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PubMed2007

Clinical and hemostatic responses to treatment in ventilator-associated pneumonia: role of bacterial pathogens.

OBJECTIVE: To determine pathogen-specific kinetic changes in the alveolar procoagulant (PC) activity, tissue factor (TF), and tissue factor pathway inhibitor (TFPI) expression during the course of ventilator-associated pneumonia (VAP) and to assess the relationship between clinical resolution, intra-alveolar bacterial eradication, and restoration of hemostatic balance. DESIGN: Prospective, multiple-center study in a cohort of VAP patients. SETTING: Two university-affiliated intensive care units. PATIENTS: Thirty-five patients with microbiologically documented VAP who received adequate antimicrobial coverage and 13 controls. INTERVENTIONS: Nonbronchoscopic bronchoalveolar lavage was performed at the onset of VAP and on days 4 and 8 after initiation of antibiotic therapy. Samples were assayed for PC, TF, TFPI, and thrombin-antithrombin complex (TATc). The corresponding Clinical Pulmonary Infection Score (CPIS) was collected simultaneously. MEASUREMENTS AND MAIN RESULTS: Isolated pathogens included Pseudomonas aeruginosa (n=13), methicillin-resistant Staphylococcus aureus (MRSA) (n=8), methicillin-sensitive S. aureus (MSSA) (n=7), and Escherichia coli (n=7). Although PC activity and TF were increased among the various pathogens at the onset of VAP, the levels of those with P. aeruginosa remained elevated at the end of treatment compared with controls and other etiological agents. TFPI levels were elevated for the duration of the study for all pathogens. A universal increase in TATc was noted at the onset of VAP, but the difference among the group of pathogens was significant at days 4 and 8 posttherapy. Despite the persisting hemostatic imbalance and incomplete intra-alveolar eradication of P. aeruginosa at end of therapy, the CPIS fell comparably at each time point irrespective of the etiological agents. CONCLUSIONS: Alveolar activation of the TF-dependent pathway may be species-specific in VAP and may not be adequately balanced by TFPI. The disparity between clinical response and eradication of P. aeruginosa from the intra-alveolar space suggests the need for biological markers to guide response to therapy.

Aged↗
PubMed1993

Vaginitis due to Saccharomyces cerevisiae: epidemiology, clinical aspects, and therapy.

Vaginitis due to Saccharomyces species is extremely rare. Nine patients with 20 vaginal isolates of Saccharomyces cerevisiae who presented with either asymptomatic vaginal colonization or symptomatic vaginitis indistinguishable from that caused by Candida albicans are described. All patients had a history of chronic or recurrent vaginitis, and all but two had systemic or local predisposing factors. In vitro tests of antimycotic sensitivity revealed reduced susceptibility of S. cerevisiae to the majority of available azole agents, with outright resistance to fluconazole. In accordance with these findings, the clinical response to conventional topical and oral antimycotic drugs was frequently suboptimal and incomplete. Electrophoretic karyotyping of strains revealed several distinct types of S. cerevisiae; this information permitted both longitudinal follow-up and differentiation of relapse from reinfection. In three patients with recurrent vaginitis, a unique epidemiological relationship was documented between S. cerevisiae and Torulopsis glabrata, another unusual and resistant vaginal pathogen. Isolation of S. cerevisiae from the vagina of symptomatic patients should not be ignored; treatment of vaginal infection with this yeast requires selected, often prolonged therapy.

Adult↗
PubMed2005

Linezolid in the treatment of Gram-positive prosthetic joint infections.

