Emeritus Faculty-Med Ctr Line, Pediatrics - Infectious Diseases
Dr. Gutierrez' research interests include clinical studies of anti-viral therapies in infants. She also studies the epidemiology of childhood infectious diseases in California, and the epidemiology of hospital acquired infections.
The investigators hope to learn 1) if the addition of prophylaxis with vancomycin will decrease the rate of cefazolin non-susceptible SSI's, in high risk population 2) to develop better understanding of vancomycin and cefazolin pharmacokinetics in children undergoing cardiopulmonary bypass 3) to assess the barriers to vancomycin dosing peri-operatively 4) to assess side effects and risks associated with peri-operative vancomycin administration. This will allow us to improve patient care by better understanding the benefits or the risks of peri-operative vancomycin administration and potentially decrease cefazolin-resistant surgical site infections. In addition, this study gives us the opportunity to evaluate cefazolin and vancomycin pharmacokinetics on children on CPB. The investigators will take blood samples from 20 patients. In 10 patients the investigators will do Cefazolin pK analysis and in the other 10 the investigators will do pK Vancomycin analysis. For the remainder of 292 patients, only prospective chart review will be done to determine the incidence of SSI's. This data will be compared with 936 controls who received only Cefazolin pre-operatively as prophylaxis for SSI's. --------------------------------------------------------------------------------
Stanford is currently not accepting patients for this trial. For more information, please contact Kathleen Gutierrez, MD, 650-736-7642.
Cytomegalovirus (CMV) is the most common cause of congenital infection worldwide. Urine viral culture is the standard for CMV diagnosis in neonates and infants. The objectives of this study were to compare the performance of serial paired rapid shell vial cultures (SVC) and routine viral cultures (RVC), and to determine the optimal number of cultures needed to detect positive cases. From 2001 to 2011, all paired CMV SVC and RVC performed on neonates and infants less than 100 days of age were recorded. Testing episodes were defined as sets of cultures performed within 7 days of one another. A total of 1264 neonates and infants underwent 1478 testing episodes; 68 (5.4%) had at least one episode with a positive CMV culture. In episodes where CMV was detected before day 21 of life, the first specimen was positive in 100% (16/16) of cases. When testing occurred after 21 days of life, the first specimen was positive in 82.7% (43/52) of cases, requiring three cultures to reach 100% detection. The SVC was more prone to assay failure than RVC. Overall, when RVC was compared to SVC, there was 86.0% positive agreement and 99.9% negative agreement. In conclusion, three serial urine samples are necessary for detection of CMV in specimens collected between day of life 22 and 99, while one sample may be sufficient on or before day of life 21. Though SVC was more sensitive than RVC, the risk of SVC failure supports the use of multimodality testing to optimize detection.
View details for DOI 10.2350/14-01-1432-OA.1
View details for PubMedID 24617645
We conducted a retrospective, observational, population-based study to investigate the effect of staphylococcal infections on the hospitalization of children in California during 1985-2009. Hospitalized children with staphylococcal infections were identified through the California Office of Statewide Health Planning and Development discharge database. Infections were categorized as community onset, community onset health care-associated, or hospital onset. Infection incidence was calculated relative to all children and to those hospitalized in acute-care facilities. A total of 140,265 records were analyzed. Overall incidence increased from 49/100,000 population in 1985 to a peak of 83/100,000 in 2006 and dropped to 73/100,000 in 2009. Staphylococcal infections were associated with longer hospital stays and higher risk for death relative to all-cause hospitalizations of children. The number of methicillin-resistant Staphylococcus aureus infections increased, and the number of methicillin-susceptible S. aureus infections remained unchanged. Children <3 years of age, Blacks, and those without private insurance were at higher risk for hospitalization.
View details for DOI 10.3201/eid1901.111740
View details for Web of Science ID 000328172800002
Disseminated infection due to nontuberculous Mycobacterium (NTM) species is rare in pediatrics. Here we report 6 infections affecting 5 patients at a single institution in an immunocompromised population of pediatric oncology and stem cell transplant recipients. The patients presented within a 1-year period with catheter-associated bacteremia. New pulmonary nodules were noted in 4 of the 5 patients. All of the infections were due to rapidly growing NTM. Patients were successfully treated with removal of the infected catheter and combination antibiotic therapy. There are currently no consensus guidelines for treatment of NTM infections in this population, and a therapeutic approach is presented here.
