High rates of quinolone-resistant strains of Shigella sonnei in HIV-infected MSM.

PURPOSE: There is increasing evidence that shigellosis is a predominantly sexually transmitted disease among men who have sex with men (MSM) and that infection with the human immunodeficiency virus (HIV) is a risk factor for shigellosis. METHODS: Retrospective analysis of antibiotic resistance profiles of Shigella species isolated from stool specimens of patients presenting with diarrhea from January 2010 to July 2012 in three German outpatient clinics specialized in HIV care. RESULTS: Among 79 cases of Shigella sonnei, 56 occurred in HIV-infected MSM, while 23 were observed in HIV-negative MSM. High resistance rates (>90%) were found for doxycycline, tetracycline, aminoglycosides, all cephalosporins of first and second generations tested, and trimethoprim/sulfamethoxazole. In total, 54% of cases were resistant to ciprofloxacin. Compared to negative subjects, HIV-infected MSM had a significantly higher rate of quinolone resistance. For ciprofloxacin, the resistance rates were 66 versus 24%, respectively (p = 0.0016). Individual resistance patterns did not indicate that this was due to a limited outbreak. Rates of resistance to other antibiotics than quinolones showed no differences between HIV-infected and HIV-negative cases. No resistance was found for carbapenems or newer cephalosporins such as ceftriaxone. CONCLUSIONS: The high rates of S. sonnei isolates resistant to quinolones and other traditional antibiotics are of concern. Innovative prevention efforts are urgently needed. The empirical use of quinolones in HIV-infected patients presenting with S. sonnei infection is no longer recommended.

[Diagnosis of infections in pneumology]. / Infektionsdiagnostik in der Pneumologie.

Lower respiratory tract infections rank among the leading causes of morbidity and mortality worldwide. In clinical practice, especially in the care of severely ill patients, discrimination between tracheobronchial colonisation with potentially pathogenic microorganisms and infection is a common diagnostic challenge. While prompt antibiotic treatment is needed in critically ill patients with pneumonia, an inadequate use of antibiotics is the major cause for the emergence of drug-resistant microorganisms. The first part of this review provided a detailed overview of the currently available methods for the diagnosis of pulmonary infectious diseases. In the present second part of the manuscript, we focus upon methods and criteria for the differentiation between lower respiratory tract bacterial colonisation and lower respiratory tract infections, highlighting important pathogens.

[Diagnosis of infections in pneumology]. / Infektionsdiagnostik in der Pneumologie.

Lower respiratory tract infections play an important role in the ambulatory and hospital health-care sectors. State-of-the-art diagnoses of lower respiratory tract infections and methods to differentiate bacterial lower respiratory tract infections from colonisation have been described in the first two parts of this review series. The present article summarises current diagnostic methods and treatment indications for viral and fungal respiratory infections. These recommendations may guide clinicians in their decision to prescribe or withhold antibiotic therapies in daily clinical practice.

A phase 1 study of the safety, reactogenicity, and immunogenicity of a Schistosoma mansoni vaccine with or without glucopyranosyl lipid A aqueous formulation (GLA-AF) in healthy adults from a non-endemic area.