OBJECTIVES: To investigate the clinical efficacy and safety of linezolid in the treatment of Gram-positive prosthetic hip and knee infections. MATERIALS AND METHODS: A retrospective evaluation of patients hospitalized in the Department of Infectious Diseases of San Martino Hospital in Genoa with the diagnosis of Gram-positive prosthetic joint infection and treated with intravenous and/or oral linezolid. Primary end points were the patient clinical outcome at the end of treatment and at long-term follow-up (up to 12 months after the end of treatment). RESULTS: Between May 1999 and September 2003, 20 patients with prosthetic joint infection were treated with linezolid. Pathogens isolated were: methicillin-resistant Staphylococcus aureus (MRSA), 14 strains; methicillin-resistant coagulase-negative staphylococci, five strains; and Enterococcus spp., one strain. The overall duration of treatment was 7.2 +/- 2 weeks (range 6-10 weeks). Patients were given intravenous therapy for 3-7 days as inpatients, then were changed as outpatients to oral therapy under weekly laboratory testing. At long-term follow-up (1 year), we observed four cases of failure due to relapsing infections. The other 16 patients treated with linezolid did not need further surgical substitution of prosthesis or surgical joint revision. Linezolid was well tolerated, and no drug-related events leading to discontinuation of treatment were recorded. CONCLUSIONS: Our data indicate that linezolid may be an effective alternative therapy for orthopaedic infections caused by Gram-positive resistant pathogens and that a prospective and comparative evaluation of linezolid in this setting is necessary.

Acetamides↗
PubMed2000

Rapid identification of bacteria from positive blood cultures by fluorescence-based PCR-single-strand conformation polymorphism analysis of the 16S rRNA gene.

Bacteremia continues to result in significant morbidity and mortality, particularly in patients who are immunocompromised. Currently, patients with suspected bacteremia are empirically administered broad-spectrum antibiotics, as definitive diagnosis relies upon the use of blood cultures, which impose significant delays in and limitations to pathogen identification. To address the limitations of growth-based identification, the sequence variability of the 16S rRNA gene of bacteria was targeted for rapid identification of bacterial pathogens isolated directly from blood cultures using a fluorescence-based PCR-single-strand conformation polymorphism (SSCP) protocol. Species-specific SSCP patterns were determined for 25 of the most common bacterial species isolated from blood cultures; these isolates subsequently served as a reference collection for bacterial identification for new cases of bacteremia. A total of 272 blood-culture-positive patient specimens containing bacteria were tested. A previously determined SSCP pattern was observed for 251 (92%) specimens, with 21 (8%) specimens demonstrating SSCP patterns distinct from those in the reference collection. Time to identification from blood culture positivity ranged from 1 to 8 days with biochemical testing, whereas identification by fluorescence-based capillary electrophoresis was obtained as early as 7 h at a calculated cost of $10 (U.S. currency) per specimen when tested in batches of 10. Limitations encountered included the inability to consistently detect mixed cultures as well as some species demonstrating identical SSCP patterns. This method can be applied directly to blood cultures or whole-blood specimens, where early pathogen identification would result in a timely diagnosis with possible implications for patient management costs and the mortality and morbidity of infections.

Bacteremia↗
PubMed2005

Characteristics of primary osteomyelitis among children in a medical center in Taipei, 1984-2002.

BACKGROUND AND PURPOSE: The presentation and sequelae of osteomyelitis are variable. This study evaluated the clinical manifestations and outcome of osteomyelitis in children in different age groups, and in different periods before and after the implementation of National Health Insurance (NHI). METHODS: The records of pediatric patients with osteomyelitis treated at a medical center in Taipei from 1984 to 2002 were reviewed. Clinical features, pathogens, laboratory and imaging findings, treatment, and outcome were analyzed. The patients were stratified into 3 groups based on age: infants (< or = 3 months of age), young children (between 4 months and 5 years), and older children and adolescents (> 5 years). Based on the date of implementation of the NHI program, the study period was divided into 2 stages: prior to implementation, from January 1984 to February 1995; and after implementation, from March 1995 to December 2002. RESULTS: The records of 209 patients were reviewed, including 45 infants, 77 young children, and 87 older children. The most common presenting findings were local tenderness (79%), local swelling (72%), and fever (57%). The lower limbs were the most commonly involved sites (65%). Staphylococcus aureus (34%), Mycobacterium tuberculosis (10%), Salmonella species (7%), and Pseudomonas aeruginosa (6%) were the most frequently isolated pathogens. At the time of diagnosis, abnormalities were found on radiographs in 83% of patients and on radionuclide bone scans in 86%. Surgical intervention with local debridement and curettage was performed in 102 patients (49%). Sixty five patients (31%) developed complications, including specific bony sequelae in 26 (12%). Sepsis and septic arthritis were more common in infants (p < 0.01). A history of trauma, protracted course of osteomyelitis, and surgical intervention were more common in older children and adolescents (p < 0.01). After the implementation of NHI, a larger proportion of patients had negative cultures (p < 0.01), and the mean duration of antibiotic therapy was shorter (p = 0.01). CONCLUSIONS: The clinical characteristics of osteomyelitis associated with sepsis or septic arthritis, chronic changes, and the need for surgery may differ depending on the age of the child. S. aureus, M. tuberculosis, and salmonellae were the most common pathogens in this Taiwanese series. Implementation of NHI in the more recent decade of the study period was associated with a shorter duration of intravenous antibiotic administration.

