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Contact lens-associated microbial keratitis.

During a 14-year period, 42 cases of microbial keratitis were associated with contact lens (CL) wear. Pseudomonas aeruginosa was isolated in 40% of the cases and Staphylococcus in 31%; Streptococcus pneumoniae, alpha-hemolytic Streptococcus, and Serratia marcescens were the next most commonly isolated pathogens. There was a single fungal corneal ulcer. Bandage CL use was associated with a high prevalence of infection with quasi-commensal organisms and with polymicrobial keratitis, a pattern of disease quite distinct from that induced by other types of CLs. Marked visual loss frequently occurred. There was a disturbing increase in the number of infections associated with extended-wear CLs (worn for either aphakia or myopia) over the last 18 months of the study.

Adolescent↗

Microbiologic characteristics of persistent otitis media.

OBJECTIVE: To identify the pathogens isolated from children with acute otitis media who did not respond to antimicrobial drug therapy. METHODS: Retrospective analysis of cultures obtained by tympanocentesis from 46 children. RESULTS: Organisms were recovered from 34 children (74%), and 43 isolates were recovered from these individuals. The organisms were Streptococcus pneumoniae (16 isolates), Haemophilus influenzae non-type b (12 isolates), Moraxella catarrhalis (5 isolates), Streptococcus pyogenes (5 isolates), Staphylococcus aureus (3 isolates), and Peptostreptococcus species (2 isolates). Resistance to the antimicrobial agent used was found in 27 (63%) of 43 isolates found in 22 patients (48%). Of patients who did not respond to amoxicillin therapy, H influenzae predominated. Streptococcus pneumoniae was recovered from 5 (56%) of 9 of those who did not respond to trimethoprim and sulfamethoxazole therapy, 4 (44%) of 9 patients after azithromycin therapy, 3 (25%) of 12 patients after amoxicillin therapy, and 2 (40%) of 5 patients after cefixime therapy. Streptococcus pyogenes was recovered from 2 (40%) of 5 patients after trimethoprim and sulfamethoxazole therapy and from 2 (40%) of 5 patients after cefixime therapy. CONCLUSIONS: The data illustrate the relation between resistance to antimicrobial drug therapy and failure of patients with otitis media to improve. They also highlight the importance of diagnostic tympanocentesis in establishing the presence of resistant microorganisms.

Acute Disease↗

Efficacy of two third-generation cephalosporins in prophylaxis for head and neck surgery.

Optimal antimicrobial prophylaxis during head and neck surgery is as yet unclear. The semisynthetic third-generation cephalosporin antibiotics would appear to have potential usefulness because of their broad antibacterial spectrum, favorable pharmacokinetic properties, and record of safety. Eighty patients were prospectively randomized into this placebo-controlled, double-blind study to receive either placebo, cefoperazone sodium, or cefotaxime sodium preoperatively and for 24 hours postoperatively. Infection rates were 78% for the placebo group and 10% for the group receiving the cephalosporin antibiotics. Infections were polymicrobial. Anaerobic bacteria constituted 42% of the pathogens isolated. Wound and serum antibiotic concentrations exceeded the minimal inhibitory concentration of the bacterial flora. This study establishes the necessity of antimicrobial prophylaxis for contaminated oncologic procedures of the head and neck. Our experience indicates that cefoperazone and cefotaxime are particularly useful.

Bacteria↗

Acute bacterial sinusitis. Minocycline vs amoxicillin.

The efficacy and safety of minocycline were compared with that of amoxicillin in the treatment of 58 patients with acute bacterial sinusitis. The most frequently isolated pathogens were streptococci, staphylococci, and Haemophilus influenzae. After therapy for a mean time of 11 days, clinical cure or improvement and bacterial eradication were evident in 100% of the patients treated with minocycline and in 95% of the patients treated with amoxicillin. Roentgenographic results indicated clearing or improvement in 91% of the minocycline recipients and in 70% of those who received amoxicillin. These differences between treatments were not statistically significant. A low incidence of generally mild adverse clinical experiences occurred in both treatment groups. Thus, minocycline and amoxicillin were equally safe and effective in the treatment of these patients with acute bacterial sinusitis.

Adolescent↗

Inflammatory mediators in chronic otitis media with effusion.