BACKGROUND: Schistosomiasis caused by Schistosoma mansoni (Sm) is a chronic, debilitating and potentially deadly neglected tropical disease. The licensure of a vaccine to prevent schistosomiasis would represent a major breakthrough in public health. METHODS: The safety and immunogenicity of a candidate Sm vaccine were assessed in this phase I, double-blind, dose-escalation trial. Seventy-two healthy Sm-naïve 18-50 year olds were randomized to receive 3 doses ∼ 8 weeks apart of saline placebo, or 10 µg, 30 µg, or 100 µg of recombinant Sm-Tetraspanin-2 vaccine formulated on aluminum hydroxide adjuvant (Sm-TSP-2/Al) with or without 5 µg of glucopyranosyl lipid A aqueous formulation (GLA-AF). Clinical and serologic responses were assessed for 1 year after dose 3. RESULTS: Vaccines were safe and well-tolerated. The most common reactions were injection site tenderness and pain, and headache and fatigue. Tenderness and pain were more frequent in groups receiving vaccine with GLA-AF than placebo (p = 0.0036 and p = 0.0014, respectively). Injection site reactions among those given Sm-TSP-2/Al with GLA-AF lasted 1.22 and 1.33 days longer than those receiving Sm-TSP-2/Al without GLA-AF or placebo (p < 0.001 for both). Dose- and adjuvant-related increases in serum IgG against Sm-TSP-2 were observed. Peak IgG levels occurred 14 days after dose 3. Seroresponse frequencies were low among recipients of Sm-TSP-2/Al without GLA-AF, but higher among subjects receiving 30 µg or 100 µg of Sm-TSP-2/Al with GLA-AF. More seroresponses were observed among those given 30 µg or 100 µg of Sm-TSP-2/Al with GLA-AF compared to placebo (p = 0.023 and p < 0.001, respectively). Seroresponse frequencies were 0%, 30%, 50%, and 89%, respectively, among those given placebo, or 10 µg, 30 µg or 100 µg of Sm-TSP-2/Al with GLA-AF, suggesting a dose-response relationship for Sm-TSP-2/Al with GLA-AF (p = 0.0001). CONCLUSIONS: Sm-TSP-2/Al with or without GLA-AF was safe and well tolerated in a Sm-naïve population. A vaccine like the one under development may represent our best hope to eliminating this neglected tropical disease.

Extended-spectrum beta-lactamase production is associated with an increase in cell invasion and expression of fimbrial adhesins in Klebsiella pneumoniae.

Extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae strains are suggested to possess higher pathogenic potential than non-ESBL producers. Microbial adherence to and invasion of host cells are critical steps in the infection process, so we examined the expression of type 1 and 3 fimbrial adhesins by 58 ESBL-producing and 152 nonproducing isolates of K. pneumoniae and their abilities to invade ileocecal and bladder epithelial cells. Mannose-sensitive hemagglutination of guinea pig erythrocytes and mannose-resistant hemagglutination of ox erythrocytes were evaluated to determine the strains' abilities to express type 1 and type 3 fimbriae, respectively. Bacterial adhesion to and invasion of epithelial cells were tested by enzyme-linked immunosorbent assay and imipenem killing assay, respectively. The adherence of ESBL- and non-ESBL-producing strains to epithelial cells did not differ significantly (P > 0.05). In contrast, the proportion of strains capable of invading (>5% relative invasion) ileocecal and bladder epithelial cells was significantly higher among ESBL producers (81%, n = 47/58, and 27.6%, n = 16/58, respectively) than among non-ESBL producers (61%, n = 93/152, and 10%, n = 15/152, respectively) (P = 0.0084, odds ratio [OR] = 2.711, 95% confidence interval [CI] = 1.302 to 5.643 and P = 0.0021, OR = 4.79, 95% CI = 1.587 to 7.627). The mean invasion by ESBL producers (5.5% +/- 2.8% and 3.3% +/- 2.7%, respectively) was significantly higher than that by non-ESBL producers (2.9% +/- 2.6% and 1.8% +/- 2%, respectively) (P < 0.0001). Likewise, the proportion of ESBL producers coexpressing both fimbrial adhesins was significantly higher (79.3%; n = 46/58) than that of non-ESBL producers (61.8%; n = 94/152) (P = 0.0214; OR = 2,365; 95% CI = 1.157 to 4.834). Upon acquisition of SHV-12-encoding plasmids, two transconjugants switched on to produce type 3 fimbriae while expression of type 1 fimbriae was not affected. The acquisition of an ESBL plasmid appeared to upregulate the phenotypic expression of one or more genes, resulting in greater invasion ability.

[What should be considered in acute diarrhea?]. / Was ist bei akuter Diarrhö zu beachten?

