Association between otitis media infection and failed hearing screenings in children.

This study aims to assess prospectively whether there is an association between frequencies of upper respiratory tract infections (URTI) or asthma in early childhood and failed otoacoustic emission (OAE) screenings later in life. There are no clear recommendations for hearing testing following acute otitis media (AOM) infection. This is a retrospective, practice based chart review. Participants from a primary care setting were 517 pre-adolescent and adolescent children (49.9% female) (ages 10-21; mean, 15 y/o), who had presented with at least one specific bacterial URTI (AOM, Group A Streptococcus (GAS) tonsillitis, or Influenza) during childhood. Hearing testing was recorded incidentally at all subsequent routine health care maintenance visits (OAE hearing screen). Simple linear regression analyses were performed using R (v3.4.4). We found that number of episodes of AOM infections strongly correlated with number of failed OAE screenings later in life (F = 76.37; P = <0.001; R2 = 0.1279), while GAS (F = 1.859; P = 0.1733; R2 = 0.0016) or Influenza infection (F = 2.624; P = 0.1059; R2 = 0.0031) were not associated with failed OAE screening. Correlation between number of AOM infections and number of failed OAE screenings was not strengthened by presence of asthma. This study found evidence of an association between childhood history of AOM and failed OAE screenings in adolescence. Since this population may be at a higher risk for developing permanent or fluctuating hearing losses, further studies to clarify indications and timing of standard audiological testing among these children should be considered.

In Vitro Activity of Omadacycline against Chlamydia pneumoniae.

The in vitro activities of omadacycline, azithromycin, doxycycline, moxifloxacin, and levofloxacin were tested against 15 isolates of Chlamydia pneumoniae The minimum inhibitory concentration at which 90% of the isolates of C. pneumoniae were inhibited by omadacycline was 0.25 µg/ml (range, 0.03 to 0.5 µg/ml).

Aminomethyl Spectinomycins as Therapeutics for Drug-Resistant Gonorrhea and Chlamydia Coinfections.

Bacterial sexually transmitted infections are widespread and common, with Neisseria gonorrhoeae (gonorrhea) and Chlamydia trachomatis (chlamydia) being the two most frequent causes. If left untreated, both infections can cause pelvic inflammatory disease, infertility, ectopic pregnancy, and other sequelae. The recommended treatment for gonorrhea is ceftriaxone plus azithromycin (to empirically treat chlamydial coinfections). Antibiotic resistance to all existing therapies has developed in gonorrheal infections. The need for new antibiotics is great, but the pipeline for new drugs is alarmingly small. The aminomethyl spectinomycins, a new class of semisynthetic analogs of the antibiotic spectinomycin, were developed on the basis of a computational analysis of the spectinomycin binding site of the bacterial 30S ribosome and structure-guided synthesis. The compounds display particular potency against common respiratory tract pathogens as well as the sexually transmitted pathogens that cause gonorrhea and chlamydia. Here, we demonstrate the in vitro potencies of several compounds of this class against both bacterial species; the compounds displayed increased potencies against N. gonorrhoeae compared to that of spectinomycin and, significantly, demonstrated activity against C. trachomatis that is not observed with spectinomycin. Efficacies of the compounds were compared to those of spectinomycin and gentamicin in a murine model of infection caused by ceftriaxone/azithromycin-resistant N. gonorrhoeae; the aminomethyl spectinomycins significantly reduced the colonization load and were as potent as the comparator compounds. In summary, data produced by this study support aminomethyl spectinomycins as a promising replacement for spectinomycin and antibiotics such as ceftriaxone for treating drug-resistant gonorrhea, with the added benefit of treating chlamydial coinfections.

Evaluation of clinical outcome in children and adolescents receiving vancomycin for invasive infections due to methicillin-resistant Staphylococcus aureus: impact of increasing vancomycin MICs.