View details for Web of Science ID 000268815000006
View details for PubMedID 19641470
To evaluate the impact of methicillin-resistant Staphylococcus aureus on the prevalence of S. aureus bloodstream infection among children.Retrospective analysis of demographic data, risk factors for infection, and clinical outcomes for children (age, less than 18 years) with S. aureus bacteremia hospitalized at a children's hospital during 2001-2006.We identified 164 episodes of S. aureus bacteremia among 151 children. The prevalence of bacteremia due to methicillin-susceptible S. aureus during 2001-2003 was approximately the same as that during 2004-2006 (29 and 30 cases, respectively, per 10,000 hospitalized children [hereafter, "per 10,000 hospitalizations"]), but the prevalence of bacteremia due to methicillin-resistant S. aureus increased from 4 to 11 cases, respectively, per 10,000 hospitalizations (P=.015). A total of 48% of infections involved children who had S. aureus-positive blood cultures less than 3 days after hospital admission. Seventy-four percent of these children had a preexisting comorbidity. When the prevalence of S. aureus bacteremia was stratified by race, sex, or age, neonates hospitalized at birth and Hispanic children had significantly reduced risks of infection. Children younger than 1 year of age (excluding neonates hospitalized at birth) had an increased prevalence of hospital-onset S. aureus bacteremia. There was a disproportionate increase in the risk of S. aureus bacteremia for each additional week of hospitalization among children with hospital-onset S. aureus bacteremia. Children with methicillin-resistant S. aureus bacteremia had a longer hospital stay, were transferred to another facility at a greater rate than they were discharged home, and had a greater mortality rate, compared with children with methicillin-susceptible S. aureus bacteremia.This study documents the prevalence of S. aureus bacteremia among children with a high risk for acquiring this infection, and it describes populations of children who are at higher risk for bacteremia due to either methicillin-susceptible or methicillin-resistant S. aureus. Methods to improve prevention of S. aureus bacteremia are needed for children with healthcare-associated risk factors for S. aureus bacteremia.
View details for DOI 10.1086/597521
View details for Web of Science ID 000266826600004
View details for PubMedID 19496643
We report 4 patients who developed hyperphosphatemia while receiving liposomal amphotericin B to treat an invasive fungal infection. Resolution of the hyperphosphatemia occurred after transition to amphotericin B lipid complex. This phenomenon may occur more commonly in patients with mild to moderate renal insufficiency.
View details for DOI 10.1097/INF.0b013e31815922a3
View details for Web of Science ID 000252076200019
View details for PubMedID 18162947
Cryptosporidium is an intracellular protozoa that can cause gastroenteritis in humans. In immunocompromised hosts, infection can be severe, leading to life-threatening persistent diarrhea. There is limited experience in treating this infection in solid organ transplants. Although newer drugs active against Cryptosporidium exist, they are only licensed in the USA for treatment of immunocompetent hosts. Here we describe a seven-year-old renal transplant recipient with severe cryptosporidiosis. He had a protracted course of diarrhea of up to 2 L/day. He was successfully managed with combination antimicrobial therapy including nitazoxanide, paromomycin, and azithromycin. In conjunction with this regimen, he had a reduction in immunosuppression and complete bowel rest. His stool pattern normalized in four weeks and he has had no recurrence after six months of follow up.
View details for DOI 10.1111/j.1399-3046.2006.00593.x
View details for Web of Science ID 000244147500017
View details for PubMedID 17239130
We describe a pediatric renal transplant patient with Mycobacterium bovis disease who was successfully treated using an antituberculosis regimen that included rifampin. We discuss the history of M. bovis and the diagnosis and management of M. bovis infection in renal transplant patients.
View details for DOI 10.1097/01.inf.0000219482.75490.d5
View details for Web of Science ID 000238432300020
View details for PubMedID 16732161
Bone and joint infections are a significant cause of morbidity in infants and young children. Although many principles regarding pathogenesis, diagnosis, and treatment of infection have remained constant over the years, other aspects of this important pediatric diagnosis are continuing to evolve. This article reviews current information regarding pathogenesis, epidemiology, and microbiology of pediatric bone and joint infections and the clinical presentation, diagnosis, and treatment of these infections.