Adolescent↗
PubMed1999

Impact of simple screening criteria on utilization of low-yield bacterial stool cultures in a Children's Hospital.

OBJECTIVE: To determine diagnostic yield of stool cultures for Salmonella, Shigella, Campylobacter jejuni, Yersinia enterocolitica, and Escherichia coli O157:H7 (SSCYE) among hospitalized children and to develop guidelines for appropriate use of these tests. Setting. Tertiary care pediatric hospital. DESIGN: Computerized records from the Microbiology Laboratory from January 1992 to December 1996 were reviewed retrospectively to collect data on the number of stool cultures performed in inpatients and outpatients, the length of hospital stay at the time cultures were sent, and diagnostic yield of cultures in hospitalized patients. A detailed review of medical records of all patients with a stool pathogen isolated after 3 days of hospitalization was also undertaken. The results from this retrospective analysis were used to develop guidelines to reduce unwarranted stool cultures and to educate medical care providers in the appropriate use of these tests. The impact of these guidelines on reduction in the volume of stool cultures performed on hospitalized patients was measured prospectively from January 1998 to June 1998. RESULTS: A total of 27 110 stool cultures for SSCYE were performed in the 5-year study period. Of the 14 125 cultures from inpatients, 174 (1.2%) were positive. Among the cultures from inpatients, 9378 (66%) were from patients hospitalized for >3 days. Only 13 (.14%) were positive. Of these 13 cultures, 4 represented nosocomial infections, whereas the remaining 9 cultures either were sent to document clearance from a patient known previously to be infected with an enteric pathogen (7), or were attributed to delayed testing in individuals admitted with a diarrheal illness (2). Introduction of guidelines to reject all SSCYE cultures from patients hospitalized for >3 days who did not meet specified criteria was associated with an overall reduction of 689 (43%) in the volume of tests performed in the 6-month period evaluated. This included 497 fewer cultures ordered and 192 cultures that were ordered but rejected because screening criteria were not met. Only 11 (5.4%) of 203 cultures sent >3 days after admission were processed because they met clinical criteria for testing. None were positive. Estimated cost savings were $50 163/year. CONCLUSIONS: Stool cultures for SSCYE among hospitalized patients have very low diagnostic yield and are extremely overutilized. Simple guidelines, such as rejecting (with few exceptions) cultures from patients hospitalized for >3 days, can reduce substantially such unnecessary testing.

Boston↗
PubMedDate not supplied

In-vitro susceptibility patterns of some major respiratory tract pathogens in Nigeria to eleven selected antibiotics.