BACKGROUND: Vancomycin is the preferred drug for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in children. In adults, treatment failure with vancomycin has been associated with an area under the curve/24 hrs /MIC (AUC24/MIC) ratio of ≤400 and high minimum inhibitory concentrations (MIC ≥1.0 mg/L). Vancomycin dosing information to ensure optimal AUC24/MIC in the pediatric population remains limited. METHODS: A retrospective chart review from August 2008 to 2011 and a prospective study from September 2011 to October 2013 was conducted on all pediatric patients at two hospitals in Brooklyn, NY with positive cultures for MRSA who received vancomycin. Treatment failure was defined as persistent positive cultures (≥5 days) or persistence of clinical symptoms. Vancomycin AUC24/MICs were calculated. RESULTS: Twenty-three children with MRSA infection, 0-18 years of age, were identified; 18 of 23 (78.3%) were community acquired. MICs of 91% of the isolates were ≥1.5 µg/mL and 9 had MICs of 2 µg/mL. Treatment failure was seen in 12 (52%) patients with MICs of 1.5 µg/mL and above. Vancomycin trough levels >15 µg/mL and AUC24/MIC >400 were achieved in only 18% and 0% of patients, respectively. CONCLUSIONS: High treatment failure rates with vancomycin was associated with MIC ≥1.5 µg/mL. Current recommended vancomycin dosing in children did not achieve a trough concentration of >15 µg/mL in majority of the patients and none achieved an AUC24/MIC>400.

Seroprevalence of Chlamydia trachomatis in Inner-City Children and Adolescents-Implications for Vaccine Development.

BACKGROUND: Prevention of Chlamydia trachomatis infection is an ideal application for a vaccine program, which should optimally be administered before sexual debut. However, there are limited epidemiologic studies of C. trachomatis infection in an unselected pediatric population since routine screening and treatment of pregnant women was implemented in the United States in 1993. METHODS: Anonymized serum samples were obtained from children younger than 21 years in 2 medical centers in Brooklyn, New York, from 2013 to 2015. Anti-C. trachomatis IgG antibody was determined by a validated enzyme immunoassay. Infants younger than 1 year were excluded from the final analysis due to interference of maternal antibody. RESULTS: One thousand two sera were included in the final analysis. Fifty-seven percent were females. No antibody was detected at younger than 11 years. Anti-C. trachomatis IgG antibody was detected in 11.4% and 5.6% of female and male subjects, respectively, older than 11 years (P = 0.0027), and seropositivity increased with age. There was no significant difference in the distribution of age at infection between the centers (P = 0.432), but a difference was detected between genders (P = 0.012) with a higher percentage of female subjects testing positive. CONCLUSIONS: Antibody was first detected at 11 years of age, likely coinciding with sexual debut. The prevalence of antibody was higher and appeared earlier in females, mirroring national surveillance trends based on nucleic acid amplification testing. The delay in male antibody detection may be due to biological or behavioral differences between genders. These data are critical in informing potential C. trachomatis vaccine strategies.

Treatment of Chlamydial infections: 2014 update.

INTRODUCTION: Chlamydiae are obligate intracellular bacterial pathogens whose entry into mucosal epithelial cells is required for intracellular survival and subsequent growth. The life cycle of Chlamydia spp. and the ability to cause persistent, often subclinical infection, has major ramifications for diagnosis and treatment of Chlamydia trachomatis and C. pneumoniae infections in humans. AREAS COVERED: This paper reviews the current literature on the antimicrobial susceptibilities and treatment of genital infections due to C. trachomatis and respiratory infections due to C. pneumoniae published since 2011. EXPERT OPINION: Chlamydiae are susceptible to antibiotics that interfere with DNA and protein synthesis, including tetracyclines, macrolides and quinolones, which are the compounds that have been most extensively studied and used for treatment of human infection. Since our original review was published in 2011, there have been some major advances in diagnostic tests for C. trachomatis and the introduction of the first FDA-approved test for the detection of C. pneumoniae in respiratory samples. However, the options for treating chlamydial infections have largely remained the same. There are a small number of new drugs currently in preclinical development and early clinical trials that may have a role in the treatment of chlamydial infections.

In vitro activity of AZD0914, a novel DNA gyrase inhibitor, against Chlamydia trachomatis and Chlamydia pneumoniae.

The in vitro activities of AZD0914, levofloxacin, azithromycin, and doxycycline against 10 isolates each of Chlamydia trachomatis and Chlamydia pneumoniae were tested. For AZD0914, the MIC90s for C. trachomatis and C. pneumoniae were 0.25 µg/ml (range, 0.06 to 0.5 µg/ml) and 1 µg/ml (range, 0.25 to 1 µg/ml), respectively, and the minimal bactericidal concentrations at which 90% of the isolates were killed (MBC90s) were 0.5 µg/ml for C. trachomatis (range, 0.125 to 1 µg/ml) and 2 µg/ml for C. pneumoniae (range, 0.5 to 2 µg/ml).

In vitro activity of nemonoxacin, a novel nonfluorinated quinolone antibiotic, against Chlamydia trachomatis and Chlamydia pneumoniae.