View details for DOI 10.1016/j.pcl.2005.02.005
View details for Web of Science ID 000230166000007
View details for PubMedID 15925662
Because of the widespread availability of rapid viral antigen testing, many institutions never adopted a routine practice of ordering viral cultures to detect community-acquired respiratory viruses (CRVs). The ease of performing complete viral studies in our on site laboratory allowed us to assess the clinical implications of the absence of conventional culture results in previously healthy hospitalized children with CRV infections.From June 1997 through May 2000, the results of direct immunofluorescence assay (DFA) of 1069 nasopharyngeal swab (NP) specimens were compared with simultaneously inoculated conventional tube cell cultures for detection of CRVs. In addition the medical records of 140 previously healthy infants and children hospitalized for management of lower respiratory tract infections caused by culture-proved CRVs were reviewed.Viruses were isolated or detected by DFA or viral culture or both in 468 (30%) of the 1557 NP samples evaluated. The most common CRV isolated was respiratory syncytial virus (49%), followed by parainfluenza viruses (15%), influenza A viruses (14%), rhinoviruses (8%), adenoviruses (4%), enteroviruses (4%) and influenza B viruses (1%). Of the 1069 NP specimens for which both viral culture and rapid antigen testing were performed, 190 specimens were DFA-positive and culture-positive, 7 specimens were DFA-positive and culture-negative, 35 specimens were DFA-negative and culture-positive and 837 specimens were DFA-negative and culture-negative. The overall sensitivity, specificity, positive predictive value and negative predictive value of DFA were 84, 99, 96 and 96%, respectively. Of the 140 hospitalized patients with culture-proved viral cultures (89 respiratory syncytial virus, 22 influenza A, 20 parainfluenza virus and 9 adenovirus), the mean duration of hospital stay was 3.6 days, and the mean time for viral cultures to become positive was 7.7 days (P < 0.001, signed rank test). One hundred twenty (86%) viral cultures did not become positive until after the patient had been discharged from the hospital. In no case was the clinical decision regarding the patient's treatment or discharge from the hospital based on the results of viral culture.We conclude that positive viral cultures have no impact on clinical decision making and management of healthy children during hospitalization for illness attributable to community-acquired respiratory viruses.
View details for Web of Science ID 000185686400008
View details for PubMedID 14506369
Defects in IL-12 production or IL-12 responsiveness result in a vulnerability to infection with non-viral intracellular organisms, but the immunological mechanisms responsible for this susceptibility remain poorly understood. We present an immunological analysis of a patient with disseminated Salmonella enteritidis and a homozygous splice acceptor mutation in the IL-12Rbeta1-chain gene. This mutation resulted in the absence of IL-12Rbeta1 protein on PBMC and an inability of T cells to specifically bind IL-12 or produce IFN-gamma in response to either IL-12 or IL-23. The accumulation of memory (CD45R0(high)) CD4 T cells that were CCR7(high) (putative central memory cells) was normal or increased for age. Central memory CD4 T cells of the patient and age-matched controls were similar in having a low to undetectable capacity to produce IFN-gamma after polyclonal stimulation. In contrast, the patient had a substantial decrease in the number of CCR7(neg/dull) CD45R0(high) memory CD4 T cells (putative effector memory cells), and these differed from control cells in having a minimal ability to produce IFN-gamma after polyclonal stimulation. Importantly, tetanus toxoid-specific IFN-gamma production by PBMC from the patient was also significantly reduced compared with that in age-matched controls, indicating that signaling via the IL-12Rbeta1-chain is generally necessary for the in vivo accumulation of human memory CD4 T cells with Th1 function. These results are also consistent with a model in which the IL-12Rbeta1 subunit is necessary for the conversion of central memory CD4 T cells into effector memory cells.