A study of the antibiotic sensitivity patterns of nine pathogens isolated from bronchopulmonary infections was made using the disc diffusion method. Erythromycin, carbenicillin and chloramphenicol were in that sequence the drugs most effective against the Gram-positive cocci, followed by ampicillin to which however, 56% of the strains of staphylococcus aureus tested showed resistance. More than 95% of the strains of Haemophilus influenza were very susceptible to carbenicillin and chloramphenicol while over 70% were sensitive to ampicillin, penicillin G, and erythromycin. All strains of Pseudomonas aeruginosa tested were sensitive to carbenicillin and gentamicin. Klebsiella pneumoniae was moderately sensitive to tetracycline, carbenicillin, streptomycin, gentamicin and septrin (co-trimoxazole). Sixty-seven percent of Escherichia coli were sensitive to septrin while 50% were susceptible to chloramphenicol, erythromycin and ampicillin. In general there was evidence that tetracycline, septrin, penicillin G, streptomycin and orbenin had become less effective against most of the respiratory tract pathogens. The study shows the necessity for the early identification of the aetiologic agents and their antibiotic sensitivity patterns so as to reduce the degree of wasteful polypharmacy or the development of high resistance rates in hospitals and their environments.

Anti-Bacterial Agents↗
PubMed2005

Trends in antibiotic resistance of respiratory tract pathogens in children in Geneva, Switzerland.

UNLABELLED: Bacteria increasingly resistant to antibiotics are a major treatment concern of respiratory tract pathogens in children. The aim of this study was to assess the trends of resistance of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis to several classes of antibiotics in children<16 years of age and to compare its prevalence with surrounding countries. We studied retrospectively the susceptibility of respiratory tract pathogens isolated from specimens collected from patients at the Geneva Children's Hospital between 1989 and 2004. The susceptibility of S. pneumoniae to penicillin decreased from 98% to 58% (P<0.001) within 16 years, mainly due to strains intermediately resistant (MICs 0.12-1.0 microg/ml). Also erythromycin-susceptible pneumococci decreased from 97% to 63% (P<0.001). The susceptibility of H. influenzae to amoxicillin also significantly declined (87% vs. 82%, P<0.001), and the susceptibility of M. catarrhalis to this drug almost disappeared (29% vs. 5%, P<0.001). However, in 2004 these two bacteria remained 100% susceptible to amoxicillin-clavulanic acid, second and third generation cephalosporins. Invasive H. influenzae strains were significantly more resistant to ampicillin than non-invasive strains, but no susceptibility difference between invasive and non-invasive S. pneumoniae was determined. CONCLUSION: During the 16 years studied, the antibiotic resistance of respiratory tract pathogens steadily and significantly increased in children, especially S. pneumoniae. This situation in Geneva is similar to neighbouring France rather than to the rest of Switzerland. A permanent surveillance of microbial susceptibility to antibiotics is essential and a limitation of antibiotic prescription together with information of the judicious use may impede the actual resistance trend.

Child↗
PubMed2005

Both early-onset and late-onset ventilator-associated pneumonia are caused mainly by potentially multiresistant bacteria.

OBJECTIVE: To compare the causative pathogens of early-onset and late-onset ventilator-associated pneumonia (VAP) diagnosed by bronchoalveolar lavage quantitative cultures. Most previous reports have been based on endotracheal aspirate cultures and gave uncertain findings. DESIGN: Prospective evaluation of consecutive patients with clinical suspicion for VAP. SETTING: Multidisciplinary intensive care unit of a university hospital. PATIENTS AND PARTICIPANTS: During a 3-year period 473 patients with clinical suspicion of VAP entered the study. Diagnosis of VAP was confirmed by cultures of bronchoalveolar lavage (> 10(4) cfu/ml) specimens in 408 patients. INTERVENTIONS: Protected bronchoalveolar lavage samples were taken. Initial antibiotic therapy was modified upon bronchoalveolar lavage culture results. MEASUREMENTS AND RESULTS: Among 408 patients 191 had early-onset (< 7 days mechanical ventilation) and 217 late-onset (> or = 7 days) VAP. Potentially multiresistant bacteria, mainly Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA), were the most commonly isolated pathogens in both types of VAP. No difference was noted in the contribution of potentially multiresistant pathogens (79% vs. 85%), P. aeruginosa (42% vs. 47%), or MRSA (33% vs. 30%) between early-onset and late-onset VAP. Initial antibiotic therapy was modified in 58% of early-onset VAP episodes and in 36% of late-onset VAP episodes. No difference in mortality was found between the two types of VAP. CONCLUSIONS: Both early-onset and late-onset VAP were mainly caused by potentially multiresistant bacteria, most commonly P. aeruginosa and MRSA. Antimicrobial agents against these pathogens should be prescribed empirically, at least in our institution.

