Leonard E Weisman

Publications (24)83.2 Total impact

• Article: Appropriate antibiotic therapy improves Ureaplasma sepsis outcome in the neonatal mouse.

  Leonard E Weisman, Angela H Leeming, Lingkun Kong
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  ABSTRACT: Background:Ureaplasma causes sepsis in human neonates. Although erythromycin has been the standard treatment, it is not always effective. No published reports have evaluated Ureaplasma sepsis in a neonatal model. We hypothesized that appropriate antibiotic treatment improves Ureaplasma sepsis in a neonatal mouse model.Methods:Two ATCC strains and two clinical strains of Ureaplasma were evaluated in vitro for antibiotic minimum inhibitory concentration (MIC). In addition, FVB albino mice pups infected with Ureaplasma were randomly assigned to saline, erythromycin, or azithromycin therapy and survival, quantitative blood culture, and growth were evaluated.Results:MICs ranged from 0.125 to 62.5 µg/ml and 0.25 to 1.0 µg/ml for erythromycin and azithromycin, respectively. The infecting strain and antibiotic selected for treatment appeared to affect survival and bacteremia, but only the infecting strain affected growth. Azithromycin improved survival and bacteremia against each strain, whereas erythromycin was effective against only one of four strains.Conclusion:We have established a neonatal model of Ureaplasma sepsis and observed that treatment outcome is related to infecting strain and antibiotic treatment. We speculate that appropriate antibiotic selection and dosing are required for effective treatment of Ureaplasma sepsis in neonates, and this model could be used to further evaluate these relationships.Pediatric Research (2012); doi:10.1038/pr.2012.115.
  Pediatric Research 08/2012; · 2.70 Impact Factor
• Article: A randomized study of a monoclonal antibody (pagibaximab) to prevent staphylococcal sepsis.

  Leonard E Weisman, Helen M Thackray, Robin H Steinhorn, William F Walsh, Herbert A Lassiter, Ramasubbareddy Dhanireddy, Beverly S Brozanski, Kristine G H Palmer, Michael S Trautman, Marilyn Escobedo, H Cody Meissner, Pontthenkandath Sasidharan, Jennifer Fretz, John F Kokai-Kun, William G Kramer, Gerald W Fischer, James J Mond
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  ABSTRACT: Pagibaximab, a human chimeric monoclonal antibody developed against lipoteichoic acid, was effective against staphylococci preclinically and seemed safe and well tolerated in phase 1 studies. To evaluate the clinical activity, pharmacokinetics, safety, and tolerability of weekly pagibaximab versus placebo infusions in very low birth weight neonates. A phase 2, randomized, double-blind, placebo-controlled study was conducted at 10 NICUs. Patients with a birth weight of 700 to 1300 g and 2 to 5 days old were randomly assigned to receive 3 once-a-week pagibaximab (90 or 60 mg/kg) or placebo infusions. Blood was collected for pharmacokinetics, bacterial killing, and safety analyses. Adverse event and clinical outcome data were collected. Eighty-eight patients received pagibaximab at 90 (n = 22) or 60 (n = 20) mg/kg or placebo (n = 46). Groups were not different in demography, mortality, or morbidity. Pagibaximab demonstrated linear pharmacokinetics, a 14.5-day half-life, and nonimmunogenicity. Definite staphylococcal sepsis occurred in 0%, 20%, and 13% (P < .11) and nonstaphylococcal sepsis occurred in 0%, 10%, and 15% (P < .15) of patients in the 90 mg/kg, 60 mg/kg, and placebo groups, respectively. In all patients with staphylococcal sepsis, estimated or observed pagibaximab levels were <500 μg/mL (target level) at infection. Three once-a-week 90 or 60 mg/kg pagibaximab infusions, in high-risk neonates, seemed safe and well tolerated. No staphylococcal sepsis occurred in infants who received 90 mg/kg. Target levels were only consistently achieved after 2 to 3 doses. Dose optimization should enhance protection.
  PEDIATRICS 08/2011; 128(2):271-9. · 4.47 Impact Factor
• Article: Assessment of intrapartum antibiotic prophylaxis for the prevention of early-onset group B Streptococcal disease.

