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PubMed2006

Predictors of extubation failure in patients with chronic obstructive pulmonary disease.

Few studies have focused on extubation outcome in patients with chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation (MV). We conducted a study using prospectively collected data in a cohort of patients with COPD requiring invasive MV to identify variables associated with extubation failure. Use of noninvasive or invasive MV within 48 hours after extubation was defined as extubation failure. A total of 148 patients with COPD were studied. Extubation failure occurred in 35% of studied patients. Using multiple regression analysis, independent predictors of extubation failure were physiologic abnormalities measured by Simplified Acute Physiology Score II above 35 on intensive care unit (ICU) admission (odds ratio [OR], 3.88; 95% confidence interval [CI], 1.65-9.12), home noninvasive MV (OR, 12.99; 95% CI, 2.86-58.89), and sterile endotracheal aspirations on the day of extubation were predictors of success (OR, 0.23; 95% CI, 0.10-0.52). Despite high rate of extubation failure, survival to ICU discharge was 91% of the studied population. Extubation failure in patients with COPD remains high despite a successful spontaneous breathing on T piece. Simplified Acute Physiology Score II at ICU admission, home noninvasive MV, and isolated pathogens on quantitative cultures of tracheobronchial secretions within 72 hours preceding extubation were predictors of extubation failure in the study population.

APACHE↗

PubMed2005

Antibacterial properties of some plants used in Mexican traditional medicine for the treatment of gastrointestinal disorders.

Antibacterial properties of aqueous and methanolic extracts of 26 medicinal plants used in Mexico to treat gastrointestinal disorders were tested against eight different species of enteropathogens: two Escherichia coli species; two Shigella sonnei species; two Shigella flexneri species; and two Salmonella sp. species. The results showed that all crude extracts exhibited antibacterial activity, at least against one of the microorganisms tested, at concentrations of 8 mg/mL or lower. The extracts from Caesalpinia pulcherria, Chiranthodendron pentadactylon, Cocos nucifera, Geranium mexicanum (aerial parts and roots), Hippocratea excelsa, and Punica granatum possessed strong antibacterial activity against most of the pathogens tested. In general, methanolic extracts were more active than aqueous extracts. Their activity was higher than chloramphenicol but did not exceed that of trimethoprim. Shigella sonnei species showed the highest susceptibility to both extracts. This is the first evaluation of these plants against bacterial pathogen isolates, which cause diarrhea and dysentery in Mexican population.

Animals↗

PubMed2004

Catheter-related bloodstream infection in adult haematology patients: catheter removal practice and outcome.

The aim of the present study was to describe the practice of central venous catheter (CVC) removal and outcomes of catheter-related bloodstream infection (CR-BSI) in adult haematology patients. Patients were identified retrospectively according to diagnosis coding of inpatient episodes and evaluated when, on examination of medical records, there had been evidence of sepsis with strong clinical suspicion that the source was the CVC. Demographic and bacteriological data, as well as therapeutic measures and clinical outcomes, were recorded. One hundred and three patient episodes were evaluated. The most frequent type of CVC was the Hickman catheter and the most frequently isolated pathogen was coagulase-negative staphylococci. Twenty-five percent of episodes were managed with catheter removal. Treatment failure, defined as recurrence of infection within 90 days or mortality attributed to sepsis within 30 days, occurred significantly more frequently in the group managed without catheter removal (52.5% versus 4%, P < 0.05). Specifically, 90-day recurrence was more common when the catheter was retained (46% versus 0%). However the difference in 30-day attributable mortality (7% versus 4%) was not significantly different. Notably, no significant difference between the two groups emerged in respect of other measured characteristics that had been considered as potential determinants of outcome. More frequent CVC removal for CR-BSI, in this population, should be considered. Management of CR-BSI without catheter removal is associated with treatment failure, morbidity and carries significant resource implications.

Adolescent↗

PubMed2006

Kinetic study of cytokines production by human peripheral blood mononuclear cells in response to Brucella DNA.