APACHE↗
PubMed1993

Pathogens and predictors of fatal septicemia associated with human immunodeficiency virus infection in Ivory Coast, west Africa.

In East Africa, bacteremia is more common in hospitalized human immunodeficiency virus (HIV) type 1-positive than -negative patients. In 1991, blood cultures and clinical and laboratory data were obtained from 319 patients in Ivory Coast, where both HIV-1 and -2 infections occur. Forty-three bacterial, 10 mycobacterial, and 8 fungal pathogens were isolated from blood of 54 patients (17%). Pathogens isolated significantly (P < or = .05) more frequently from HIV-positive than -negative patients were nonmycobacterial bacteria, particularly Salmonella enteritidis; mycobacteria, particularly Mycobacterium tuberculosis-Mycobacterium bovis; and yeast or fungus. HIV-1 or -2 positivity was associated with a 3-fold increased risk for septicemia (P < .02). HIV-positive patients with fever or with lymphocyte counts < 1000 were more likely to be septicemic than those without these characteristics. Mortality increased significantly with HIV positivity (40% vs. 14%, P < .001) and, among HIV-positive patients, with having pathogens isolated from blood (63% vs. 33%, P < .001).

Adult↗
PubMed1988

Fifteen-year experience with bloodstream isolates of coagulase-negative staphylococci in neonatal intensive care.

Investigators worldwide, as well as the neonatologists and infection control team at our hospital, have reported that the incidence of coagulase-negative staphylococcal bacteremia in critically ill neonates has increased dramatically in recent years. To investigate these claims, we examined the results of all blood cultures obtained from 1970 to 1984 in our neonatal intensive care unit. Throughout this study period, coagulase-negative staphylococci were prominent blood culture isolates (crude overall incidence of 4.4 positive bacteremia workups per 100 neonates admitted; range, 2.5 to 6.7), representing 26.3 to 69.6% of all positive cultures. There was no significant increase in incidence over time by analysis of linear trend. Detailed analysis of data from 1976 and 1982 (two selected years for which complete information concerning culturing practices and patient characteristics was available) revealed that these observations were not explained by changes in the frequency of blood culturing. In both 1976 and 1982, the probability that a blood culture would grow coagulase-negative staphylococci increased steadily from 2 to 3% shortly after admission to reach a level of about 12% in week 3 of hospitalization, before declining to an intermediate level thereafter. This pattern is more consistent with nosocomial bacteremia than with contamination of blood cultures. Contrary to clinical reports, coagulase-negative staphylococci have been the principal pathogens isolated from blood cultures in our neonatal intensive care unit since at least 1970, with no measurable increase over the subsequent 14 years.

Coagulase↗
PubMed2005

[In vitro activity of telithromycin against community acquired respiratory pathogens].

BACKGROUND: Telithromycin is a new ketolide antimicrobial, that can be useful for the treatment of respiratory infections. AIM: To compare in vitro activity of telithromycin against respiratory pathogens, isolated in outpatient clinics. MATERIAL AND METHODS: Two hundred eighty strains isolated from patients with respiratory infections, were studied. The strains studied were S pneumoniae, penicillin sensitive (SPNS:57); intermediate (SPNI:35), resistant (SPNR:25); S pyogenes (SP:57); H influenzae (HIN 51); M catarrhalis (MC:25) and S aureus meticillin sensitive (SAUS:30). Minimal inhibitory concentration (MIC) by broth microdilution was studied for telitrhomycin and levofloxacin in all strains. Other antimicrobials studied, but not in all strains were erythromycin, clindamycin, trimetoprim sulphamethoxazole, oxacillin, amoxicillin-clavulanic acid and cefuroxime. RESULTS: All strains were sensible to telithromycin at a concentration -4 microg/ml. MIC 90 and its range for SPNS was 0.03 microg/ml (-0.004-0.12), for SPNI was 0.03 microg/ml (-0.004-025), for SPNR was 0.06 microg/ml (-0.004-0.25), for HIN was 2 microg/ml (0.12-4), for SP was 0.5 microg/ml (-0.004-2), for MC was 0.5 microg/ml (0.06-2) and for SAU was 0.25 microg/ml (0.06-0.25). CONCLUSIONS: All studied pathogens were sensible to telithromycin in vitro. This antimicrobial is an alternative for the treatment of community acquired respiratory infections.

