Antibacterial resistance leadership group: open for business.

Funded by the National Institute of Allergy and Infectious Diseases, the Antibacterial Resistance Leadership Group (ARLG) is tasked with developing a clinical research agenda and conducting clinical studies to address the growing public health threat of antibacterial resistance. The ARLG has identified 4 high-priority areas of research: infections caused by gram-negative bacteria, infections caused by gram-positive bacteria, antimicrobial stewardship and infection prevention, and diagnostics. The ARLG will be accepting proposals from the scientific community for clinical research that addresses 1 or more of these high-priority areas. These studies should have the potential to transform medical practice and be unlikely to occur without ARLG support. The purpose of this article is to make interested parties aware of clinical research opportunities made available by ARLG and to encourage submission of clinical research proposals that address the problem of antibacterial resistance.

Colistin Monotherapy versus Combination Therapy for Carbapenem-Resistant Organisms.

BACKGROUND: Pneumonia and bloodstream infections (BSI) due to extensively drug-resistant (XDR) Acinetobacter baumannii, XDR Pseudomonas aeruginosa, and carbapenem-resistant Enterobacterales (CRE) are associated with high mortality rates, and therapeutic options remain limited. This trial assessed whether combination therapy with colistin and meropenem was superior to colistin monotherapy for the treatment of these infections. METHODS: The OVERCOME (Colistin Monotherapy versus Combination Therapy) trial was an international, randomized, double-blind, placebo-controlled trial. We randomly assigned participants to receive colistin (5 mg/kg once followed by 1.67 mg/kg every 8 hours) in combination with either meropenem (1000 mg every 8 hours) or matching placebo for the treatment of pneumonia and/or BSI caused by XDR A. baumannii, XDR P. aeruginosa, or CRE. The primary outcome was 28-day mortality, and secondary outcomes included clinical failure and microbiologic cure. RESULTS: Between 2012 and 2020, a total of 464 participants were randomly assigned to treatment, and 423 eligible patients comprised the modified intention-to-treat population. A. baumannii was the predominant trial pathogen (78%) and pneumonia the most common index infection (70%). Most patients were in the intensive care unit at the time of enrollment (69%). There was no difference in mortality (43 vs. 37%; P=0.17), clinical failure (65 vs. 58%; difference, 6.8 percentage points; 95% confidence interval [CI], -3.1 to 16.6), microbiologic cure (65 vs. 60%; difference, 4.8 percentage points; 95% CI, -5.6 to 15.2), or adverse events (acute kidney injury, 52 vs. 49% [P=0.55]; hypersensitivity reaction, 1 vs. 3% [P=0.22]; and neurotoxicity, 5 vs. 2% [P=0.29]) between patients receiving monotherapy and combination therapy, respectively. CONCLUSIONS: Combination therapy with colistin and meropenem was not superior to colistin monotherapy for the treatment of pneumonia or BSI caused by these pathogens. (Funded by the National Institute of Allergy and Infectious Diseases, Division of Microbiology and Infectious Diseases protocol 10-0065; ClinicalTrials.gov number, NCT01597973.).

Predictors of in-hospital mortality in a cohort of people living with HIV (PLHIV) admitted to an academic medical intensive care unit from 2009 to 2014: A retrospective cohort study.

Outcomes for critically ill people living with human immunodeficiency virus (PLHIV) have changed with the use of antiretroviral therapy (ART). To identify these outcomes and correlates of mortality in a contemporary critically ill cohort in an urban academic medical center in Baltimore, a city with a high burden of HIV, we conducted a retrospective cohort study of individuals admitted to a medical intensive care unit (MICU) at a tertiary care center between 2009 and 2014. PLHIV who were at least 18 years of age with an index MICU admission of ≥24 hours during the 5-year study period were included in this analysis. Data were obtained for participants from the time of MICU admission until hospital discharge and up to 180 days after MICU admission. Logistic regression was used to identify independent predictors of hospital mortality. Between June 2009 and June 2014, 318 PLHIV admitted to the MICU met inclusion criteria. Eighty-six percent of the patients were non-Hispanic Blacks. Poorly controlled HIV was very common with 70.2% of patients having a CD4 cell count <200 cells/mm3 within 3 months prior to admission and only 34% of patients having an undetectable HIV viral load. Hospital mortality for the cohort was 17%. In a univariate model, mortality did not differ by demographic variables, CD4 cell count, HIV viral load, or ART use. Regression analysis adjusted by relevant covariates revealed that MICU patients admitted from the hospital ward were 6.4 times more likely to die in hospital than those admitted from emergency department. Other positive predictors were a diagnosis of end-stage liver disease, cardiac arrest, ventilator-dependent respiratory failure, vasopressor requirement, non-Hodgkin lymphoma, and symptomatic cytomegalovirus disease. In conclusion, in this critically ill cohort with HIV infection, most predictors of mortality were not directly related to HIV and were similar to those for the general population.