  Feng-Ying C Lin, Leonard E Weisman, Parvin Azimi, Amy E Young, Kathleen Chang, Mikhaela Cielo, Patricia Moyer, James F Troendle, Rachel Schneerson, John B Robbins
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  ABSTRACT: Most early-onset group B streptococcal (GBS) disease in recent years has occurred in newborns of prenatally GBS-negative mothers who missed intrapartum antibiotic prophylaxis (IAP). We aimed to assess the accuracy of prenatal culture in predicting GBS carriage during labor, the IAP use, and occurrence of early-onset GBS disease. We obtained vaginal-rectal swabs at labor for GBS culture from 5497 women of ≥ 32 weeks' gestation and surface cultures at birth from newborns between February 5, 2008 and February 4, 2009 at 3 hospitals in Houston, TX and Oakland, CA. Prenatal cultures were performed by a healthcare provider during routine care, and culture results were obtained from medical records. The accuracy of prenatal culture in predicting intrapartum GBS carriage was assessed by positive and negative predictive values. Mother-to-newborn transmission of GBS was assessed. Newborns were monitored for early-onset GBS disease. GBS carriage was 24.5% by prenatal and 18.8% by labor cultures. Comparing prenatal with labor GBS cultures of 4696 women, the positive predictive value was 50.5% and negative predictive value was 91.7%. IAP, administered to 93.3% of prenatally GBS-positive women, was 83.7% effective in preventing newborn's GBS colonization. Mother-to-newborn transmission of GBS occurred in 2.6% of elective cesarean deliveries. Two newborns developed early-onset GBS disease (0.36/1000 births); the prenatal GBS culture of one was negative, the other's was unknown. IAP was effective in interrupting mother-to-newborn transmission of GBS. However, approximately 10% of prenatally GBS-negative women were positive during labor and missed IAP, whereas approximately 50% of prenatally GBS-positive women were negative during labor and received IAP. These findings emphasize the need for rapid diagnostics during labor.
  The Pediatric Infectious Disease Journal 05/2011; 30(9):759-63. · 3.58 Impact Factor
• Article: Patient isolation measures for infants with candida colonization or infection for preventing or reducing transmission of candida in neonatal units.

  Mohan Pammi, Oya Eddama, Leonard E Weisman
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  ABSTRACT: Candida is a common nosocomial infection and is associated with increased healthcare costs. In neonates, candida infection is associated with high mortality and morbidity and is transmitted by direct and indirect contact. Patient isolation measures, i.e. single room isolation or cohorting, are usually recommended for infections that spread by contact. To determine the effect of patient isolation measures (single room isolation and/or cohorting) for infants with candida colonization or infection as an adjunct to routine infection control measures on the transmission of candida to other infants in the neonatal unit. Relevant trials in any language were searched in the following databases in July 2011: The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2011), MEDLINE, BIOSIS, EMBASE and CINAHL. Proceedings of the Pediatric Academic Societies (from 1987) and ongoing trials were searched. Types of studies: Cluster randomized trials (where clusters may be defined by hospital, ward, or other subunits of the hospital). Types of participants: Neonatal units caring for infants colonized or infected with Candida. Types of interventions: A policy of patient isolation measures (single room isolation or cohorting of infants with Candida colonization or infection) compared to routine isolation measures. The standard methods of the Cochrane Neonatal Review Group (CNRG) were used to identify studies and to assess the methodological quality of eligible cluster-randomized trials. Infection rates and colonization rates were to be expressed as rate ratios for each trial and if appropriate for meta-analysis, the generic inverse variance method in RevMan was to be used. No eligible trials were identified. The review found no evidence to either support or refute the use of patient isolation measures (single room isolation or cohorting) in neonates with candida colonization or infection.Despite the evidence for transmission of candida by contact and evidence of cross-infection by health care workers, no standard policy of patient isolation measures beyond routine infection control measures exists in the neonatal unit. There is an urgent need to research the role of patient isolation measures for preventing transmission of candida in the neonatal unit. Well designed trials randomizing clusters of units or hospitals to a type of patient isolation method intervention are needed.
  Cochrane database of systematic reviews (Online) 01/2011; · 5.72 Impact Factor
• Article: Respiratory syncytial virus (RSV) prevention and treatment: past, present, and future.