In spite of reports on cytokines induction by the Brucella DNA in murine model, there is no comparison between pathogenic and appropriate vaccine strains in human. We investigated the cytokines profile of human peripheral blood mononuclear cells (PBMCs) induced by DNA extracted from pathogenic isolates of Brucella melitensis and B. abortus as well as Rev1 and S19; the appropriate vaccine strains. It was observed that despite differential induction of Interleukin(IL)-12 and IL-10 production, identical IL-12/IL-10 concentration ratio was obtained by all Brucella strains DNAs that was 2 after 24 h and 4 after 5 days of incubation. In addition, IL-2 and Interferon(IFN)-gamma production were profoundly increased compared to the medium at day 3 and 5 respectively but IFN-alpha was not induced. Therefore, Brucella strains DNAs are Th1 inducing component with similar pattern in human PBMCs.

Blood↗

PubMed2006

Spectrum of fungal keratitis in north China.

PURPOSE: To report the epidemiological features, laboratory findings, and treatment outcomes in patients with fungal keratitis in north China. DESIGN: Retrospective hospital-based study. PARTICIPANTS: A total of 654 patients diagnosed with fungal keratitis at the Shandong Eye Institute from January 1999 to December 2004. METHODS: The medical records of 654 inpatients (654 eyes) with fungal keratitis were reviewed retrospectively for demographic features, risk factors, seasonal variation, clinical characteristics, laboratory findings, and treatment strategy. MAIN OUTCOME MEASURES: Patient history, ocular examination findings by slit-lamp biomicroscopy, laboratory findings from direct smear examination and fungal culture, and treatment protocol. RESULTS: Fungal keratitis constituted 61.9% of cases of severe infective keratitis among the inpatients at the Shandong Eye Institute during the 6 years. Males (60.6%) were more likely to be affected by fungal keratitis than females (39.4%). Almost one third of the patients (203) were middle aged (41-50 years old). Corneal trauma (51.4%), especially injury from plants (25.7% in all patients), was the most commonly associated risk factor. The incidence of fungal keratitis was higher in harvest seasons, including summer and autumn. An increasing tendency of incidence was noted in more recent years. Direct microscopic examination of the corneal scraping samples stained with potassium hydroxide showed positivity in 88.7% of the eyes. The fungal isolates were of Fusarium species in 437 eyes (73.3%) and Aspergillus species in 72 eyes (12.1%). Surgical interventions were performed in 604 eyes (92.4%), including therapeutic penetrating keratoplasty in 399 eyes (66.0%) and therapeutic lamellar keratoplasty (LK) in 177 eyes (29.3%). Globe integrity was preserved in 626 eyes (95.7%). CONCLUSIONS: With Fusarium species being the most commonly isolated pathogens, fungal keratitis is the leading cause of severe infective corneal ulcers in north China. Direct microscopic examination with potassium hydroxide wet mounts proves to be a rapid, simple, inexpensive diagnostic means. Corneal transplantation continues to be the most effective approach for the treatment of severe fungal keratitis. Early surgery, especially LK, can be considered if aggressive topical therapy does not achieve early disease control.

Adolescent↗

PubMed2004

Bactericidal activity of antimicrobial coated polyurethane sleeves for external fixation pins.

This study was conducted to assess the potential of gentamicin coated polyurethane sleeves to inhibit bacterial colonization on external fixation pins and wires. These antimicrobial sleeves have been designed to be fitted over the pins and wires, at the time of surgery, as a prophylactic approach to combat the major complication of external fixation treatment, pin tract infection. Elution testing was conducted to estimate the amount of gentamicin released into the pin tract. These gentamicin concentrations were compared to the gentamicin minimal inhibitory concentration (MIC) level for common pin tract pathogens. Elution testing revealed that the gentamicin coated polyurethane sleeves released significant quantities of the antibiotic for up to 26 weeks. The initial bolus release was characterized by predicted pin tract gentamicin concentrations of >80 microg/ml at the 2 h and 1 day elution time points. These amounts of gentamicin, delivered directly to the pin tract, are far beyond those that could be achieved via oral or intravenous administration. Furthermore, the expected concentration of gentamicin in the pin tract remained above the National Committee for Clinical Laboratory Standards (NCCLS) MIC breakpoint of 4 microg/ml, [Performance standards for antimicrobial susceptibility testing: twelfth informational supplement M100-S12, NCCLS, Wayne, PA, 2002], for at least 20 weeks. Data from the SENTRY antimicrobial surveillance program (1997-2002) established a high level of bactericidal activity for gentamicin, with 83.1% of the common pin tract pathogen isolates found to be susceptible to the antibiotic. The initial burst and subsequent long-term sustained local delivery of effective amounts of gentamicin from the antimicrobial sleeves would be expected to inhibit bacterial colonization on external fixation pins and wires. This inhibition of bacterial colonization should substantially reduce the incidence of pin tract infection, and improve the overall outcome and cost effectiveness of external fixation fracture management.