Infantile hypertrophic pyloric stenosis before 3 weeks of age in infants and preterm babies.

BACKGROUND: Most infantile hypertrophic pyloric stenosis (IHPS) cases are diagnosed between 3 and 12 weeks after birth. Few data exist regarding Asian infants with IHPS who are younger than 3 weeks or are preterm. The goal of this study is to identify unusual clinical manifestations, clinical course, duration of hospital stay, and complications of Asian infants with IHPS who are preterm or younger than 3 weeks of age. METHODS: From 1991 to 2004, all IHPS patients admitted to three tertiary centers in southern Taiwan were enrolled. The clinical manifestations, duration of hospital stay and complications were further compared between the IHPS patients diagnosed before and after 3 weeks; preterm and term infants. RESULTS: A total of 214 patients were enrolled into the study; the mean age of diagnosis was 40 days of age; the average duration of hospital stay was 6.27 days. Eighteen (8.41%) patients were diagnosed before 3 weeks of age. A significantly shorter timeframe of diagnosis, a higher rate of jaundice, a lower daily body weight gain and longer duration of hospital stay were noted in the IHPS group prior to 3 weeks compared with those in IHPS group after 3 weeks. Eighteen were preterm infants. A significantly older age of symptom onset, a lower body weight at admission, more cases diagnosed by barium meal study and higher postoperative complication rates were noted in the preterm group versus full-term infants with IHPS. CONCLUSIONS: The IHPS cases diagnosed before 3 weeks of age had longer duration of hospital stay. Preterm infants with IHPS had more postoperative complications.

Impact of Coronavirus Disease 2019 Pandemic on Viral Hepatitis Elimination: What Is the Price?

In 2016, the World Health Organization developed a plan for viral hepatitis elimination by 2030. Globally, control of hepatitis B virus (HBV) and hepatitis C virus (HCV) are the most challenging aspects of viral hepatitis elimination. In many developed countries elimination of HBV could be targeted to special populations mostly immigrants from low resource settings. Elimination of HCV, however, remains a challenge globally. Barriers to HCV elimination include high cost of medications and the ability to engage specific at-risk populations as well as individuals who are out of medical care. In the context of the coronavirus disease 2019 (COVID-19) pandemic, treatment access and screening have been further negatively impacted by social distancing rules and COVID-19-related anxieties. This threatens to throw most countries off course in their elimination efforts. Before the pandemic, some states in the United States had scaled up their elimination efforts with plans to ramp up testing and treatment using Netflix-like payment models for HCV direct acting antiviral drugs. Most of these efforts have stalled on account of the health system's focus on COVID-19 control. To prevent further delays in achieving elimination targets, programs would need to explore new models of care that address COVID-19-related access hurdles. Systems that leverage technologies such as telemedicine and self-testing could help maintain treatment levels. Mathematical models estimate that COVID-19-related delays in 2020 could lead to 44,800 hepatocellular cancers and 72,300 liver-related deaths for the next decade.

Comparison of macular thickness measurement and segmentation error rate between stratus and fourier-domain optical coherence tomography.