Otitis media with effusion (OME) is a common middle ear inflammatory disease in the pediatric population. This article determines concentrations of three functionally and metabolically distinct inflammatory mediators in middle ear effusions (MEE) and corresponding plasma of children with OME. One hundred two patients (mean age, 4.9 years) with persistent OME were studied. Middle ear effusions were collected from all subjects and plasma from a subset at the time of tympanostomy tube insertion. Histamine was assayed radioisotopically, 13,14-dihydro-15-keto-prostaglandin F2 alpha (stable PGF2 alpha metabolite) by radioimmunoassay, and neutrophil chemotactic factor of anaphylaxis by modified Boyden chamber. Mean MEE levels of the mediators (39 +/- 13 ng/mL, 462 +/- 179 pg/mL, and 264% +/- 57% positive control, respectively) were markedly higher than those of corresponding plasma (0.5 +/- 0.1 ng/mL, 285 +/- 127 pg/mL, and 47% +/- 5% positive control, respectively). The mean histamine content of mucoid effusions (43.2 +/- 56.9 ng/mL) was significantly higher than that of purulent (22.5 +/- 10.5 ng/mL) and serous (17.9 +/- 16.8 ng/mL) effusions. Higher histamine levels were observed in effusions positive for Haemophilus influenzae when compared with those with other pathogenic isolates. The high concentrations of these mediators in MEE and their potential for inducing or sustaining the inflammatory process supports a role in the pathogenesis of OME.

Adolescent↗

Unique epidemiology of nosocomial infection in a children's hospital.

A prospective study of the epidemiology of nosocomial infections was undertaken in a large pediatric hospital. Infections were identified during a 12-month period with the use of medical record audits, indices identifying high-risk patients, and analysis of positive cultures and rapid diagnostic tests for viruses, fungi, and bacteria. The attack rate of the entire hospital population surveyed was 4.1 nosocomial infections per 100 patients discharged. In contrast with studies of patients in general hospitals that included comparatively few children, the most common sites of nosocomial infections were the respiratory and gastrointestinal tracts. Staphylococcus aureus was the most commonly isolated pathogen. However, rotavirus was identified more frequently than Escherichia coli, and documented viral infections were more common than infections caused by gram-negative bacilli.

Child↗

Infections in a pediatric intensive care unit.

All infections occurring in a busy pediatric intensive care unit (PICU) from 1982 to 1984 were characterized by site, bacteriology, acquisition status, and outcome. Standard Centers for Disease Control criteria were employed. Nine hundred sixty-five patients were admitted to the PICU. Mortality was 3.4%. Two hundred twenty-one infections occurred in 180 patients. Infection rates were 23% and 6% for total and PICU-acquired infections, respectively. Infections of the central nervous system (n = 56), lower respiratory tract (n = 53), and genitourinary tract (n = 46) made up 70% of all infections. Haemophilus influenzae (n = 39) was the most commonly isolated pathogen. Staphylococcus aureus (20%) and Klebsiella-Enterobacter-Serratia (18.3%) were most commonly noted in PICU-acquired infections. Twenty infected patients (11.1%) died in the PICU. Lower respiratory tract infections (20.5%) were associated with the highest mortality. Both PICU-acquired and community-acquired infections were associated with similar mortalities. Infected patients in a PICU have a mortality approximately 300% higher than that seen in the overall PICU population. The data presented document the importance of infection and provide information against which similar units can gauge their infection status for quality-assurance purposes.

Bacterial Infections↗

Epidemiology and prognostic determinants of bloodstream infections in surgical intensive care.

HYPOTHESIS: A set of clinical variables available at the bedside can be used to predict outcome in critically ill patients with bloodstream infection (BSI). DESIGN: A 3-year retrospective cohort study. SETTING: A surgical intensive care unit in Switzerland. PATIENTS: All patients with BSI were potentially eligible. MAIN OUTCOME MEASURES: Clinical variables, organ dysfunctions, and outcome. RESULTS: Among 4530 admissions to the surgical intensive care unit, 224 clinically significant episodes of BSI were recorded (incidence, 4.9%), with a 28-day fatality of 36%. A total of 110 patients had primary bacteremia, of which 39 (35%) were catheter related. Although gram-positive organisms were the most frequently isolated pathogens (58% [159/275]), they were associated with lower case-fatality (30%) than BSI due to gram-negative bacteria (44%). Organ dysfunctions associated with the highest risk of death were neurologic dysfunction (hazard ratio [HR], 6.9; 95% confidence interval [CI], 3.3-14.5), hepatic dysfunction (HR, 3.9; 95% CI, 2.1-7.4), and disseminated intravascular coagulation (HR, 3.0; 95% CI, 1.5-6.1). By multivariate analysis, 2 independent predictors of mortality were the APACHE II (Acute Physiology and Chronic Health Evaluation II) score at onset of BSI (HR per 1-point increase, 1.08; 95% CI, 1.04-1.12) and the number of evolving organ dysfunctions (HR, 1.4; 95% CI, 1.2-1.7). Appropriate antimicrobial therapy was associated with improved outcome (HR, 0.4; 95% CI, 0.2-0.6). CONCLUSIONS: Bloodstream infection in critically ill patients is a common and frequently fatal condition. Its outcome can be predicted by the severity of illness at onset of BSI and the number of organ dysfunctions evolving thereafter. Appropriate antimicrobial therapy is an important determinant for survival.