  Leonard E Weisman
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  ABSTRACT: Respiratory syncytial virus (RSV) is a very important pathogen worldwide. It occurs and recurs naturally throughout life. Both short and long term morbidity, and mortality are particularly significant for infants, especially those infants with underlying conditions and risk factors. Current treatment strategies for these patients (e.g Ribavirin) are limited but several new interventions (e.g. RSV604, BTA9881, ALN-RSV01) are under investigation. Several preventive agents and strategies have been developed (e.g. RSV-IGIV, palivizumab) and others are in the pipeline (e.g. motavizumab) and under development (e,g, Medi-557). In this article, we review the RSV clinical condition with a focus on the highest risk populations. In addition we review prevention and treatment strategies of the past, present and future for these high-risk patients. This review should provide a single valuable source of information to clinicians and investigators.
  Cardiovascular & hematological agents in medicinal chemistry 08/2009; 7(3):223-33.
• Article: Motavizumab, a second-generation humanized mAb for the prevention of respiratory syncytial virus infection in high-risk populations.

  Leonard E Weisman
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  ABSTRACT: Evolved from palivizumab, motavizumab is a second-generation humanized mAb that is in development by MedImmune for the prevention of respiratory syncytial virus (RSV) infection in high-risk populations; the drug is also under investigation for the same indication by Abbott Laboratories. Motavizumab targets a highly conserved epitope in the A antigenic site of the RSV fusion (F) protein, which is important in the invasion of RSV from cell to cell. Motavizumab, which differs from palivizumab by just 13 amino acids, has exhibited a 70-fold enhancement in binding to the RSV F protein compared with the first-generation mAb, with an 11-fold faster association rate and 6-fold slower disassociation rate. Motavizumab was approximately 20-fold more potent than palivizumab in vitro, and was more effective at lower doses in vivo. In phase III clinical trials, motavizumab was non-inferior [corrected] to palivizumab in reducing the incidence [corrected] of RSV-related hospitalizations and was superior to palivizumab in reducing the incidence [corrected] of RSV-related medically attended [corrected] outpatient visits for lower respiratory tract infections in high-risk infants. In terms of safety, motavizumab has been demonstrated to be comparable with palivizumab. Until an effective prophylactic vaccine is developed, motavizumab could potentially become the first-line preventive agent against RSV disease in specific high-risk patients.
  Current opinion in molecular therapeutics 05/2009; 11(2):208-18. · 3.68 Impact Factor
• Article: Phase 1/2 double-blind, placebo-controlled, dose escalation, safety, and pharmacokinetic study of pagibaximab (BSYX-A110), an antistaphylococcal monoclonal antibody for the prevention of staphylococcal bloodstream infections, in very-low-birth-weight neonates.

  Leonard E Weisman, Helen M Thackray, Joseph A Garcia-Prats, Mirjana Nesin, Joseph H Schneider, Jennifer Fretz, John F Kokai-Kun, James J Mond, William G Kramer, Gerald W Fischer
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  ABSTRACT: Staphylococcal sepsis is a major cause of morbidity and mortality in very-low-birth-weight (VLBW) infants. A human chimeric monoclonal antibody, pagibaximab, was developed against staphylococcal lipoteichoic acid. We evaluated the safety, tolerability, and pharmacokinetics of pagibaximab in VLBW neonates. A phase 1/2, randomized, double-blind, placebo-controlled, dose escalation study was conducted in VLBW infants (700 to 1,300 g) 3 to 7 days old. Patients received two doses 14 days apart of intravenous pagibaximab (10, 30, 60, or 90 mg/kg of body weight) or placebo in a 2:1 ratio. Blood and urine samples were obtained pre- and postinfusion for analysis of safety and pharmacokinetics, and data on adverse events were gathered. Staphylococcal organisms causing sepsis were collected and evaluated. Fifty-three patients received at least one dose of pagibaximab or placebo. The average gestational age was 27.6 weeks; the average birth weight was 1,003 g. All serious adverse events were deemed unrelated or probably not drug related. Morbidity and mortality were similar across treatment groups. No evidence of immunogenicity of pagibaximab was detected. Pagibaximab pharmacokinetics was linear. The mean clearance (CL), volume of distribution, and elimination half-life of pagibaximab were independent of dose. The serum half-life was 20.5 +/- 6.8 days. Pagibaximab enhanced serum opsonophagocytic activity. All staphylococci causing sepsis were opsonizable by pagibaximab. Two infusions of pagibaximab, administered 2 weeks apart to high-risk neonates appeared safe and tolerable, and pharmacokinetics were linear. Evaluation of more frequent doses, at the highest doses tested, in neonates at high-risk of staphylococcal sepsis, is warranted.
  Antimicrobial Agents and Chemotherapy 05/2009; 53(7):2879-86. · 4.84 Impact Factor
• Article: Phannacokinetics of Intravenous Immunoglobulin in Neonates