Bacteria↗

PubMed2006

Ophiobolin E and 8-epi-ophiobolin J produced by Drechslera gigantea, a potential mycoherbicide of weedy grasses.

Drechslera gigantea, a fungal pathogen isolated from large crabgrass (Digitaria sanguinalis) and proposed as a potential mycoherbicide of grass weeds, produces phytotoxic metabolites in liquid and solid cultures. Ophiobolin A and three minor ophiobolins i.e., 6-epi-ophiobolin A, 3-anhydro-6-epi-ophiobolin A and ophiobolin I were obtained from the liquid culture broths. Interestingly and unexpectedly, ophiobolins also appeared in cultures of this fungus and they were isolated together with the known ophiobolins B and J, and designed as ophiobolin E and 8-epi-ophiobolin J. They were characterized using essentially spectroscopic methods. It is noteworthy that D. gigantea produces such a plethora of bioactive organic substances. Some structure-activity relationship results are also discussed in this report.

Ascomycota↗

PubMed2006

[History of vaccination: from empiricism towards recombinant vaccines].

PURPOSE: Two hundreds years after the discovery of the smallpox vaccine, immunization remains one of the most powerful tools of preventive medicine. CURRENT KNOWLEDGE AND KEY POINTS: Immunization was born with Jenner, then Pasteur and expanded during the 19th and 20th century. It started with the empirical observation of cross-immunity between two diseases, cowpox and smallpox. It became a real science, with pathogen isolation, culture and attenuation or inactivation, to prepare a vaccine. Together with clinical and biological efficacy studies and adverse events assessments, it constructed the concept of "vaccinology". Protein conjugation of polyosidic vaccines has made possible early immunisation of infants. Nowadays, recombinant, reassortant, or virus-like particles technologies open the road for new vaccines. FUTURE PROSPECTS: Ongoing research opens the way for the development of new vaccines that will help to control transmittable diseases for which we are lacking antimicrobial agents.

Empirical Research↗

PubMed2005

Prospective interventional study to evaluate the efficacy and safety of liposomal amphotericin B as prophylaxis of fungal infections in high-risk liver transplant recipients.

INTRODUCTION: Invasive fungal infections are a life-threatening complication in transplant recipients. The prevalence of fungal infection after orthotopic liver transplantation (OLT) is 5% to 42%. The most common isolated pathogens are Candida and Aspergillus species. High-risk liver transplant recipients are more susceptible to the development of invasive fungal infections, with prevalence >40% and mortality rates of 78% to 100%. The strategy for fungal prophylaxis in this population has not been defined. PATIENTS AND METHODS: Among 100 consecutive OLT followed for 28 months, 21 recipients (15 men, overall mean age of 48.5 years, range 23-65 years) were considered to be high risk for the development of fungal infections when they presented at least one of the following criteria: acute liver failure, assisted ventilation >7 days, retransplantation, relaparotomy, antibiotic therapy >14 days, transfusion requirements >20 red blood cells units, and/or biliary leakage. This group received intravenous liposomal amphotericin B (1 mg/kg/d for 7-10 days). RESULTS: One-year survival in the high-risk group was 80%. Prevalence of invasive fungal infection was 9.5%. No Candida infection was observed. Two patients developed Aspergillus infection: an abdominal aspergillosis treated with percutaneous drainage and liposomal amphotericin B (5 mg/kg/d) showed a favorable clinical outcome. The other patient who developed brain aspergillosis died 25 days after OLT. Adverse events related to the drug were hypokalemia (n = 2), back pain (n = 3), and renal dysfunction (n = 2). None of these events required withdrawal of the prophylaxis regimen. CONCLUSION: In our series, prophylaxis with liposomal amphotericin B in high-risk liver graft recipients showed a low rate of severe fungal infections. More studies are needed in order to determine the highest risk population and the best drug dosage.