Adolescent↗

Effect of zinc supplementation on incidence of infections and hospital admissions in sickle cell disease (SCD).

Zinc deficiency is a common nutritional problem in adult sickle-cell disease (SCD) patients. Hyperzincuria and increased requirement of zinc due to continued hemolysis in SCD are probable bases for zinc deficiency in these patients. Zinc deficiency affects adversely T-helper1 (TH1) functions and cell mediated immunity and interleukin (IL)-2 production is decreased in zinc deficient subjects. We hypothesized that zinc supplementation will improve T-helper1 function and decrease incidence of infections in patients with SCD. We tested this hypothesis in 32 SCD subjects who were divided in three groups (Grs A, B, and C). Grs A (n = 11) and B (n = 10) were zinc deficient based on cellular zinc criteria and Gr C (n = 11) were zinc sufficient. Gr A subjects were observed for 1 year (baseline), following which they received zinc acetate (50 to 75 mg of elemental zinc orally daily) for 3 years. Gr B subjects were observed for 1 year (baseline), following which they received placebo for 1 year and then switched to zinc supplementation (50 to 75 mg of elemental zinc orally daily) for 2 years. Gr C subjects did not receive any intervention inasmuch as they were zinc sufficient. Prolonged zinc supplementation resulted in an increase in lymphocyte and granulocyte zinc (P = 0.0001), and an increase in interleukin-2 production (P = 0.0001), decreased incidence of documented bacteriologically positive infections (P = 0.0026), decreased number of hospitalizations and decreased number of vaso-occlusive pain crisis (P = 0.0001). The predominant pathogens isolated were staphylococci and streptococci involving the respiratory tract and aerobic gram-negative bacteria, particularly Escherichia coli, involving the urinary tract. Further confirmation of our observations will require prospective studies of zinc supplementation in a larger number of SCD patients.

Administration, Oral↗

Axillary lesions in patients with acute leukemia: evaluation of a preventive program.

Axillary skin lesions can cause significant morbidity in patients with acute nonlymphocytic leukemia. The incidence in relation to the level of circulating granulocytes and the microbiology of 15 such lesions among 150 patients over a three year period were determined. Lesions occurred predominantly during periods of profound granulocytopenia (0-499 cells/microliter). Gram-negative bacilli were the most common pathogens isolated from these lesions. The initiation of a supervised preventive program for 84 patients over 19 months which includes the regular swabbing of each axilla with povidone-iodine cotton sticks in addition to measures to avoid skin trauma has virtually eliminated inflammatory axillary lesions in this high risk patient population.

Acute Disease↗

Model-guided microarray implicates the retromer complex in Alzheimer's disease.

Although, in principle, gene expression profiling is well suited to isolate pathogenic molecules associated with Alzheimer's disease (AD), techniques such as microarray present unique analytic challenges when applied to disorders of the brain. Here, we addressed these challenges by first constructing a spatiotemporal model, predicting a priori how a molecule underlying AD should behave anatomically and over time. Then, guided by the model, we generated gene expression profiles of the entorhinal cortex and the dentate gyrus, harvested from the brains of AD cases and controls covering a broad age span. Among many expression differences, the retromer trafficking molecule VPS35 best conformed to the spatiotemporal model of AD. Western blotting confirmed the abnormality, establishing that VPS35 levels are reduced in brain regions selectively vulnerable to AD. VPS35 is the core molecule of the retromer trafficking complex and further analysis revealed that VPS26, another member of the complex, is also downregulated in AD. Cell culture studies, using small interfering RNAs or expression vectors, showed that VPS35 regulates Abeta peptide levels, establishing the relevance of the retromer complex to AD. Reviewing our findings in the context of recent studies suggests how downregulation of the retromer complex in AD can regulate local levels of Abeta peptide.

Adult↗

Periorbital cellulitis.