  Leonard E. Weisman, Gerald W Fischer, Philip Marinelli, Val G. Hemming, John R. Pierce, Stephen M. Golden, Carl C. Peck
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  ABSTRACT: Intravenous immunoglobulin (IVIG) may be a therapeutic adjunct to antibiotic treatment of neonatal infections. We examined the pharmacokinetics and safety of IVIG in human neonates. Thirty neonates with suspected sepsis were randomly assigned either to a treatment (receiving either 250, 500, or 1,000 mg/kg of IVIG plus antibiotics) or control (antibiotics alone) group. The 500 mg/kg dose produced a rise in total IgG for >8 and in group B streptococcus (GBS) type-specific IgG for > 4–14 days. The type-specific antibody elevation varied with the amount of pathogen-specific antibody and dose of IVIG. Pharmacokinetic analysis suggests a Vdss of 42ml/kg, Cl of 3.0ml/kg/day, a biphasic elimination curve, and a terminal elimination half-life of 24.2 days. No toxicity was observed. These data may be valuable in determining optimal dosing schedules for IVIG in treating or preventing neonatal infections.
  Vox Sanguinis 03/2009; 57(4):243 - 248. · 2.86 Impact Factor
• Article: Population structure of invasive and colonizing strains of Streptococcus agalactiae from neonates of six U.S. Academic Centers from 1995 to 1999.

  John F Bohnsack, April Whiting, Marcelo Gottschalk, Diane Marie Dunn, Robert Weiss, Parvin H Azimi, Joseph B Philips, Leonard E Weisman, George G Rhoads, Feng-Ying C Lin
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  ABSTRACT: The purpose of this study was to describe the population structure of group B streptococci (GBS) isolated from infected and colonized neonates during a prospective active-surveillance study of early-onset disease in six centers in the United States from July 1995 to June 1999 and to examine its relationship to bovine strains of GBS. The phylogenetic lineage of each GBS isolate was determined by multilocus sequence typing, and isolates were clustered into clonal complexes (CCs) using the eBURST software program. A total of 899 neonatal GBS isolates were studied, of which 129 were associated with invasive disease. Serotype Ia, Ib, and V isolates were highly clonal, with 92% to 96% of serotype Ia, Ib, and V isolates being confined to single clonal clusters. In contrast, serotype II and III isolates were each comprised of two major clones, with 39% of serotype II and 41% of serotype III isolates in CC 17 and 41% of serotype II and 54% of serotype III isolates in CC 19. Further analysis demonstrates that the CC 17 serotype II and III GBS are closely related to a previously described "ancestral" lineage of bovine GBS. While 120 (93%) of invasive GBS were confined to the same lineages that colonized neonates, 9 (7%) of the invasive GBS isolates were from rare lineages that comprised only 2.7% of colonizing lineages. These results are consistent with those for other geographic regions that demonstrate the highly clonal nature of GBS infecting and colonizing human neonates.
  Journal of clinical microbiology 05/2008; 46(4):1285-91. · 4.16 Impact Factor
• Article: Lysostaphin in treatment of neonatal Staphylococcus aureus infection.