Anti-Bacterial Agents↗
PubMed2002

Porcine circovirus type 2 (PCV-2) coinfections in US field cases of postweaning multisystemic wasting syndrome (PMWS).

The prevalence of different pathogens detected in combination with porcine circovirus type 2 (PCV-2) was studied retrospectively in field cases of postweaning multisystemic wasting syndrome (PMWS) diagnosed at the Iowa State University Veterinary Diagnostic Laboratory, Ames, Iowa, between January 2000, and September 2001. The presence of PCV-2 antigen in lymphoid tissues and/or lung, demonstrated by immunohistochemistry, together with moderate to severe lymphoid depletion and/or granulomatous lymphadenitis, was used as the criteria for the diagnosis of PMWS. A total of 484 cases fulfilled these criteria. Most of the cases (294/369) of PMWS occurred in pigs between the ages of 8 and 18 weeks, with a peak at 10 weeks of age. Porcine reproductive and respiratory syndrome virus was detected in 51.9% of the cases, Mycoplasma hyopneumoniae in 35.5%, bacterial septicemia in 14.0%, bacterial pneumonia in 7.6%, swine influenza virus in 5.4%, and PCV-2 alone in 1.9%. In cases with bacterial septicemia the most frequently isolated pathogen was Streptococcus suis. In cases with bacterial pneumonia, Pasteurella multocida was the most prevalent.

Animals↗
PubMed2006

Extent of horizontal gene transfer in evolution of Streptococci of the salivarius group.

The phylogenetically closely related species Streptococcus salivarius and Streptococcus vestibularis are oral bacteria that are considered commensals, although they can also be found in human infections. The relationship between these two species and the relationship between strains isolated from carriers and strains responsible for invasive infections were investigated by multilocus sequence typing and additional sequence analysis. The clustering of several S. vestibularis alleles and the extent of genomic divergence at certain loci support the conclusion that S. salivarius and S. vestibularis are separate species. The level of sequence diversity in S. salivarius alleles is generally high, whereas that in S. vestibularis alleles is low at certain loci, indicating that the latter species might have evolved recently. Cluster analysis indicated that there has been genetic exchange between S. salivarius and S. vestibularis at three of the nine loci investigated. Horizontal gene transfer between streptococci belonging to the S. salivarius group and other oral streptococci was also detected at several loci. A high level of recombination in S. salivarius was revealed by allele index association and split decomposition sequence analyses. Commensal and infection-associated S. salivarius strains could not be distinguished by cluster analysis, suggesting that the pathogen isolates are opportunistic. Taken together, our results indicate that there is a high level of gene exchange that contributes to the evolution of two streptococcal species from the human oral cavity.

Base Sequence↗
PubMed2006

Antifungal efficacy of chitosan and its thiourea derivatives upon the growth of some sugar-beet pathogens.

Chitosan (CS) was modified by reaction with benzoyl thiocyanate to give a thiourea derivative (TUCS). The antifungal behavior of chitosan and its thiourea derivative was investigated in vitro on the mycelial growth, sporulation and germination of conidia or sclerotia of the following sugar-beet: Beta vulgaris pathogens isolated in Egypt, Rhizoctonia solani Kühn (AG(2-2)) Sclerotium rolfsii Sacc. and Fusarium solani (Mart.) Sacc. All the prepared thiourea derivatives had a significant inhibiting effect on the different stages of development on the germination of conidia or sclerotia of all the investigated fungi in the polymer concentration range of 5-1000 microg ml(-1). In the absence of chitosan and its derivative, R. solani exhibited the fastest growth of the fungi studied. However, growth tolerance of the modified chitosan was highest for F. solani and lowest for R. solani. The most sensitive to the modified chitosan stress with regard to their germination and number produced were the sclerotia of S. rolfsii. It has been found that the TUCS is a much better fungicidal agent (about 60 times more) than the pure CS against most of the fungal strains tested. The molecular weight and the degree of deacetylation were found to have an important effect on the growth activities of the pathogens.