View details for Web of Science ID 000180106600075
View details for PubMedID 12496448
The objective of this investigation was to establish the safety of high-dose (HD) acyclovir for the treatment of neonatal herpes simplex virus (HSV) disease. In addition, an estimate of therapeutic efficacy was sought, both with respect to mortality and to morbidity. Virologic efficacy of HD acyclovir was also assessed.Infants who were =28 days old and whose disease was considered to be caused by HSV were enrolled in this study. Patients with central nervous system (CNS; N = 28) or disseminated (N = 41) HSV infection were offered participation in the trial. A small number of patients with HSV disease limited to the skin, eyes, or mouth (SEM; N = 10) or whose disease was clinically consistent with HSV but who did not have virologic confirmation of infection (N = 9) also were enrolled on a compassionate basis. Only patients with virologically confirmed HSV disease were included in efficacy analyses. All enrolled patients were included in safety analyses.The study was an open-label evaluation of intravenous acyclovir at dosages higher than the 30 mg/kg/d standard dosage approved by the US Food and Drug Administration. The first 16 patients enrolled received intermediate-dose (ID) acyclovir (45 mg/kg/d), and the next 72 patients received HD acyclovir (60 mg/kg/d). Acyclovir was administered in 3 divided daily doses for 21 days. Neonates were assessed prospectively throughout treatment and at scheduled follow-up visits for the first 4 years of life. Data were compared with those of a previous National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group trial in which patients received standard-dose (SD) acyclovir for 10 days and in which identical methods (with the exception of acyclovir dosage and duration of therapy) were used.Six (21%) of 29 HD acyclovir recipients whose HSV disease remained localized to the SEM or CNS experienced neutropenia. One of the 6 had an absolute neutrophil count <500/mm(3), and 5 patients had an absolute neutrophil count (ANC) between 500/mm(3) and 1000/mm(3). In all 6 cases, the ANC recovered during continuation of acyclovir at the same dosage or after completion of acyclovir therapy, and there were no apparent adverse sequelae of the transient neutropenia. No other drug-related adverse events were reported among ID or HD recipients, and no other laboratory aberrations could be correlated specifically with antiviral therapy. The survival rate for the patients with disseminated HSV disease treated with HD acyclovir was significantly higher than for those in the previous study treated with SD acyclovir, with an odds ratio (OR) of 3.3 (95% confidence interval [CI]: 1.4-7.9). For patients with CNS disease, however, survival rates were similar for the HD and SD groups. To assess the effect of HD acyclovir on survival for the entire population with neonatal HSV disease, the Cox proportional hazards regression analysis was performed with stratification for disease category (CNS versus disseminated). In performing this analysis, differences in mortality for each disease category were weighted to allow statistical comparison of the treatment dosage groups (HD, ID, and SD). This analysis indicated that the survival rate for patients treated with HD acyclovir was statistically significantly higher than for patients treated with SD acyclovir (OR: 3.3; 95% CI: 1.5-7.3). Recipients of HD acyclovir had a borderline significant decrease in morbidity compared with SD recipients, after stratification for the extent of disease (SEM vs CNS vs disseminated) and controlling for the potential confounding factors of HSV type (HSV-1 vs. HSV-2), prematurity, and disease severity (seizures). Patients treated with HD acyclovir were 6.6 times (adjusted OR; 95% CI: 0.8-113.6) as likely to be developmentally normal at 12 months of age as patients treated with SD therapy.These data support the use of a 21-day course of HD (60 mg/kg/d) intravenous acyclovir to treat neonatal CNS and disseminated HSV disease. Throughout the course of HD acyclovir therapy, serial ANC determination should be made at least twice weekly. Decreasing the acyclovir dosage or administering granulocyte colony-stimulating factor should be considered if the ANC remains below 500/mm(3) for a prolonged period.
View details for Web of Science ID 000170211800022
View details for PubMedID 11483782
During the 2 decades in which effective antiviral therapies have been available for neonatal herpes simplex virus (HSV) disease, changes have been documented not only in the outcomes of infected infants, but also in the natural history of the disease itself. Numerous studies previously have reported that early institution of antiviral therapy is beneficial to the outcome of the disease. The objective of this study was to provide an update of neonatal HSV disease to identify means by which future improvements in the management of HSV-infected neonates can be made.Neonates enrolled in 2 studies of parenteral acyclovir for the treatment of neonatal HSV disease provided the data source. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group conducted the studies between 1981 and 1997. A total of 186 patients are summarized, all of whom were treated with acyclovir. Demographic and clinical characteristics of these patients are reported.Comparisons between patients treated in the periods between 1981-1988 and 1989-1997 according to extent of disease revealed that the mean time between the onset of disease symptoms and initiation of therapy has not changed significantly from the early 1980s to the late 1990s. Of all patients evaluated, 40% had fetal scalp monitors during the delivery process. A significant minority of patients did not have skin vesicles at the time of their presentation and did not develop them during the acute HSV disease (39% of patients with disseminated disease; 32% of patients with central nervous system [CNS] disease; and 17% of patients with skin, eye, and/or mouth disease). Among patients with CNS disease, mortality was associated with prematurity. Among patients with disseminated HSV disease treated with acyclovir at 30 mg/kg/d, mortality was associated with aspartate transaminase elevations of >/=10 times the upper limit of normal at the time of initiation of acyclovir therapy. Mortality was also associated with lethargy at initiation of antiviral therapy for patients with disseminated disease. Patients' morbidity status was associated with the extent of disease (skin, eye, and/or mouth disease vs CNS vs disseminated). For those patients with CNS disease, morbidity was also associated with seizures at initiation of antiviral therapy.Data presented in the current comparison of neonatal HSV disease over the 2 periods (1981-1988 vs 1989-1997) demonstrate that no progress has been made in decreasing the interval between onset of HSV symptoms and initiation of antiviral therapy. Additional strides in the improvement of disease outcome may occur only if the interval between onset of symptoms and initiation of therapy is shortened. The means by which this will be accomplished lie in increased consideration of neonatal HSV infections in acutely ill infants. Specific data and recommendations to facilitate this goal are contained within.