  Okunola Oluola, Lingkun Kong, Mindy Fein, Leonard E Weisman
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  ABSTRACT: This study describes lysostaphin's effect against methicillin-sensitive Staphylococcus aureus in suckling rats. Standard techniques determined minimal inhibitory and bactericidal concentrations, pharmacokinetics, and efficacy. The numbers of surviving rats after vancomycin, oxacillin, and lysostaphin treatment were comparable and were different from that of controls (P < 0.00001). Lysostaphin appears effective in the treatment of neonatal S. aureus infection.
  Antimicrobial Agents and Chemotherapy 07/2007; 51(6):2198-200. · 4.84 Impact Factor
• Article: Neonatal coinfection model of coagulase-negative Staphylococcus (Staphylococcus epidermidis) and Candida albicans: fluconazole prophylaxis enhances survival and growth.

  Mohan Pammi Venkatesh, Don Pham, Mindy Fein, Lingkun Kong, Leonard E Weisman
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  ABSTRACT: Coagulase-negative staphylococci (CoNS) and Candida are among the most common causes of single infections and coinfections in neonates after 72 h of age. In neonates, coinfection increases the rate of mortality threefold and results in significantly greater morbidity compared to those that result from single infections. In an effort to better understand this phenomenon, we developed the first neonatal animal model of coinfection (with CoNS and Candida) and evaluated its effects on mortality and morbidity and the impact of antifungal prophylaxis with fluconazole. Neonatal Wistar rats were infected with Candida albicans and/or Staphylococcus epidermidis with doses of 2x10(8) and 2x10(6) CFU subcutaneously in different combinations and were monitored for mortality, weight gain, and bacteremia. The in vitro sensitivity of C. albicans to fluconazole was evaluated and the MIC was determined. A subset of rats in these experiments received fluconazole at 10 mg/kg of body weight/dose intraperitoneally starting 24 h before infection for 4 days, and the serum trough levels of fluconazole were measured. Coinfection in the suckling rat significantly increased the rate of mortality compared to that after infection with a single species (P<0.001) and resulted in deaths even at sublethal doses. Coinfection also impaired weight gain significantly in severely infected pups compared to that achieved after infection with a single species (P<0.001). Fluconazole prophylaxis significantly reduced mortality by 30% in the Candida group and 36% in the coinfection group and improved weight gain in this neonatal model of coinfection (P<0.001). We developed a neonatal model of coinfection with Candida and CoNS, observed significantly greater mortality and morbidity with coinfection, and found that fluconazole prophylaxis significantly reduced the rates of both mortality and morbidity. Further research on neonatal coinfection is urgently needed to improve clinical outcomes.
  Antimicrobial Agents and Chemotherapy 04/2007; 51(4):1240-5. · 4.84 Impact Factor
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  Article: Coagulase-negative staphylococcal infections in the neonate and child: an update.

  Mohan P Venkatesh, Frank Placencia, Leonard E Weisman
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  ABSTRACT: Coagulase-negative staphylococcus (CONS) infection is the most common bloodstream infection treated in neonatal and pediatric intensive care units and significantly impacts patient mortality and morbidity. Staphylococcus epidermidis is the most common CONS species isolated clinically and investigated for its pathogenicity and virulence. Difficulties exist in the differentiation of CONS infection from culture contamination in clinical specimens, as CONS is a common skin commensal. Most CONS isolates have the mecA gene and exhibit beta-lactam resistance. The glycopeptide antibiotics, such as vancomycin, are the mainstay in therapy, although resistance has been reported. Arbekacin, linezolid, and streptogramins are newer antibiotics being evaluated as alternatives to glycopeptides. Monoclonal and polyclonal antibodies have been developed against the cell-wall components of staphylococcus and may hold promise for immune prophylaxis and treatment of CONS infection.
  Seminars in Pediatric Infections Diseases 08/2006; 17(3):120-7.
• Article: Prevention and treatment of respiratory syncytial virus infection in infants: an update.