Amphotericin B↗

PubMed2004

Rationale for the development of immunotherapy regimens against enterococcal infections.

Enterococci are the third most common pathogen isolated in bloodstream infections. Increasing resistance against multiple antimicrobial agents has left few treatment options for enterococcal infections, and alternative therapeutic approaches are needed. Although a variety of virulence factors have been described for Enterococcus faecalis, only aggregation substance (AS) and a teichoic acid-like capsular polysaccharide have been evaluated for their potential for vaccine development. Antibodies raised against purified capsular polysaccharide are highly opsonic and protect mice against bacteremia after active and passive immunization. Since E. faecalis expresses only a limited number of capsular serotypes, this antigen may be an attractive candidate for development of a conjugate vaccine.

Antigens, Bacterial↗

PubMed2004

Antimicrobial susceptibility of mastitis pathogens from first lactation and older cows.

Increasing antimicrobial resistance has become a serious concern worldwide and antimicrobial use in animal agriculture is currently under scrutiny. Mastitis is the most common reason for antibiotic use in dairy herds and thus, antimicrobial resistance of mastitis pathogens has received recent attention. The purpose of this study was to describe and compare antimicrobial susceptibility of mastitis pathogens isolated at calving from first lactation and older cows. A total of 202 bacteria were isolated from intramammary infections (IMIs) within 3 days after calving over a 16-month study period in the Krauss Dairy Research Herd at the Ohio Agricultural Research and Development Center (OARDC) in Wooster, OH. Of these IMIs, 78% were caused by coagulase-negative staphylococci (CNS). Forty-four percent of them were resistant to at least one antibiotic. Most resistance was observed against penicillin, 39% of the isolates from older cows and 26% from first lactation cows being resistant to penicillin (P > 0.05). Also MIC90 for penicillin was higher among isolates from older cows. On the other hand, resistance to tetracycline was more common and MIC90 higher among isolates from first lactation cows than from older cows. Differences in the proportions of resistant isolates between first lactation and older cows were not statistically significant, though. The resistance patterns of the CNS isolated during the study are concordant with antimicrobial usage in the study herd. This is in agreement with the generally accepted notion that selection pressure from the use of antibiotics is a main factor in development of antibiotic resistance.

Animals↗

PubMed2004

Expansion of quasispecies diversity but no evidence for adaptive evolution of SHIV during rapid serial transfers among seronegative macaques.

Four successive, rapid serial passages of the nonpathogenic, CCR5-tropic simian-human immunodeficiency virus SHIV(SF162) in rhesus macaques resulted in an increase in acute plasma viremia with each passage and the emergence of a pathogenic isolate SHIV(SF162P3) in one of the passage three transfer animals (macaque T353). To explore the mechanism(s) underlying increased virulence of SHIV(SF162) upon in vivo passage, the evolution of the HIV-1 envelope gene was characterized in plasma and PBMC samples obtained from animals before (week 1) and after (week 3) the time of virus transfer. We found no evidence in support of adaptive evolution of the HIV gp120 during rapid serial passage; however, the animals which later received passage virus had more diverse quasispecies. SHIV(SF162P3)-like gp120 sequences were first detected in macaque T353 at week 6, after seroconversion. These sequence changes increased in frequency and number at later time points. The first sequence change conferred neutralization escape but not an increase in viral infectivity that could account for the apparent increase in replicative capacity of the later passage viruses. Collectively, our data argue against any host-specific adaptation of the HIV-1 envelope gp120 as the basis for the generation of more aggressive SHIV variants during rapid serial transfers in seronegative macaques, and support the model of quasispecies diversity as a predictor of pathogenesis. Envelope sequence changes accumulate principally in response to immune pressure exerted by the host, generating viral variants that can persist in the presence of a strong host immune response.

Amino Acid Sequence↗

PubMed2006

[Acute mastoiditis in children. A retrospective study and literature review].