Periorbital cellulitis is a commonly occurring infectious process limited to the eyelids in the preseptal region. It occurs with greater frequency in the pediatric age group. It is important to distinguish this disease from orbital cellulitis, a potentially lethal infectious process involving the contents of the orbit. A retrospective study of clinical and laboratory data from 137 cases with orbital and periorbital cellulitis was performed. Periorbital cellulitis was documented in 98 cases (71%) in contrast to orbital cellulitis, which was noted in 39 (28%) patients. Sinusitis was the most frequently encountered predisposing factor for the development of periorbital cellulitis occurring in 29 patients. All patients with a diagnosis of periorbital cellulitis were hospitalized and received antibiotics, the majority (95%) receiving intravenous therapy. Hemophilus influenzae was the most frequently isolated pathogenic organism. It was necessary to operate on eight patients. Six patients underwent incision and drainage of an eyelid or periorbital abscess. A distinction between periorbital and orbital cellulitis is clarified. The separation of these entities on the basis of physical examination and radiographic studies is stressed.

Adolescent↗

Community-acquired bacterial pneumonia in the elderly.

Pneumonia remains the leading infectious disease-related cause of death among the elderly. Streptococcus pneumoniae is the most frequent pathogen isolated from aged individuals with community-acquired pneumonia. Other common bacteria that cause this disease include Haemophilus influenzae and Legionella pneumophila. Manifestations of pneumonia in the elderly can be subtle and result in delayed recognition and treatment. Gram stain evaluation and culture of non-contaminated expectorated sputum remain the conventional techniques to guide initial antibiotic selection. While the presence of a new infiltrate on chest X-ray confirms the clinical diagnosis of pneumonia, the radiographic appearance of the infiltrate cannot accurately define the etiologic agent. Specific therapeutic measures include administration of appropriate antibiotics, correction of fluid and electrolyte imbalances, nutritional support and treatment of concomitant disorders. Preventive measures include use of influenza vaccine, amantadine and pneumococcal vaccine.

Aged↗

Disease severity in siblings with cystic fibrosis.

Since cross-infection occurs between cystic fibrosis (CF) siblings, we hypothesized that subsequent siblings may acquire respiratory pathogens at an earlier age and have a more severe course of pulmonary disease. We studied a retrospective cohort of 31 sibling pairs from the CF database at the Hospital for Sick Children. Kaplan-Meier curves and modified log-rank tests were used to test sibling differences in age of acquisition of Pseudomonas aeruginosa (PA), Staphylococcus aureus (SA), or any positive culture. Differences in disease severity outcomes were explored. Older siblings were more likely to have both SA and any CF pathogen first isolated from respiratory culture at an older age than younger siblings (P = 0.0050 and P = 0.0008, respectively, by modified log-rank tests). However, more of the older siblings were positive on first culture at time of diagnosis, introducing an age-of-diagnosis bias. Hospitalization rates, courses of oral antibiotics, FEV(1) % predicted, and weight and height measurements were not better in the older children. No differences in clinical parameters were found between older and younger siblings. The apparent finding of younger age at first isolation of pathogens from respiratory cultures in younger siblings is likely because many older siblings were already infected with these organisms at time of diagnosis.

Age of Onset↗

Evaluation of fungicides for the control of carrot cavity spot.

Cavity spot is one of the most common and serious diseases of carrot (Daucus carota L). The disease, caused by different species of Pythium, including P. violae Chesters & Hickman, P. sulcatum Pratt & Mitchell and P. sylvaticum Campbell & Hendrix, leads to frequent high rejection rates during grading worldwide. In the area of the city of Québec, the disease is caused mainly by P. sulcatum, P. sylvaticum and P. macrosporum Vaartaja & van der Plaats-Niterink. Cavity spot can be controlled with metalaxyl, but reports are emerging that this treatment show little or no efficacy in many regions. This situation reinforces the need for alternative fungicides. The objectives of the present study were: (1) to determine the sensitivity of 14 pathogenic isolates of P. sulcatum, P. sylvaticum and P. macrosporum collected from carrots produced in the area of the city of Québec to different broad-spectrum and oomycete-specific fungicides (chlorothalonil, etridiazole, fludioxonil, fosetyl-Al, metalaxyl, zoxamide), (2) to evaluate the efficacy of the fungicides in controlling cavity spot, and (3) to evaluate the risk of resistance development of isolates with the best-performing fungicide(s). The determination of EC50 for the fungicides tested showed that most isolates were highly sensitive to both metalaxyl and zoxamide but insensitive to fludioxonil, fosetyl-Al and chlorothalonil. In greenhouse assays, only zoxamide provided significant and consistent disease control as measured by the number of cavity spot lesions caused by P. sulcatum. Investigations into the risk of resistance development to zoxamide showed that, for specific isolates, repeated exposure to the fungicide resulted in a loss of sensitivity.