This article provides an overview of possible causes, differential diagnosis, diagnostics and therapy of acute diarrhea.

Humoral immune response to Klebsiella capsular polysaccharides in HLA-B27-positive patients with acute anterior uveitis and ankylosing spondylitis.

Klebsiella is suggested to trigger ankylosing spondylitis (AS) and acute anterior uveitis (AAU) in HLA-B27-positive individuals. Previous investigations showed an increased antibody response to the Klebsiella capsular types K26, K36, and K50 in sera from HLA-B27-positive AS patients. In the present study the prevalence and titers of antibodies against Klebsiella capsular antigens were measured by means of an ELISA in 32 sera from HLA-B27-positive AAU patients either with (n = 10) or without AS (n = 22) and compared with sera from HLA-B27-negative AS-patients (n = 13). Sera from either HLA-B27-positive (n = 45) or negative (n = 40) healthy individuals served as control. Sera from HLA-B27-positive AAU with or without AS showed significantly higher antibody prevalence and IgG-titers against capsular antigens of the Klebsiella serotypes K26, K36, and K50 when compared with sera from HLA-B27-negative AS patients or with healthy controls. These results might be taken to indicate the predominance of these serotypes in the HLA-B27-associated AS and AAU.

Inability of encapsulated Klebsiella pneumoniae to assemble functional type 1 fimbriae on their surface.

We screened phase variants of Klebsiella pneumoniae isolates for the expression of capsule and type 1 fimbriae and found that all of the 22 blood isolates were encapsulated and did not express type 1 fimbriae while 10 of 11 urinary tract isolates expressed type 1 fimbriae but were unencapsulated. Phase variants from selected isolates were found to be either unencapsulated and fimbriated or lacked both structures. Variants expressing both structures were not detected. Fimbrial subunits FimH and FimA were localized in the periplasmic space of the parent strain and on the surface of the unencapsulated variants. The results suggest that capsule formation impedes assembly of pre-formed fimbrial subunits on the bacterial surface.

Recurrent tuberculosis in Houston, Texas: a population-based study.

OBJECTIVE: To determine the predictors of recurrence of tuberculosis (TB), the drug resistance pattern of Mycobacterium tuberculosis strains recovered from recurrent TB patients, and the frequency of re-infection with a new M. tuberculosis strain among patients with recurrent disease. DESIGN: A population-based, retrospective case-control study using the Houston Tuberculosis Initiative database. RESULTS: We found that, among 100 patients with recurrent TB who completed adequate therapy for a first episode of TB, not receiving directly observed therapy, pulmonary disease, HIV/AIDS diagnosis, not having a family physician, being unemployed and using public transportation were predictors of recurrent disease. There was a significant increase in drug-resistant M. tuberculosis strains in the second episode of disease compared to the first episode (21.3% vs. 8.2%, P = 0.04). Exogenous re-infection with a new strain of M. tuberculosis was found to cause 24-31% of recurrent TB. CONCLUSION: Recurrent TB in Houston is associated with a significant increase in drug-resistant M. tuberculosis strains. Re-infection with a new M. tuberculosis strain causes a significant proportion of recurrent TB in an area of low TB incidence. Patients with HIV/AIDS constitute a population at increased risk of disease recurrence.

5' dinucleotide repeat polymorphism of NRAMP1 and susceptibility to tuberculosis among Caucasian patients in Houston, Texas.