OBJECTIVE: To review our experience and results in the diagnosis and treatment of acute mastoiditis, a pathology with an increasing incidence in the recent years. METHODS: The study reviewed 49 pediatric patients diagnosed and treated of acute mastoiditis between 1994 and 2003 in our hospital. We summarize epidemiologic, laboratory and clinical features. RESULTS: The mean age was 2.5 years. Seventy-five percent of cases were in autumn and winter months and nearly twenty-five percent had been diagnosed in the last year. S. pneumoniae was the most commonly isolated pathogen (28.6%), although a sterile result was the most frequent (38.1%). Twenty-four patients (48.9%) required surgical treatment. Only five patients (10.2%) developed complications. CONCLUSIONS: Acute mastoiditis is a pathology with an important incidence and is generally the consequence of an untreated otitis or an insufficient treatment. Due to the low number of complications, we can not estimate through statistical analysis valid markers like predictors for complication.

Acute Disease↗

PubMed1988

Results of noncomparative studies of cefotetan in the treatment of obstetric and gynecologic infections.

In a multicenter trial involving 11 centers, 160 women were enrolled to evaluate the safety and effectiveness of 1 or 2 gm of cefotetan administered every 12 hours in the treatment of obstetric and gynecologic infections. The 133 evaluable patients generally were under 25 years of age, were nonwhite, and had hospital-acquired endometritis or pelvic inflammatory disease caused by both aerobic and anaerobic bacteria. Escherichia coli, Neisseria gonorrhoeae, group D streptococci, Bacteroides sp., and Peptococcus sp. were among the most frequently isolated pathogens. The patients were treated for a mean of 5.6 +/- 1.6 days and received a total dose of 19.27 gm. The signs and symptoms of infection were cleared or improved in 93% of the 133 patients evaluable for clinical response. Of the 116 evaluated bacteriologically, 95% had a satisfactory or presumed satisfactory response; only six patients (5%) were considered to be bacteriologic failures. Differences in the results of several clinical laboratory tests performed before and after treatment were statistically, but not clinically, significant (p less than 0.05). Safety was evaluated in the 158 patients who received cefotetan, and only four (3%) had adverse reactions considered related to the drug. Cefotetan was clearly effective and produced no untoward reactions in these women with obstetric and gynecologic infections caused by both aerobic and anaerobic organisms when administered at 1 or 2 gm every 12 hours.

Adult↗

PubMed1996

The pathogenesis of Staphylococcus aureus in the trauma patient and potential future therapies.

BACKGROUND: Staphylococcus aureus is the most frequently isolated pathogen in the trauma patient and uses multiple virulent factors to cause infection. At the cellular level, infection begins with the prokaryotic bacterial cell manipulating the eukaryotic host cell through its virulent factors. Researching this cellular interaction by describing the mechanisms of actions of various virulent factors may lead to new preventive therapies which will make the trauma patient less susceptible to S aureus infections. METHODS: Surgical, medical, and microbial literature was reviewed to provide an update on S aureus pathogenesis. RESULTS: Novel future therapies, in addition to antibiotics, are being devised based on understanding the molecular nature of S aureus pathogenesis. CONCLUSION: The impact of S aureus on trauma will increase as S aureus develops more antibiotic resistance and as the trauma population becomes older and includes an increasing proportion of immunocompromised patients. To meet the challenge of increased virulence, trauma surgeons should be directly involved in the research of microbial pathogenesis.

Bacterial Adhesion↗

PubMed2001

Evolution and function of the neisserial dam-replacing gene.

Phase variation through slippage-like mechanisms involving homopolymeric tracts depends in part on the absence of Dam-methylase in several pathogenic isolates of Neisseria meningitidis. In Dam-defective strains drg (dam-replacing gene), flanked by pseudo-transposable small repeated elements (SREs), replaced dam. We demonstrate that drg encodes a restriction endonuclease (NmeBII) that cleaves 5'-GmeATC-3'. drg is also present in 50% of Neisseria lactamica strains, but in most of them it is inactive because of the absence of an SRE-providing promoter. This is associated with the presence of GATmeC, suggesting an alternative restriction-modification system (RM) specific for 5'-GATC-3', similar to Sau3AI-RM of Staphylococcus aureus 3A, Lactococcus lactis KR2 and Listeria monocytogenes.