Antifungal Agents↗
PubMedDate not supplied

Francisella tularensis proteome: low levels of ASB-14 facilitate the visualization of membrane proteins in total protein extracts.

Proteomic analysis of bacterial pathogens isolated from in vivo sources, such as infected tissues, provides many challenges not the least of which is the limited quantity of sample available for analysis. It is, therefore, highly desirable to develop a one-step cellular lysis and protein solubilization method that minimizes protein losses and allows the maximum possible coverage of the proteome. Here, we have used standard sample buffer constituents including urea, thiourea and DTT, but varied the detergent composition of the buffers in order to achieve the best quality of gels and the greatest spot resolution. We found that the most efficient solubilizing solution in this case consisted of 7 M urea, 2 M thiourea, 1% DTT, 0.5% amidosulfobetaine-14 (ASB-14) and 4% 3-[(3-Cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS). Inclusion of low levels of ASB-14 in solutions allowed visualization of a subset of 24 new protein spots in the Live Vaccine Strain (LVS) of Francisella tularensis and 21 spots in a virulent A-strain of the pathogen. Further investigation showed that 15 of the 24 enriched LVS spots were membrane or membrane-associated proteins suggesting that the optimized lysis and solubilization solution aids in the detection of more hydrophobic proteins. This methodology is now being applied to the analysis of Francisella obtained from in vivo sources.

Bacterial Proteins↗
PubMed1999

Comparison of the in vitro activity of and pathogen responses to sparfloxacin with those of other agents in the treatment of respiratory tract, urinary tract, and skin and skin-structure infections.

The in vitro activity of and pathogen responses to sparfloxacin were compared with those of standard therapies for the treatment of patients with community-acquired pneumonia, complicated skin or skin-structure infections, urinary tract infections, acute bacterial exacerbations of chronic bronchitis, and acute maxillary sinusitis in 7 multicenter controlled trials in North America. Sparfloxacin was administered orally as a 400-mg loading dose followed by 200 mg once daily for up to 10 days. The bacteriologic efficacy of sparfloxacin (84% to 95%) was comparable to that of comparator drugs (77% to 100%). Sparfloxacin was generally 2 to 8 times more active (minimum inhibitory concentration for 90% of strains tested [MIC90]: 0.03 to 0.5 microg/mL) than comparators against common pathogens isolated in community-acquired infections, especially Streptococcus pneumoniae, including penicillin-resistant strains; Moraxella catarrhalis; Haemophilus influenzae; Streptococcus pyogenes; and Staphylococcus aureus. Sparfloxacin was also effective against Chlamydia and Mycoplasma species. The emergence of resistance was uncommon during sparfloxacin therapy (0.3% of 1100 cases). Higher area under the plasma concentration-time curve/MIC and maximum plasma concentration/MIC ratios for sparfloxacin were associated with clinical and bacteriologic efficacy, whereas lower ratios were associated with clinical and bacteriologic failure. The clinical efficacy of sparfloxacin (80% to 95%) was comparable to that obtained with the comparator drugs (71% to 92%). In addition, sparfloxacin was well tolerated and had an overall frequency of related adverse events similar to that of the comparators. There was a higher frequency of photosensitivity reactions but a lower level of digestive adverse events with sparfloxacin compared with comparators. Sparfloxacin is a suitable therapeutic alternative for the empiric treatment of respiratory tract infections owing to its favorable pharmacokinetic profile and activity against typical and atypical respiratory tract pathogens, even in geographic areas with a high incidence of penicillin resistance.

Anti-Bacterial Agents↗