Daucus carota↗

Kinetics of methionine transport and metabolism by Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense.

Methionine is an essential amino acid for both prokaryotic and eukaryotic organisms; however, little is known concerning its utilization in African trypanosomes, protozoa of the Trypanosoma brucei group. This study explored the Michaelis-Menten kinetic constants for transport and pool formation as well as metabolic utilization of methionine by two divergent strains of African trypanosomes, Trypanosoma brucei brucei (a veterinary pathogen), highly sensitive to trypanocidal agents, and Trypanosoma brucei rhodesiense (a human pathogenic isolate), highly refractory to trypanocidal arsenicals. The Michaelis-Menten constants derived by Hanes-Woolf analysis for transport of methionine for T. b. brucei and T. b. rhodesiense, respectively, were as follows: K(M) values, 1. 15 and 1.75 mM; V(max) values, 3.97 x 10(-5) and 4.86 x 10(-5) mol/L/min. Very similar values were obtained by Lineweaver-Burk analysis (K(M), 0.25 and 1.0 mM; V(max), 1 x 10(-5) and 2.0 x 10(-5) mol/L/min, T. b. brucei and T. b. rhodesiense, respectively). Cooperativity analyses by Hill (log-log) plot gave Hill coefficients (n) of 6 and 2 for T. b. brucei and T. b. rhodesiense, respectively. Cytosolic accumulation of methionine after 10-min incubation with 25 mM exogenous methionine was 1.8-fold greater in T. b. rhodesiense than T. b. brucei (2.1 vs 1.1 mM, respectively). In African trypanosomes as in their mammalian host, S-adenosylmethionine (AdoMet) is the major product of methionine metabolism. Accumulation of AdoMet was measured by HPLC analysis of cytosolic extracts incubated in the presence of increasing cytosolic methionine. In trypanosomes incubated for 10 min with saturating methionine, both organisms accumulated similar amounts of AdoMet (approximately 23 microM), but the level of trans-sulfuration products (cystathionine and cysteine) in T. b. rhodesiense was double that of T. b. brucei. Methionine incorporation during protein synthesis in T. b. brucei was 2.5 times that of T. b. rhodesiense. These results further confirm our belief that the major pathways of methionine utilization, for polyamine synthesis, protein transmethylation and the trans-sulfuration pathway, are excellent targets for chemotherapeutic intervention against African trypanosomes.

Allosteric Regulation↗

Interferon-gamma expression in macaque lymph nodes during primary infection with simian immunodeficiency virus.

Simian immunodeficiency virus (SIV) replication is rapidly downregulated in the lymph nodes (LN) of rhesus macaques after the acute stage of primary infection. The aim of this study was to evaluate a possible role of interferon-gamma (IFN-gamma) in the control of SIV replication. IFN-gamma expression was analysed by in situ hybridization in the LN of rhesus macaques that were inoculated either with a high dose or with a low dose of the pathogenic isolate SIVmac 251. The kinetics of IFN-gamma induction in LN was found to follow that of SIV replication. However, the number of IFN-gamma expressing cells was not proportional to the number of infected cells. IFN-gamma expression in LN was further quantified by competitive RT-PCR. The number of IFN-gamma mRNA molecules in LN was high for the animals of the high dose group. In the low dose group, the IFN-gamma copy number varied over 2 log10 units and was particularly low for the animals that had a high and persisting antigenaemia. The analysis of a total of 10 animals inoculated with a low dose of virus showed an inverse correlation between IFN-gamma expression in LN and peak antigenemia (P < 0.01). This study provides evidence for a marked individual variability in the IFN-gamma response to primary SIV infection and supports the notion that IFN-gamma production is inhibited at an early stage in animals that harbour a high viral load.

Animals↗

A simple procedure to differentiate ailA and ailNA gene variants among human pathogenic Yersinia enterocolitica strains.

The identification and differentiation of the two variants of the ail gene, ailA from the more virulent American serotypes (08, 013a, 13b, 018, 020, 021) and ailNA from the less virulent non-American serotypes (03, 04, 05, 06, 09, 027 and 07, 8) was studied in a panel of 32 Yersinia enterocolitica human pathogenic isolates. A 444 bp fragment corresponding to the ail gene was amplified using a PCR procedure in all tested strains. Subsequent digestion of the PCR product by Rsal and by HaeIII endonucleases, provide electrophoretic patterns that clearly discriminate ailA and ailNA variants. This non-radioactive and reliable procedure allows large clinical and epidemiological studies, and could be proposed to survey the spread of virulent clones.

Base Sequence↗