The in vitro activities of nemonoxacin, levofloxacin, azithromycin, and doxycycline were tested against 10 isolates each of Chlamydia trachomatis and Chlamydia pneumoniae. The MICs at which 90% of the isolates of both C. trachomatis and C. pneumoniae were inhibited (MIC90s) were 0.06 µg/ml (range, 0.03 to 0.13 µg/ml). The minimal bactericidal concentrations at which 90% of the isolates were killed by nemonoxacin (MBC90s) were 0.06 µg/ml for C. trachomatis (range, 0.03 to 0.125 µg/ml) and 0.25 for C. pneumoniae (range, 0.015 to 0.5 µg/ml).

Doxycycline suppresses Chlamydia pneumoniae-mediated increases in ongoing immunoglobulin E and interleukin-4 responses by peripheral blood mononuclear cells of patients with allergic asthma.

OBJECTIVES: Chlamydia pneumoniae, an obligate intracellular bacterium, has been associated with asthma and the induction of immunoglobulin E (IgE) responses. Whereas tetracyclines have anti-chlamydial activity, their effect on human IgE responses to C. pneumoniae has not been studied. METHODS: Peripheral blood mononuclear cells (PBMCs) from serum IgE+ allergic asthmatic subjects (n = 11) and healthy controls (n = 12) were infected with C. pneumoniae and cultured for 12 days with or without doxycycline (0.01-1.0 mg/L). IgE, interferon (IFN)-γ and interleukin (IL)-4 levels in supernatants were determined on days 1-12 post-infection, and C. pneumoniae DNA copy numbers in PBMC culture were measured on day 2 (quantitative PCR). RESULTS: C. pneumoniae-infected PBMCs from allergic asthmatic individuals had increased levels of IgE in supernatants compared with uninfected PBMCs (520% on day 10 post-infection, P = 0.008). IgE levels in PBMC cultures from controls were undetectable (<0.3 ng/mL). Increases in C. pneumoniae-induced IgE in asthmatics correlated with those of C. pneumoniae-induced IL-4 (r = 0.98; P < 0.001), but not with IFN-γ. The addition of doxycycline (1.0 mg/L) to the culture strongly suppressed the production of IgE (>70%, P = 0.04) and IL-4 (75%, P = 0.018), but not IFN-γ. The suppressive effect on IL-4 production remained significant even at concentrations of doxycycline that were subinhibitory (0.01 mg/L) for C. pneumoniae. In both asthmatic participants and controls, no significant effect of doxycycline on DNA copy numbers of C. pneumoniae was observed. CONCLUSIONS: Doxycycline suppressed the C. pneumoniae-induced production of IgE and IL-4, but not IFN-γ, in PBMCs from IgE+ allergic asthmatic subjects. These findings resulted from the immunomodulatory anti-allergic properties of tetracyclines.

Asthmatic children have increased specific anti-Mycoplasma pneumoniae IgM but not IgG or IgE-values independent of history of respiratory tract infection.

BACKGROUND: Bronchial asthma is exacerbated by Mycoplasma pneumoniae-induced upper respiratory tract infections (URTIs) in children. Specific IgM and IgG isotypes are involved in the immune response to M. pneumoniae, but little is known about the role of specific IgE antibodies against M. pneumoniae in asthma. OBJECTIVE: To investigate the role of IgM-, IgG- and IgE-specific antibody responses to M. pneumoniae in children with persistent asthma in relationship to history of URTI within the past 6 months. METHODS: Total or specific anti-M. pneumoniae IgM, IgG and IgE antibody responses were studied in stable asthmatic pediatric patients (M. pneumoniae positive and negative) without current exacerbation and nonasthmatic controls (N = 23 and 13, respectively) (UniCAP total IgE Fluoroenzymeimmunoassay, enzyme-linked immunosorbent assay). RESULTS: Values of specific IgM correlated with specific IgG (Spearman correlation, rho = 0.61, P < 0.0001) but not with specific IgE anti-M. pneumoniae antibodies (AMA) in asthmatic subjects compared with nonasthmatic controls. However, concentrations of specific IgG correlated with specific IgE AMA (rho = 0.49, P = 0.0017). Asthmatic subjects had higher levels of specific IgM AMA levels compared with nonasthmatics (median [interquartile range]: 0.57 [1.00] versus 0.21 [0.19]; Kruskal-Wallis test, P = 0.0008). In addition, IgM positivity was significantly higher in asthmatic compared with nonasthmatic subjects (39.1% versus 0.0%; Fisher's exact test, P = 0.01). These results were independent of URTI history in the past 6 months, which was not associated with higher IgM, IgG or IgE AMA levels compared with no URTI history (P = 0.25-0.64). CONCLUSIONS: Increased specific IgM anti-M. pneumoniae responses may indicate an important role for M. pneumoniae infection in asthma.