BACKGROUND AND OBJECTIVE: To compare macular thickness measurements and segmentation error rates between Stratus optical coherence tomography (OCT) (Carl Zeiss Meditec, Inc., Dublin, CA), and Fourier-domain OCT (RTVue, Optovue, Inc., Fremont, CA). PATIENTS AND METHODS: A retrospective study was performed of 93 normal and pathologic eyes from 79 subjects imaged with both OCT instruments on the same day. Both the macular thickness measurement for each Early Treatment Diabetic Retinopathy Study (ETDRS) zone and the incidence of segmentation error in the central macula between the two instruments were compared. RESULTS: Macular thickness measurements for all nine ETDRS zones were higher with RTVue compared with Stratus OCT (P < .01). Linear regression analysis showed the highest correlation in the central macula (R(2) = 0.88), with progressively lower correlation peripherally. The overall segmentation error rate was 29% with Stratus OCT versus 32% with RTVue (P > .05). CONCLUSION: Macular thickness measurement was greater with RTVue than with Stratus OCT in all ETDRS areas, with the best correlation seen in the central macula. No difference in segmentation error rate was noted between the two instruments.

Zygomycosis in children: a systematic review and analysis of reported cases.

BACKGROUND: Zygomycosis has emerged as an increasingly important infection with a high mortality especially in immunocompromised patients. No comprehensive analysis of pediatric zygomycosis cases has been published to date. METHODS: We used a PUBMED search for English publications of pediatric (0-18 years) zygomycosis cases and references from major books as well as single case reports or case series. Individual references were reviewed for additional cases. Data were entered into Filemaker-pro database and analyzed by logistic regression analysis. RESULTS: One hundred fifty-seven cases (64% male) were found with median age 5 years (range, 0.16-13). Underlying conditions included neutropenia (18%), prematurity (17%), diabetes mellitus (15%), ketoacidosis (10%), and no apparent underlying condition (14%). The most common patterns of zygomycosis were cutaneous (27%), gastrointestinal (21%), rhinocerebral (18%), and pulmonary (16%). Among 77 culture-confirmed cases, Rhizopus spp. (44%) and Mucor spp. (15%) were most commonly identified. Of 81 patients who were given antifungal therapy, 73% received an amphotericin B formulation only. The remaining patients received mostly amphotericin B in combination with other antifungal agents. Mortality in patients without antifungal therapy was higher than in those with therapy (88% versus 36%, P < 0.0001). Ninety-two (59%) patients underwent surgery. Cerebral, gastrointestinal, disseminated and cutaneous zygomycosis were associated with mortality rates of 100, 100, 88, and 0%, respectively. Independent risk factors for death were disseminated infection (OR: 7.18; 95% CI: 3.02-36.59) and age <1 year (OR: 3.85; 95% CI: 1.05-7.43). Antifungal therapy and particularly surgery reduced risk of death by 92% (OR: 0.07; 95% CI: 0.04-0.25) and 84% (OR: 0.16; 95% CI: 0.09-0.61), respectively. CONCLUSIONS: Zygomycosis is a life-threatening infection in children with neutropenia, diabetes mellitus, and prematurity as common predisposing factors, and there is high mortality in untreated disease, disseminated infection, and age <1 year. Amphotericin B and surgery significantly improve outcome.

Streptococcus pneumoniae bacteraemia: pharmacodynamic correlations with outcome and macrolide resistance--a controlled study.

There are few data on macrolide pharmacodynamics in pneumococcal infections. We evaluated pneumococcal area under the inhibitory concentration-time curve (AUIC) values at the point of hospital admission in 59 bacteraemic patients failing in the community and in 98 bacteraemic controls without macrolide exposure. The area under the 24-h concentration-time curve (AUC24) was calculated for each patient using age, weight and daily dose; using minimum inhibitory concentrations (MICs), the values of AUIC (i.e. AUC24/MIC) were then computed. Clinical and outcome information was also collected in hospital. Five of six patients who died of pneumococcal bacteraemia in hospital received azithromycin, with a mean AUIC of 8.1 prior to hospital admission. Resistant isolates were recovered in 35 (59%) macrolide failures and in only 28 (29%) controls (P=0.001). Azithromycin AUICs averaged 10 in failure patients and 17 in controls. For clarithromycin and erythromycin, the mean AUIC values in failures were 31 and 53, respectively, and the AUIC in controls was >100. Low AUIC values against Streptococcus pneumoniae precede macrolide failures in the community. Patient factors do not predict these outcomes and thus the most likely explanation for macrolide failure in the community is inadequate macrolide activity in patients who receive these antibiotics for treatment of organisms that are not sufficiently susceptible.

Problem pathogens: paediatric legionellosis--implications for improved diagnosis.