SETTING: Houston Tuberculosis Initiative (HTI) and Baylor College of Medicine, Houston, Texas. OBJECTIVE: To further explore the association between the polymorphisms of NRAMP1 and human susceptibility/resistance to tuberculosis (TB), specifically to determine whether the reported association shown for blacks and Asians holds true for Caucasian populations. DESIGN: In a case-control study, 135 adult Caucasian TB patients and 108 adult Caucasian HIV-seronegative non-TB controls were analyzed for the association between the polymorphisms in NRAMP1 gene and clinical TB. RESULTS: Heterozygote at 5'(GT)n, a dinucleotide repeat polymorphism in the promoter of NRAMP1, was observed at significantly higher frequencies among HIV-negative patients with pulmonary TB (41.6%; OR 2.02; 95%CI 1.11-3.64), extra-pulmonary TB (66.7%; OR 4.80; 95%CI 1.34-17.15), and HIV-seropositive TB patients (50%; OR 3.77; 95%CI 1.33-10.66) in comparison with the controls (27.8%). Homozygotes (GT)(10,10) were over-represented among HIV-positive TB patients (18.2%; OR 6.86; 95%CI 1.55-30.21) compared to the controls (5.5%). CONCLUSION: These findings suggest that the 5'(GT)n polymorphism of NRAMP1 modifies TB susceptibility in this Caucasian population, and could possibly be related to the site of infection among HIV-negative individuals and HIV-coinfected TB.

Isolation of Enterobacteriaceae from the mouth and potential association with malodor.

Bad breath is a common phenomenon, usually the result of bacterial metabolism in the oral cavity. It is generally accepted that Gram-negative bacteria are responsible for this problem, largely through degradation of proteinaceous substances. In initial experiments, screening of malodorous isolates following outgrowth of samples obtained from saliva, periodontal pockets, and the tongue dorsum yielded enterobacterial isolates. Clinical studies were conducted to examine the prevalence of such bacteria in four different populations: orthodontic patients, malodor clinic patients, complete-denture wearers, and a healthy young population. The prevalence of Enterobacteriaceae in the oral cavities of the denture-wearing population was very high (48.0%) as compared with the other groups: 27.1% in the malodor clinic patients, 16.4% in the normal population, and 13% among orthodontic patients. Isolates of Klebsiella and Enterobacter emitted foul odors in vitro which resembled bad breath, with concomitant production of volatile sulfides and cadaverine, both compounds related to bad breath. When incubated on a sterile denture, enterobacterial isolates produced typical denture foul odor. Isolates exhibited cell-surface hydrophobic properties when tested for adhesion to acryl and aggregation with ammonium sulphate. The results, taken together, suggest that Klebsiella and related Enterobacteriaceae may play a role in denture malodor.

Prospective randomized investigation for evaluation of postoperative changes in the microbial climate of paranasal mucosa by the use of different dissoluting techniques during postoperative care.

Endonasal dissolution by the use of NaCl-solution is a common postoperative treatment of the nasal mucosa after endonasal surgery. These procedure involve for example endonasal shower and sterilized solutions. The contamination of nasal shower in case of unprofessional cleaning after treatment was an argument against this technique in earlier discussions. The danger of such an infection should be avoided by the use of sterilized solution. Therefore the dependence of nasal microbial climate on different nasal dissoluting techniques was investigated by the use of such named endonasal shower (Siemens und Co, Bad Ems, Germany) in comparison with sterilized solution (Rhinomer, Zyma SA, Nyon, France). Microbial cultures were investigated of 80 patients after endonasal surgery (53 m, 27 f; 31 +/- 21 age). Surgery was done for the treatment of chronic polypous sinusitis. Pre-, intra- and postoperative samples were taken in 640 cases to proceed microbial cultures. Material was transferred with the use of a Port-A-Cul-transport medium and preparation of the microbial cultures was done during the first four hours. As a result 895 bacterial clones were cultivated. These consisted of 87% aerob and 13% anaerob bacteria. Staphylococcus aureus (39%) and members of the family of Enterobactericae (30%) were the most common microbes. There was neither an evidence for postoperative microbes on the nasal mucosa nor a correlation between the dissoluting technique and the postoperative outcome. The use of sterilized solutions for the postoperative care of endonasal mucosa does not cause an additional worthful effect on neither the postoperative microbial climate nor the outcome in comparison to endonasal shower.

Mycobacterium tuberculosis bacteraemia: experience from a non-endemic urban centre.