  Mohan Pammi Venkatesh, Leonard E Weisman
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  ABSTRACT: Respiratory syncytial virus (RSV) is a serious pathogen causing significant mortality and morbidity, especially in premature infants and infants with chronic lung disease or significant congenital heart disease. Therapy for RSV infection is essentially supportive, although several new compounds are under investigation. Therefore, immunoprophylaxis to prevent severe RSV disease in high-risk infants assumes great significance. Palivizumab, a humanized monoclonal antibody to RSV, significantly reduces hospitalization in the first 6 months in premature infants born at less than 35 weeks, infants less than 24 months of age with chronic lung disease and requiring treatment in the last 6 months, and in children 24 months or younger with hemodynamically significant heart disease. A new ultrapotent anti-RSV antibody (MEDI-524) appears to be more effective in animals than palivizumab and is undergoing clinical evaluation. There has been considerable progress in the development of vaccines; namely subunit, live attenuated, genetically recombinant virus and polypeptide vaccines. Plasmid DNA vaccines coding for parts of the F and G surface glycoproteins and vaccinia vector vaccines are also being evaluated. Maternal immunization has the potential to prevent RSV disease in early infancy. RSV prophylaxis has seen tremendous progress in the last decade.
  Expert Review of Vaccines 05/2006; 5(2):261-8. · 4.25 Impact Factor
• Article: Phylogenetic lineages of invasive and colonizing strains of serotype III group B Streptococci from neonates: a multicenter prospective study.

  Feng-Ying C Lin, April Whiting, Elisabeth Adderson, Shinji Takahashi, Diane Marie Dunn, Robert Weiss, Parvin H Azimi, Joseph B Philips, Leonard E Weisman, Joan Regan, Penny Clark, George G Rhoads, Carl E Frasch, James Troendle, Patricia Moyer, John F Bohnsack
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  ABSTRACT: This study compares the phylogenetic lineages of invasive serotype III group B streptococci (GBS) to those of colonizing strains in order to determine lineages associated with invasive disease. Isolates from 29 infants with early-onset disease (EOD) and from 196 colonized infants, collected in a prospective, multicenter study, were assigned a sequence type (ST) by multilocus sequence typing. Overall, 54.5% of the isolates were in the ST-19 complex, and 40.4% were in the ST-17 complex. Invasive strains were more likely to be in the ST-17 complex than were colonizing strains (59% versus 38%, P = 0.03). After we adjusted for potential confounders, the ST-17 complex was more likely to be associated with EOD than were other lineages (odds ratio = 2.51, 95% confidence interval = 1.02 to 6.20). These data support the hypothesis that ST-17 complex GBS are more virulent than other serotype III GBS.
  Journal of Clinical Microbiology 05/2006; 44(4):1257-61. · 4.15 Impact Factor
• Article: Level of maternal IgG anti-group B streptococcus type III antibody correlated with protection of neonates against early-onset disease caused by this pathogen.

  Feng-Ying C Lin, Leonard E Weisman, Parvin H Azimi, Joseph B Philips, Penny Clark, Joan Regan, George G Rhoads, Carl E Frasch, Barry M Gray, James Troendle, Ruth A Brenner, Patricia Moyer, John D Clemens
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  ABSTRACT: The present study estimates the level of maternal immunoglobulin (Ig) G anti-group B streptococcus (GBS) type III required to protect neonates against early-onset disease (EOD) caused by this pathogen. Levels of maternal serum IgG anti-GBS type III, measured by enzyme-linked immunosorbent assay, in 26 case patients (neonates with EOD caused by GBS type III) and 143 matched control subjects (neonates colonized by GBS type III who did not develop EOD) of > or = 34 weeks gestation were compared. The probability of EOD decreased with increasing levels of maternal IgG anti-GBS type III (P = .01). Neonates whose mothers had > or = 10 microg/mL IgG anti-GBS type III had a 91% lower risk for EOD, compared with those whose mothers had levels of < 2 microg/mL. A vaccine that induces IgG anti-GBS type III levels of > or = 10 microg/mL in mothers can be predicted to offer a significant degree of protection against EOD caused by this pathogen.
  The Journal of Infectious Diseases 09/2004; 190(5):928-34. · 6.41 Impact Factor
• Article: Coagulase-negative staphylococcal disease: emerging therapies for the neonatal and pediatric patient.