Legionnaires' disease is an established and frequent cause of pneumonia in adults but is thought to be a rare cause in children. We reviewed the medical literature for cases of Legionnaires' disease in children and analysed the epidemiology, clinical characteristics, and treatment. 76 cases of legionella infection in children were identified. In 56%, diagnosis was made with culture methodology. 46% were community-acquired infections. 51.5% were under 2 years of age. 78% of the patients had an underlying condition such as malignancy. Fever, cough, and tachypnoea were the most common symptoms. The overall mortality rate was 33% and was higher in immunosuppressed children and in children younger than the age of 1 year. Patients who were treated empirically with anti-legionella therapy had a notably lower mortality rate compared with patients on inappropriate therapy (23%vs 70%). In 88% of hospital-acquired cases, an environmental link to potable water colonised with legionella was identified. We found no clinical features unique to Legionnaires' disease in children that would allow differentiation from pneumonia due to other respiratory pathogens. Awareness of legionella as a potential cause of paediatric pneumonia is particularly important because infection can be severe and life threatening and antimicrobial therapy often used for empirical therapy in children is not effective against legionella. In any case of pneumonia unresponsive to antibiotics, Legionnaires' disease should be considered and specific diagnostic tests to verify this diagnosis should be done. As legionella diagnostic tests become more widely applied, we predict that legionellosis may appear as an emerging infectious disease in children.

Serotype and antimicrobial resistance patterns of Streptococcus pneumoniae isolated from Taiwanese children: comparison of nasopharyngeal and clinical isolates.

This report describes the serotypes and antimicrobial resistance patterns of 860 strains of Streptococcus pneumoniae isolated from nasopharyngeal (NP) carriers and clinical specimens collected from Taiwanese children during the years 1997 to 2003. The 6 most common serotypes/groups were 23F, 19F, 6B, 14, 6A, and 3. These accounted for 652/716 (91.1%) of the NP and 131/144 (91.0%) of the clinical isolates. Serotype 23F was the most common isolate in the NP carriers (25.7%, 184/716). Serogroup14 was most common in the clinical isolates (29.2%, 42/144) and the most frequent invasive isolate (43.4%, 33/76). It was more frequently associated with invasive infection than all other serotypes/groups (odds ratio = 7.2; 95% confidence interval, 4.16-12.46; P < .0001). Resistance to macrolides was high in all serotypes/groups, which ranged from 70% to 97%. Resistance to penicillin varied among the 6 leading serotypes/groups, ranging from 3% in serogroup 3 to 99% in serotype 19F. Serotype 23F was most likely to be multidrug resistant to penicillin, macrolides, and chloramphenicol compared with all others (107/150 [71%] versus 105/461 [23%], P < .0001). The potential coverage by the pentavalent and heptavalent vaccines was 83% for all isolates, but was significantly lower for NP than clinical isolates (81% versus 92%, P< .01). These findings provide baseline data to compare trends in the distribution of pneumococcal serotypes and antibiotic resistance patterns with the introduction of childhood pneumococcal vaccination in Taiwan and other countries.

Epidemiology and outcome of zygomycosis: a review of 929 reported cases.

BACKGROUND: Zygomycosis is an increasingly emerging life-threatening infection. There is no single comprehensive literature review that describes the epidemiology and outcome of this disease. METHODS: We reviewed reports of zygomycosis in the English-language literature since 1885 and analyzed 929 eligible cases. We included in the database only those cases for which the underlying condition, the pattern of infection, the surgical and antifungal treatments, and survival were described. RESULTS: The mean age of patients was 38.8 years; 65% were male. The prevalence and overall mortality were 36% and 44%, respectively, for diabetes; 19% and 35%, respectively, for no underlying condition; and 17% and 66%, respectively, for malignancy. The most common types of infection were sinus (39%), pulmonary (24%), and cutaneous (19%). Dissemination developed in 23% of cases. Mortality varied with the site of infection: 96% of patients with disseminated disease died, 85% with gastrointestinal infection died, and 76% with pulmonary infection died. The majority of patients with malignancy (92 [60%] of 154) had pulmonary disease, whereas the majority of patients with diabetes (222 [66%] of 337) had sinus disease. Rhinocerebral disease was seen more frequently in patients with diabetes (145 [33%] of 337), compared with patients with malignancy (6 [4%] of 154). Hematogenous dissemination to skin was rare; however, 78 (44%) of 176 cutaneous infections were complicated by deep extension or dissemination. Survival was 3% (8 of 241 patients) for cases that were not treated, 61% (324 of 532) for cases treated with amphotericin B deoxycholate, 57% (51 of 90) for cases treated with surgery alone, and 70% (328 of 470) for cases treated with antifungal therapy and surgery. By multivariate analysis, infection due to Cunninghamella species and disseminated disease were independently associated with increased rates of death (odds ratios, 2.78 and 11.2, respectively). CONCLUSIONS: Outcome from zygomycosis varies as a function of the underlying condition, site of infection, and use of antifungal therapy.