The isolation of Mycobacterium tuberculosis from blood culture specimens has been associated with human immunodeficiency virus (HIV) co-infection with variable impact on tuberculosis (TB) mortality reported. The overwhelming majority of M. tuberculosis bacteraemia cases were described in developing countries. We present a nested case-control analysis of clinical, sociodemographic and behavioural risk factors in patients with positive M. tuberculosis blood cultures compared with patients with negative blood cultures from a 9-year population-based active TB surveillance study conducted in Houston, Texas. There were 42 patients with M. tuberculosis bacteraemia, 47 blood culture negative patients and 3573 patients for whom no mycobacterial blood culture was requested. HIV infection was more common in patients for whom a mycobacterial blood culture was requested (79.8% versus 15.1% p <0.001). Of the patients with M. tuberculosis bacteraemia, six were HIV negative or had no documentation of HIV status, including five with immunosuppressive conditions other than HIV. Patients with M. tuberculosis bacteraemia were more likely than patients with negative blood cultures to be deceased at diagnosis or to die while on TB therapy (50.0% versus 17.0%, p <0.01), to report men-who-have-sex-with-men behaviour (31.7% versus 13.0%, p 0.03), to have renal failure (28.6% versus 6.4%, p 0.01), and to have HIV RNA levels higher than 500 000 copies/mL (61.9% versus 17.2%, p ≤0.01). Requests for mycobacterial culture of blood specimens were more common in HIV-infected individuals, and the presence of M. tuberculosis bacteraemia was associated with a significant increase in mortality.

Safety and immunogenicity of a recombinant nonglycosylated erythrocyte binding antigen 175 Region II malaria vaccine in healthy adults living in an area where malaria is not endemic.

Erythrocyte binding antigen region II (EBA-175) is a conserved antigen of Plasmodium falciparum that is involved in binding of the parasite to the host's erythrocytes. We evaluated the safety and immunogenicity of a recombinant EBA-175 vaccine with aluminum phosphate adjuvant in healthy young adults living in the United States. Eighteen subjects/group received ascending doses (5, 20, 80, or 160 µg) of the vaccine at 0, 1, and 6 months; 8 subjects received placebo. Most of the injection site and systemic reactions were mild to moderate in intensity. After 2 or 3 doses of the vaccine at any concentration, antibody levels measured by enzyme-linked immunosorbent assay were significantly higher than those for the placebo group. Sera from subjects who received 3 doses of the vaccine at any concentration inhibited the growth of erythrocyte-stage P. falciparum at low levels compared to sera from placebo recipients or preimmune sera. In conclusion, the EBA-175 vaccine with adjuvant was safe and immunogenic in malaria-naïve subjects.

Comparative immunogenicity of recombinant influenza hemagglutinin (rHA) and trivalent inactivated vaccine (TIV) among persons > or =65 years old.

Alternative substrates for influenza vaccine production are needed to ensure adequate supplies. We evaluated the relative safety and immunogenicity of recombinant hemagglutinin (rHA) or trivalent inactivated vaccine (TIV) among 869 > or =65-year-old subjects in a randomized clinical trial. Virologic surveillance for influenza-like illness (ILI) was conducted during the 2006-2007 epidemic. Vaccines were well tolerated. Seroconversion rates vs. influenza A/H1N1 and H3N2 antigens were superior in the rHA group, but were inferior vs. influenza B; however, results for influenza B are confounded since the vaccine antigens were different. ILI frequencies were low and similar in both groups. Studies assessing relative immunogenicity of vaccines using identical B Ags are warranted.

Safety, reactogenicity and immunogenicity of Francisella tularensis live vaccine strain in humans.

