated as major pathogens in patients with hospital-acquired candidemia. Few studies have investigated the impact of NAC fungemia among pediatric patients outside of the neonatal age group. Materials/Methods: Between 2000 and 2009, we performed a retrospective case-control study in children aged 6 months to ≤18 years with blood culture proven candidemia at Texas Childrens Hospital, Houston, TX. Results: A total of 276 episodes of candidemia occurred in 226 patients. The overall incidence ranged between 0.06 and 0.3 per 1000 inpatient days. The median patient age was 50 months (range, 6 months to ≤18 years) with 55.4% males; 40.2% Hispanics; and 31.8% whites. Candida albicans (CA) was the most common (44.2%) species although, collectively, NAC was more frequently (55.8%) isolated. Among the NAC group, Candida parapsilosis was most common (23.9%) followed by Candida tropicalis (14.8%), Candida glabrata (6.5%), and Candida lusitaniae (5.4%). No difference was found between CA and NAC candidemia in terms of demographics, underlying diagnosis, risk factors, clinical features, dissemination, or 30-day mortality. Disseminated candidiasis was independently associated with the use of vasopressors (adjusted odds ratio [OR], 4.58; confidence interval [CI]: 1.03–20.5; P = 0.05), prolonged fungemia (≥3 days of persistently positive cultures) after catheter removal (OR, 3.2; CI: 1.08–9.3; P = 0.04), and neutropenia (OR, 4.06; CI: 1.2–13.2; P = 0.02), but not with NAC fungemia. Conclusions: Though CA was the single most common species, NAC species collectively have emerged as the predominant pathogens responsible for candidemia in non-neonatal patients at our institution. Risk factors, clinical features, and outcomes were not different between the 2 groups.