Bacterial Proteins↗

PubMed1993

Single-dose pharmacokinetics and safety of HA-1A, a human IgM anti-lipid-A monoclonal antibody, in pediatric patients with sepsis syndrome.

The pharmacokinetics and safety of HA-1A (Nebacumab), a human IgM monoclonal antibody with specificity for the lipid A region of endotoxin, were evaluated in a multicenter trial of pediatric patients with sepsis syndrome or septic shock. Forty-two patients received a total of 44 infusions of drug, at a dose of 3 mg/kg (maximum 100 mg). The mean age was 7 years 10 months (range, 11 months to 16 years 7 months). The pharmacokinetic behavior of HA-1A during 36 hours was best described by a one-compartment open model. Clearance (6.1 +/- 2.0 ml/kg per hour) and apparent volume of distribution at steady state (0.11 +/- 0.03 L/kg) were larger than values reported previously in adults with sepsis syndrome. Elimination half-life (14.5 +/- 6.8 hours) and plasma concentration after infusion (30.7 +/- 14.5 mg/L) were similar to adults' values. In an additional three patients studied for 72 hours after administration, a biexponential function (i.e., two-compartment open model) best described the pharmacokinetic behavior of HA-1A: clearance (1.5 +/- 1.4 ml/hr per kilogram) and apparent volume of distribution at steady state (0.2 +/- 0.02 L/kg) were different (p < 0.002) from values observed in children's blood samples during 36 hours. Within the pediatric population, no age-related differences in pharmacokinetics could be detected. Drug disposition was unaffected by renal or hepatic dysfunction. Decreased blood pressure was the most frequently reported adverse event; 4 (9%) episodes in 44 infusions were considered possibly related to the study drug. Gram-negative bacteremia was documented in 23 (55%) of 42 patients. The overall mortality rate was 31%. Enterobacter cloacae was the most common pathogen isolated. Haemophilus influenzae type b was isolated from one child with sepsis syndrome. We conclude that infusion of HA-1A in children is associated with a low incidence of side effects. The pharmacokinetic-pharmacodynamic behavior of HA-1A in children requires further study to determine whether developmental differences exist and how these differences might affect drug administration. Efficacy remains to be studied.

Adolescent↗

PubMed1998

Nitrofurantoin prophylaxis for bacteriuria and urinary tract infection in children with neurogenic bladder on intermittent catheterization.

OBJECTIVE: To determine the effect of nitrofurantoin prophylaxis on rates of bacteriuria and symptomatic urinary tract infection in children with chronic neurogenic bladder receiving clean intermittent catheterization. DESIGN: Double-blind, placebo-controlled, crossover trial of 15 children receiving nitrofurantoin or placebo for 11 months (5 months receiving one drug, then 1 month of washout followed by 5 months of the alternate drug). Weekly home visits were made. During each visit a sample of bladder urine was obtained by intermittent catheterization, signs and symptoms of urinary tract infection were recorded, and all medications were recorded as well as a capsule count of the study drug. RESULTS: During nitrofurantoin the frequency of bacteriuria remained high. Cultures of 74% (203 of 274) of the 274 samples on placebo were positive for a pathogen (> or = 10(4) colony-forming units per milliliter) compared with 65% (165 of 252) of the 252 samples on nitrofurantoin. The bacterial species responsible for bacteriuria, however, were altered; Escherichia coli, the most common pathogen isolated during placebo, was replaced by resistant Klebsiella spp. and Pseudomonas spp. during nitrofurantoin. The carriage of these resistant organisms tripled during nitrofurantoin. Symptomatic infection dropped in half on nitrofurantoin, but this decline was due solely to infections caused by E. coli. Despite an increased frequency of resistant organisms on nitrofurantoin prophylaxis, an increase in urinary tract infections caused by these resistant organisms did not occur. CONCLUSION: Routine use of nitrofurantoin prophylaxis in an attempt to eradicate bacteriuria in patients with chronic neurogenic bladder is not effective.

Adolescent↗