Evaluation of hospital mass screening and infection control practices in a pandemic influenza full-scale exercise.

OBJECTIVE: Nonpharmacologic interventions such as limiting nosocomial spread have been suggested for mitigation of respiratory epidemics at health care facilities. This observational study tested the efficacy of a mass screening, isolation, and triage protocol in correctly identifying and placing in a cohort exercise subjects according to case status in the emergency departments at 3 acute care hospitals in Brooklyn, New York, during a simulated pandemic influenza outbreak. METHODS: During a 1-day, full-scale exercise using 354 volunteer victims, variables assessing adherence to the mass screening protocol and infection control recommendations were evaluated using standardized forms. RESULTS: While all hospitals were able to apply the suggested mass screening protocol for separation based on case status, significant differences were observed in several infection control variables among participating hospitals and different hospital areas. CONCLUSIONS: Implementation of mass screening and other infection control interventions during a hospital full-scale exercise was feasible and resulted in measurable outcomes. Hospital drills may be an effective way of detecting and addressing variability in following infection control recommendations.

Treatment of chlamydial infections.

INTRODUCTION: Chlamydiae are obligate intracellular bacterial pathogens whose entry into mucosal epithelial cells is required for intracellular survival and subsequent growth. The life cycle of Chlamydia spp. and the ability to cause persistent, often subclinical infection, has major ramifications for diagnosis and treatment of C. trachomatis and C. pneumoniae infections in humans. AREAS COVERED: This up-to-date review describes the current state of knowledge of antimicrobial susceptibilities and treatment of genital infections due to C. trachomatis and respiratory infections due to C. pneumoniae. EXPERT OPINION: Chlamydiae are susceptible to antibiotics that interfere with DNA and protein synthesis, including tetracyclines, macrolides and quinolones, which are the compounds that have been most extensively studied and used for treatment of human infection. Treatment of individuals with C. trachomatis genital infection prevents sexual transmission and complications, including pelvic inflammatory disease. Treatment of pregnant women will prevent the transmission of infection to infants during delivery. The benefits of treatment of respiratory infections due to C. pneumoniae are more difficult to assess, primarily because of the lack of FDA-approved, specific diagnostic tests for detection of the organism in clinical samples. The majority of published studies have relied on serology for diagnosis, making it difficult to assess microbiologic efficacy.

In vitro activity of CEM-101, a new fluoroketolide antibiotic, against Chlamydia trachomatis and Chlamydia (Chlamydophila) pneumoniae.

The in vitro activities of CEM-101, telithromycin, azithromycin, clarithromycin, and doxycycline against 10 isolates each of Chlamydia trachomatis and Chlamydia (Chlamydophila) pneumoniae were tested. The MIC at which 90% of the isolates of both C. trachomatis and C. pneumoniae were inhibited and the minimal bactericidal concentration at which 90% of the isolates were killed by CEM-101 were 0.25 microg/ml (ranges, 0.125 to 0.5 microg/ml for C. trachomatis and 0.25 to 1.0 microg/ml for C. pneumoniae).

Lessons from the "Clean Baby 2007" pediatric decontamination drill.

OBJECTIVES: Children have unique needs and are at risk of being exposed to hazardous materials and necessitating decontamination. A drill was conducted to identify problems that arise in the decontamination of children and develop recommendations for effective age appropriate decontamination. METHODS: In a prospective, observational, multicenter, simulation exercise (drill), the authors assessed the management of patients (actors) ages 0.25-15 years and their adult guardians, who self-presented for treatment at two hospital emergency departments (EDs) (a tertiary care university hospital and an urban, municipal, level 1 trauma center) after a radiation exposure. The drill and responses of the participants were evaluated by trained observers using standardized forms and focus group interviews. RESULTS: Twenty children (aged 0-15 years, mean 10.7, median 12.0) and five adults presented to two EDs. Eighty-five percent of the children were successfully decontaminated in showers. Reasons for noncompletion included medical (respiratory distress, n = 1) and behavioral (n = 2) limitations. Sixty-five percent of children shivered and none were provided with appropriate sized covering immediately after showering. Forty percent were reluctant to undress and all children < 5 years (n = 4) needed assistance undressing and showering. Eighty-four percent received postdecontamination radiation screening and all had their contaminated belongings secured. Moods were described as happy 25 percent, cooperative 80 percent, consolable 35 percent, fearful 15 percent, and crying 10 percent. There was an association between children younger than 12 years of age and fearful mood or crying (p < 0.05). CONCLUSIONS: This drill identified several key areas of concern; including the need to maintain children's warmth by using heaters and sufficient body coverings and to increase staffing to better focus on age-specific requirements such as psychosocial needs that included anxiety, modesty, and keeping families together. These needs may compromise effective decontamination. Pediatric decontamination protocols and interventions addressing all these concerns should be further studied and implemented.