High carriage rate of high-level penicillin-resistant Streptococcus pneumoniae in a Taiwan kindergarten associated with a case of pneumococcal meningitis.

BACKGROUND: The Taiwan19F-14 Streptococcus pneumoniae clone and its variants are being found with increasing frequency in the Asia-Pacific region. A 5-year old child with S. pneumoniae meningitis caused by a high-level penicillin resistant strain (MIC = 4 microg/ml) was admitted to a hospital in southern Taiwan. We carried out a study to determine the potential source of this strain. METHODS: Nasopharyngeal cultures were obtained from all children attending the same kindergarten as the index case. To determine their relatedness all isolates were compared by serotype, antimicrobial susceptibility profile and pulsed field gel electrophoresis (PFGE). RESULTS: A high proportion of the children including the index case (32/78, 41.0%) carried S. pneumoniae in their nasopharynx (NP). The most common serotype was 19F (13/32, 40.6%). The PFGE types of the 19F serotype isolates obtained from the patient's blood, CSF and NP were identical and were related to 11 other serotype 19F NP isolates including 10 that were indistinguishable from the Taiwan19F-14 clone. All 14 isolates had similar high-level penicillin and multi-drug resistance. The serotypes of the other 19 NP isolates included 6A (2), 6B (10), 23F (5), 9V (1) and 3 (1). The overall rate of penicillin resistance in these S. pneumoniae from these children was 87.5% (28/32), with an MIC50 of 2 and MIC90 of 4 ug/ml. In addition, multi-drug resistant-isolates (isolates resistant to 3 different classes of antimicrobials) accounted for 87.5% (28/32) of all isolates. CONCLUSION: The high carriage rate of high-level penicillin- and multi-drug- resistant S. pneumoniae in a kindergarten associated with a case of pneumococcal meningitis emphasizes the need for restraint in antibiotic use and consideration of childhood immunization with conjugate pneumococcal vaccine to prevent the further spread of resistant S. pneumoniae in Taiwan.

An international prospective study of pneumococcal bacteremia: correlation with in vitro resistance, antibiotics administered, and clinical outcome.

We performed a prospective, international, observational study of 844 hospitalized patients with blood cultures positive for Streptococcus pneumoniae. Fifteen percent of isolates had in vitro intermediate susceptibility to penicillin (minimum inhibitory concentration [MIC], 0.12-1 microg/mL), and 9.6% of isolates were resistant (MIC, >or=2 microg/mL). Age, severity of illness, and underlying disease with immunosuppression were significantly associated with mortality; penicillin resistance was not a risk factor for mortality. The impact of concordant antibiotic therapy (i.e., receipt of a single antibiotic with in vitro activity against S. pneumoniae) versus discordant therapy (inactive in vitro) on mortality was assessed at 14 days. Discordant therapy with penicillins, cefotaxime, and ceftriaxone (but not cefuroxime) did not result in a higher mortality rate. Similarly, time required for defervescence and frequency of suppurative complications were not associated with concordance of beta-lactam antibiotic therapy. beta-Lactam antibiotics should still be useful for treatment of pneumococcal infections that do not involve cerebrospinal fluid, regardless of in vitro susceptibility, as determined by current NCCLS breakpoints.

Newer systemic antifungal agents : pharmacokinetics, safety and efficacy.