  Leonard E Weisman
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  ABSTRACT: Due to the high frequency, significant clinical impact, and cost of coagulase-negative staphylococcal infections, a great deal of effort continues in the investigation of the epidemiology, prevention, and treatment of coagulase-negative staphylococcal infection in the neonate and infant. Pediatric oncology and burn patients appear to be high-risk groups for coagulase-negative staphylococcal infections. Coagulase-negative staphylococcus appears to be the major pathogen world-wide, and associated with significant morbidity and mortality in neonatal intensive care units, in pediatric intensive care units, and following ophthalmologic surgery. A screened human polyclonal antibody and a humanized chimeric monoclonal antibody are both under investigation (in phase II-III clinical trials) for prevention of coagulase-negative staphylococcal infections in high-risk neonates. Resistance of coagulase-negative staphylococcus to antibiotics appears to be increasing. Should neonates with sepsis and central catheters have their catheters removed immediately or only when the infection is persistent? Arbekacin and linezolid are two new antibiotics that appear to be effective in the treatment of coagulase-negative staphylococcal infections, but their precise role has not yet been identified. This article summarizes the significant clinical reports about coagulase-negative staphylococcal infections since December 2002.
  Current Opinion in Infectious Diseases 07/2004; 17(3):237-41. · 4.93 Impact Factor
• Article: Dexamethasone effects on group B streptococcal infection in newborn rats.

  Thuy-Van P Tran, Leonard E Weisman
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  ABSTRACT: We previously published that human neutrophil-mediated bacterial killing of group B Streptococcus (GBS) in vitro was dependent on the timing and concentration of dexamethasone exposure. Dexamethasone treatment would affect neutrophil mediated killing of GBS in an animal model. Wistar rat pups were randomly allocated to receive placebo or dexamethasone before, early or late after GBS infection. Suckling rats were infected with 104 or 105 colony-forming units of GBS or nothing. Pups were followed for survival, quantitative bacteremia, growth and neutrophil-mediated bacterial killing. Neutrophils for bacterial killing were obtained via cardiac puncture before infection. Statistics included chi square for survival, Mann-Whitney U test for bacteremia, analysis of variance for growth and paired Student's t test for bacterial killing analyses. Dexamethasone treatment before invasive GBS infection decreases quantitative bacteremia, improves survival and improves neonatal neutrophil-mediated bacterial killing in suckling rats, whereas dexamethasone treatment after infection increases bacteremia and decreases survival. Regardless of timing of dexamethasone treatment, before or after invasive GBS infection, growth was significantly impaired in all suckling rats receiving dexamethasone compared with controls. Treatment with dexamethasone before invasive GBS infection improves survival and decreases bacteremia in suckling rats; this appears in part to be mediated by improved neonatal neutrophil-mediated bacterial killing. We speculate that this improvement in outcome may be a result of improved number or function of neutrophil cell surface receptors.
  The Pediatric Infectious Disease Journal 02/2004; 23(1):47-52. · 3.58 Impact Factor
• Article: Prematurity is the major risk factor for late-onset group B streptococcus disease.

  Feng-Ying C Lin, Leonard E Weisman, James Troendle, Karen Adams
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  ABSTRACT: A case-control study was conducted in the greater Houston area to determine risk factors for late-onset group B streptococcus (GBS) disease (onset of disease or first positive culture between 7 and 180 days after birth). Characteristics of 122 case patients diagnosed during 1995-2000 were compared with control subjects matched for birth hospital and date of birth. Half the case patients were preterm infants, 84% of whom were born at <34 weeks of gestation. The risk for late-onset GBS disease increased by a factor of 1.34 (95% confidence interval [CI], 1.15-1.56) for each week of decreasing gestation, by 3.70 (95% CI, 1.35-10.1) for infants of black mothers, and by 4.15 (95% CI, 1.27-13.60) for infants of mothers with a positive GBS screening. These risk factors are similar to that of early-onset GBS disease. However, prematurity is the major risk factor for late-onset GBS disease.
  The Journal of Infectious Diseases 08/2003; 188(2):267-71. · 6.41 Impact Factor
• Article: Necrotizing enterocolitis and gastrointestinal complications after indomethacin therapy and surgical ligation in premature infants with patent ductus arteriosus.