View details for Web of Science ID 000170211800021
View details for PubMedID 11483781
We report on the effectiveness of intravenous ribavirin for severe adenoviral pneumonia in a 10-month-old male following orthotopic liver transplantation. On day 20 post-transplantation, he developed high fever, marked respiratory compromise, and hypoxemia. The chest radiograph showed bilateral pulmonary infiltrates. Samples of bronchoalveolar lavage fluid grew adenovirus, serotype 1. Marked clinical and radiological improvement was noted after intravenous ribavirin therapy. A prospective clinical trial is needed to determine the efficacy of ribavirin therapy for severe adenovirus disease.
View details for Web of Science ID 000084587800011
View details for PubMedID 10613789
Infection with Nocardia poses a diagnostic challenge in patients with chronic granulomatous disease (CGD) because the signs and symptoms are often nonspecific, delay in diagnosis is common, and invasive procedures are frequently required to obtain appropriate tissue specimens. We present the first reported case of N farcinica pneumonia in an adolescent with X-linked CGD. Differentiation of N farcinica from other members of N asteroides complex is important because of its propensity for causing disseminated infection and antimicrobial resistance. Physicians caring for patients with CGD should maintain a high index of suspicion for nocardiosis, especially in those receiving chronic steroid therapy. Early diagnosis remains critical for decreased morbidity and occasional mortality.
View details for Web of Science ID 000082907300031
View details for PubMedID 10506241
Acute viral encephalitis and postinfectious encephalomyelitis affect both children and adults. Enteroviruses, HSV types 1 and 2, and arboviruses are the most common causes of encephalitis in the United States; however, the differential diagnosis is broad. History taking and physical examination can provide clues to the cause, but the diagnosis is usually established on the basis of CSF analysis, viral culture, MRI, and serologic testing, when indicated. In the future, PCR techniques may enhance rapidity of diagnosis. Until the specific cause is identified, empirical therapy should be given. Because complications can be severe, all patients with encephalitis should be monitored in a facility capable of providing supportive intensive care. Long-term follow-up is important to detect sequelae, particularly in patients with eastern equine or HSV encephalitis.
View details for Web of Science ID 000072425100017
View details for PubMedID 9519034
Many children hospitalized with serious bacterial infections are candidates for either home oral antibiotic therapy or outpatient parenteral antibiotic therapy. Outpatient antibiotic therapy offers the potential for excellent medical treatment, reduced costs, and improved quality of life for ill children. However, cost considerations must not override good medical judgment. Certain children simply are not candidates for outpatient therapy because of the seriousness of their infection, poor compliance, lack of intravenous access, or poor social situation. In addition, although the few published studies to date all show that outpatient antibiotic therapy is effective, there is further need for properly designed clinical trials to evaluate the efficacy and safety of outpatient antibiotic therapy for serious bacterial infections in children.
View details for Web of Science ID A1996VU61900007
View details for PubMedID 8938001
Comprehensive hospital discharge data completed by the California Office of Statewide Health Planning and Development was used to determine whether the proportion of infants =6 weeks of age who were hospitalized with a diagnosis of herpes simplex virus (HSV) infection changed between 1985 and 1995. During 1985, 1990, and 1995, respectively, 11.7, 11.3, and 11.4 infants per 100,000 live births had a diagnosis of HSV (P=.98). The proportion of infants 1-42 days of age who were discharged from the hospital with a diagnosis of HSV infection did not change over this time period despite a decrease in deliveries by cesarean section and an increase in the proportion of women with a diagnosis of genital HSV infection who gave birth to infants by vaginal delivery. From 1985 to 1995 there was no decrease in the rate of secondary diagnosis of genital HSV in delivering women.
View details for Web of Science ID 000081132100027
View details for PubMedID 10353880