The past few years have seen the advent of several new antifungal agents, including those of a new class and a new generation of an existing class. Caspofungin, the first available echinocandin, has greatly expanded the antifungal armamentarium by providing a cell wall-active agent with candidacidal activity as well as demonstrated clinical efficacy in the therapy of aspergillosis refractory to available therapy. In addition, in clinical trials, caspofungin had comparable efficacy to amphotericin B for candidaemia and invasive Candida infections. Caspofungin and two more recently introduced echinocandins, micafungin and anidulafungin, are available as intravenous formulations only and characterised by potent anti-candidal activity, as well as few adverse events and drug interactions. Voriconazole, the first available second-generation triazole, available in both intravenous and oral formulations, has added a new and improved therapeutic option for primary therapy of invasive aspergillosis and salvage therapy for yeasts and other moulds. In a randomised trial, voriconazole demonstrated superior efficacy and a survival benefit compared with amphotericin B followed by other licensed antifungal therapy. This and data from a noncomparative study led to voriconazole becoming a new standard of therapy for invasive aspergillosis. Voriconazole has several important safety issues, including visual adverse events, hepatic enzyme elevation and skin reactions, as well as a number of drug interactions. Posaconazole, only available orally and requiring dose administration four times daily, shows encouraging efficacy in difficult to treat infections due to zygomycetes. Ravuconazole, available in both intravenous and oral formulations, has broad-spectrum in vitro potency and in vivo efficacy against a wide range of fungal pathogens. Clinical studies are underway. Despite the advances offered with each of these drugs, the morbidity and mortality associated with invasive fungal infections remains unacceptable, especially for the most at-risk patients. For individuals with severe immunosuppression as a result of chemotherapy, graft-versus-host disease and its therapy, or transplantation, new drugs and strategies are greatly needed.

Esophageal candidiasis in human immunodeficiency virus-infected pediatric patients after the introduction of highly active antiretroviral therapy.

OBJECTIVE: To investigate epidemiologic trends, clinical features and outcome of esophageal candidiasis in the era of highly active antiretroviral therapy in a prospectively monitored population of HIV-infected children and adolescents followed at the National Cancer Institute. PATIENTS AND METHODS: The records of all HIV-infected pediatric patients (n = 266) followed between 1995 and 2000 were reviewed for a history of esophageal candidiasis. Proven esophageal candidiasis was defined as clinical plus radiographic and/or endoscopic findings of esophageal candidiasis. Probable esophageal candidiasis was defined as esophageal symptoms that responded promptly to appropriate antifungal therapy. The medical records of all patients fulfilling these criteria were reviewed for demographic, clinical and laboratory features at presentation, as well as therapeutic interventions and outcome. RESULTS: Of the 266 patients 9 (3.4%) had 18 documented episodes of proven (n = 16) or probable (n = 2) esophageal candidiasis. A history of prior mucosal candidiasis was present in 94% of all episodes. The median CD4+ count at the time of diagnosis was 7/microl (range, 0 to 550), and the median viral load was 98000 copies/ml (range, 22916 to 1278933). Concurrent oropharyngeal candidiasis was the most common clinical presentation (72%) followed by fever (55%), odynophagia (50%) and nausea or vomiting (39%). Treatment consisted of antifungal triazoles (61%) or amphotericin B (39%). Clinical cure was achieved in 15 cases, including all patients receiving triazoles. CONCLUSION: Esophageal candidiasis persists in the subgroup of patients not responding to highly active antiretroviral therapy and in that setting may present without concomitant oropharyngeal candidiasis or typical clinical symptoms, thus underscoring the need for a high index of suspicion in children with very low CD4+ counts.

Necrotizing pneumonitis caused by Mycoplasma pneumoniae in pediatric patients: report of five cases and review of literature.

Mycoplasma pneumoniae infection is usually self-limited without severe sequelae. We report 5 pediatric patients with necrotizing pneumonitis caused by Mycoplasma pneumoniae and reviewed the reported cases in the English language. Protracted course of fever and respiratory distress were noted in all 5 patients. Macrolides and adequate chest tube drainage for pleural effusion were the mainstay of treatment.

Endocarditis caused by penicillin-resistant Streptococcus mitis in a 12-year-old boy.