We evaluated the safety, reactogenicity and immunogenicity of escalating doses of a new Francisella tularensis Live Vaccine Strain (LVS) lot by scarification (SCAR) or subcutaneously (SQ) in humans. Subjects (N=10/group) received one dose of LVS via SCAR at 10(5),10(7) or 10(9)cfu/ml or SQ at 10(2), 10(3),10(4) or 10(5)cfu/ml; 14 subjects received placebo. All doses/routes were well tolerated. When compared to placebo, vaccination with 10(7) SCAR and 10(9) SCAR resulted in significantly higher serologic response frequencies, as measured by ELISA for IgG, IgM, IgA and microagglutination; whereas vaccination with 10(5) SCAR, 10(7) SCAR 10(9) SCAR and 10(5) SQ elicited a significantly higher interferon-gamma response frequency.

Pseudomonas aeruginosa strains from nosocomial pneumonia are more serum resistant than P. aeruginosa strains from noninfectious respiratory colonization processes.

BACKGROUND: Serum resistance is regarded as a major virulence factor of bacteria and is thought to be mediated by O side chains of the lipopolysaccharides (LPS). We investigated the serum-resistance properties and O serogroups of Pseudomonas aeruginosa strains isolated from intensive careunit (ICU) patients with pneumonia and from the respiratory tract of ICU patients without respiratory tract infections. MATERIALS AND METHODS: 171 P. aeruginosa strains were consecutively isolated from bronchoalveolar lavage fluid or transtracheal aspirates of ICU patients with monobacterial nosocomial pneumonia and 49 strains were isolated from the respiratory tract of ICU patients without respiratory tract infections. All strains were O serogrouped using Oantigen- specific sera for 14 O serogroups and tested for their sensitivity to the serum's bactericidal effect. RESULTS: Using two different analyses, the frequency of serum-sensitive isolates was significantly lower in strains from patients with pneumonia (56.1%; n = 96/171 and 22.8%, n = 39/171, respectively) than in strains from asymptomatically colonized patients (73.46%; 36/49 and 38.8%, n = 19/49, respectively) (p = 0.03; OR = 2.163; 95% CI = 1.072-4.368 and p = 0.0289; OR = 2.144; 95% CI = 1.089-4.368, respectively). O serogrouping revealed higher frequency of the serogroups A (11.9% and 16.3%, respectively), B (14.3% and 21%), E (26.5% and 24.6%), and I (28.6% and 28%) in both strain collections. The frequency of serum-sensitive strains (13/28 and 3/45, respectively) was significantly lower among strains expressing the A and B serogroups, than for all other serogroups (p < 0.05). CONCLUSION: Strains isolated from patients with pneumonia and strains possessing O-A or O-B serogroups appear to have greater pathogenic potential by virtue of their ability to resist serum-mediated killing. The linkage, however, between the O serogroups, serum resistance, and a strain's virulence remains unclear at this stage.

Hemagglutinins of Klebsiella pneumoniae and K. oxytoca isolated from different sources.

482 Klebsiella pneumoniae and K. oxytoca strains isolated from different sources (human clinical material, feces of healthy subjects, sewage) were investigated for expression of MS-(mannose-sensitive) and MR/K-(mannose-resistant, Klebsiella-like) hemagglutinins. Regardless of the source of isolation, the majority of K. pneumoniae strains induced mannose-sensitive hemagglutination, but very few K. oxytoca isolates produced this type of hemagglutinin. In both species, most strains induced MR/K-hemagglutination. In general, environmental isolates showed a lesser incidence in production of each hemagglutinin and a higher percentage of non-hemagglutinating strains than fecal and clinical strains. These results suggest clinical isolates to be phenotypically more related to fecal than to environmental strains.

[Indication for and effectiveness of fluconazole in oral candidiasis]. / Indikation und Wirksamkeit von Fluconazol bei der oralen Candidose.

From 1991 until 1993 we used fluconazole in 56 cases of oral candidosis which could not be managed by local therapy only. In seven cases there was no clinical improvement. A mycological cure was seen in 44 cases. In cases of oral candidosis which do not respond to local therapy fluconazole has proven a success especially in the follow up of patients with oral cancer and in cases of oral precancerous lesions with mycotic colonization.