Sophorolipids as antibacterial agents.

Sophorolipids (SLs), glycolipids produced by yeasts, have been reported to have immunomodulating activity and to reduce the mortality rate in animal models of sepsis. In the present study, the antibacterial activities of SLs and several derivatives were tested against a selection of standard bacterial isolates using the broth microdilution method. The SL derivatives tested did not show any significant antibacterial activity in vitro when tested at clinically relevant concentrations. Most likely the reported decrease of mortality rate in the rat septic shock model was not secondary to antibacterial activity of SLs. The SLs may be used as anti-inflammatory agents or immunomodulators without affecting the host's bacterial flora.

Disaster preparedness: hospital decontamination and the pediatric patient--guidelines for hospitals and emergency planners.

In recent years, attention has been given to disaster preparedness for first responders and first receivers (hospitals). One such focus involves the decontamination of individuals who have fallen victim to a chemical agent from an attack or an accident involving hazardous materials. Children often are overlooked in disaster planning. Children are vulnerable and have specific medical and psychological requirements. There is a need to develop specific protocols to address pediatric patients who require decontamination at the entrance of hospital emergency departments. Currently, there are no published resources that meet this need. An expert panel convened by the New York City Department of Health and Mental Hygiene developed policies and procedures for the decontamination of pediatric patients. The panel was comprised of experts from a variety of medical and psychosocial areas. Using an iterative process, the panel created guidelines that were approved by the stakeholders and are presented in this paper. These guidelines must be utilized, studied, and modified to increase the likelihood that they will work during an emergency situation.

In vitro models of acute and long-term continuous infection of human respiratory epithelial cells with Chlamydophila pneumoniae have opposing effects on host cell apoptosis.

Persistent infection with the obligate intracellular pathogen Chlamydophila pneumoniae has been implicated in the pathogenesis of many chronic diseases, but its mechanism remains unclear. Many pathogens have been found to modulate cellular apoptosis in order to survive and multiply. Chlamydial species were shown to both induce and inhibit host cell apoptosis depending on the experimental conditions. We utilized in vitro models of acute and long-term continuous (LTC) infection with the same cell line (HEp-2) and chlamydial isolate (TW-183) used in both models. Host cell apoptosis in infected and uninfected cells was assessed by fluorescence microscopy and flow cytometry. While acute infection induced apoptosis 72 h post-infection, LTC-infected cells had low rates of apoptosis and showed resistance to different exogenous inducers of apoptosis (sorbitol, serum withdrawal, hydrogen peroxide) when compared to uninfected cells. Chronicity of infection appears to be a critical factor in the modulation of host cell apoptosis by C. pneumoniae. Induction of apoptosis may help to propagate the infection, while inhibition of apoptosis could help protect the organism in chronic infection.

Iclaprim.

Iclaprim is a novel diaminopyrimidine, and an inhibitor of dihydrofolate reductase, which has shown potent, extended-spectrum in vitro activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, vancomycin-intermediate and vancomycin-resistant S. aureus and macrolide-, quinolone- and trimethoprim-resistant strains. In addition, iclaprim has demonstrated activity against Streptococcus pneumoniae including penicillin-, erythromycin-, levofloxacin- and trimethoprim/sulfamethoxazole-resistant strains. Furthermore, in vitro activity has also been observed against Gram-negative bacteria and atypical bacteria. The pharmaco-kinetic profile of this agent reveals that iclaprim is available for intravenous and oral use, with good oral bioavailability. Phase II clinical trials have shown promise in its use for complicated skin and skin structure infections that are caused by methicillin-resistant S. aureus and two Phase III clinical trials have been recently completed for the same indication. Phase II trials evaluating the efficacy in respiratory infections are expected to start in 2007. At this early point in clinical development, the available reported data indicate potential for iclaprim as a new antibiotic for parenteral and oral treatment of complicated skin and skin structure infections.