  Donough J O'Donovan, Arlina Baetiong, Karen Adams, Ann Chen, E O'Brian Smith, James M Adams, Leonard E Weisman
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  ABSTRACT: Indomethacin is the most frequently used pharmacological agent for closure of a patent ductus arteriosus (PDA) in premature infants. However, reports of complications, particularly, necrotizing enterocolitis (NEC) and isolated gastrointestinal perforation have generated concerns about the use of this medication. A retrospective study to compare the incidence of NEC, NEC-related gastrointestinal complications and isolated gastrointestinal perforation among premature infants treated for a PDA with either, indomethacin alone (I), surgical ligation alone (L), or indomethacin followed by surgical ligation (I-L). The medical records of 224 infants that underwent treatment, either pharmacological or surgical, for a PDA, confirmed by echocardiography, over a 4-year period (1995 to 1998) were analyzed. Treatment history and gastrointestinal complications were reviewed. Of the 224 infants, 108 (48.2%) were treated with I, 50 (22.3%) by L, 66 (29.5%) with I-L. The clinical characteristics of the three treatment groups were similar and no differences in the incidence of NEC were observed between groups. NEC occurred in 14 (13%) of the I group, seven (14%) of the L group, and eight (12%) of the I-L group. The rate of NEC related gastrointestinal complications and isolated gastrointestinal perforation were also similar among groups. In this large retrospective study, indomethacin treatment for a significant PDA in premature infants was not associated with a greater risk for NEC or NEC-related gastrointestinal complications than surgical ligation.
  Journal of Perinatology 07/2003; 23(4):286-90. · 1.80 Impact Factor
• Article: Populations at risk for developing respiratory syncytial virus and risk factors for respiratory syncytial virus severity: infants with predisposing conditions.

  Leonard E Weisman
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  ABSTRACT: According to National Vital Statistics Reports, premature infants (< 36 weeks gestation) account for approximately 7.4% of all births. During the 8 years from 1989 to 1997, multiple births steadily increased across all categories from twin to quintuplet and higher orders. During that same period low birth weight (< 2500 g) births increased almost 12%, and very low birth weight (< 1500 g) births increased approximately 20%.Attendant to these national trends in multiple and preterm births, overall gestation-specific survival rates have improved substantially. This improved outcome can be attributed in large measure to advances in neonatal care and technology. Despite the encouraging statistics on survival, infants born prematurely, at low or very low birth weights and/or with chronic conditions that predispose to lower respiratory tract illness, continue to incur serious risk of long term morbidity and the consumption of inpatient hospital services. In a recent 2-year study of US children, low and very low birth weights were found to be independent risk factors for bronchiolitis-associated mortality. In the past 14 years what defines bronchopulmonary dysplasia (BPD)/chronic lung disease (CLD) has shifted away from clinical, radiographic and pathologic findings in the preterm infant toward the pathophysiology of arrested lung development and the need for supportive care beyond 36 weeks corrected gestational age. The incidence of BPD/CLD ranges from 14 to 43%, with higher rates observed among infants of lower gestational age and birth weight. The health care team approach to the management of BPD directs its efforts toward minimizing pulmonary vascular resistance, alleviating airway obstruction and improving short term lung mechanics. Measures to prevent BPD/CLD attempt to forestall both acute and chronic lung function abnormalities. To that end researchers have investigated the early use of continuous positive airway pressure, vitamin supplementation and recombinant human copper/zinc superoxide dismutase. Despite significant gains in the survival of infants born at lower gestational ages, prematurity, low birth weight and/or underlying chronic pulmonary disease put the pediatric patient at risk for increased frequency and severity of respiratory syncytial virus lower respiratory tract illness and the potential for its long term sequelae.
  The Pediatric Infectious Disease Journal 02/2003; 22(2 Suppl):S33-7; discussion S37-9. · 3.58 Impact Factor