A case of congenital coronary arteriovenous fistula with infective endocarditis caused by penicillin-resistant Streptococcus mitis is reported. Lack of prophylactic antibiotics during dental procedure may cause the development of endocarditis. Bactericidal test (Schlichter test) was performed to guide the therapy for this case of bacterial endocarditis caused by penicillin-resistant viridans streptococci. This case highlights the importance of antibiotic prophylaxis in patients with underlying heart disease undergoing dental procedures.

Pneumococcal infection in children: rational antibiotic choice for drug-resistant Streptococcus pneumoniae.

Streptococcus pneumoniae is one of the most common bacterial causes of otitis media, sinusitis, bacteremia, pneumonia and bacterial meningitis in the pediatric population. The resistance of S. pneumoniae to penicillin and other antimicrobial agents is increasing in many parts of the world. In Taiwan, extremely high prevalence (70%) of penicillin-resistant S. pneumoniae among children with nasopharyngeal carriage has been reported. The mechanism of resistance to penicillin is the alteration of penicillin binding protein (PBP) instead of the production of beta-lactamase. Thus beta-lactamase inhibitors are not the solution to the treatment of infections caused by penicillin-resistant S. pneumoniae. The adequate treatment of infections caused by penicillin-resistant S. pneumoniae should be based on (1) site of infection (2) degree of resistance. Currently, the MIC breakpoints for S. pneumoniae are divided to 2 categories; one for CNS infection and the other for non-CNS infections. For non-CNS infections caused by susceptible or intermediate S. pneumoniae, penicillin still remains the drug of choice with excellent bactericidal activity. Vancomycin should not be the first choice in treating all pneumococcal infections.

The clinical outcomes of antimicrobial therapy in pediatric patients with nontyphoid salmonellosis with different levels of severity.

BACKGROUND: To evaluate if a severity score could differentiate the severity of children with nontyphoid salmonellosis; clinical outcomes of antimicrobial therapy in nontyphoid salmonellosis children with different severities. METHODS: Admitted children with nontyphoid salmonellosis from 1996 to 2009 were monitored. Enrolled patients were divided into no antibiotics, concordant, and discordant therapies. Besides, the patients were classified into mild, moderate, and severe group according to the severity score. Clinical outcomes were compared among them. RESULTS: A total of 558 patients were enrolled. In no therapy subset, compared with mild group, patients had worse clinical outcomes and more complications in severe group. Patients receiving no therapy had better clinical outcomes in mild group. However, patients receiving concordant therapy (ceftriaxone) had better clinical outcomes in severe group. CONCLUSIONS: The severity score and local antibiotic susceptibility could serve as guides for antibiotic prescription for severe nontyphoid salmonellosis in children. Inappropriate antibiotic use would worsen clinical outcomes in children with mild nontyphoid salmonellosis.

Early administration of probiotic Lactobacillus acidophilus and/or prebiotic inulin attenuates pathogen-mediated intestinal inflammation and Smad 7 cell signaling.

Immaturity of gut-associated immunity may contribute to pediatric mortality associated with enteric infections. A murine model to parallel infantile enteric disease was used to determine the effects of probiotic, Lactobacillus acidophilus (La), prebiotic, inulin, or both (synbiotic, syn) on pathogen-induced inflammatory responses, NF-κB, and Smad 7 signaling. Newborn mice were inoculated bi-weekly for 4 weeks with La, inulin, or syn and challenged with Citrobacter rodentium (Cr) at 5 weeks. Mouse intestinal epithelial cells (CMT93) were exposed to Cr to determine temporal alterations in NF-Kappa B and Smad 7 levels. Mice with pretreatment of La, inulin, and syn show reduced intestinal inflammation following Cr infection compared with controls, which is associated with significantly reduced bacterial colonization in La, inulin, and syn animals. Our results further show that host defense against Cr infection correlated with enhanced colonic IL-10 and transforming growth factor-ß expression and inhibition of NF-κB in syn-treated mice, whereas mice pretreated with syn, La, or inulin had attenuation of Cr-induced Smad 7 expression. There was a temporal Smad 7 and NF-κB intracellular accumulation post-Cr infection and post-tumor necrosis factor stimulation in CMT93 cells. These results, therefore, suggest that probiotic, La, prebiotic inulin, or synbiotic may promote host-protective immunity and attenuate Cr-induced intestinal inflammation through mechanisms affecting NF-κB and Smad 7 signaling.