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1.
J Hosp Infect ; 149: 155-164, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38705477

ABSTRACT

OBJECTIVE: To assess the residual risk of waterborne contamination by Pseudomonas aeruginosa from a water network colonized by a single genotype [sequence type (ST) 299] despite the presence of antimicrobial filters in a medical intensive care unit (ICU). METHODS: During the first 19-month period since the ICU opened, contamination of the water network was assessed monthly by collecting water upstream of the filters. Downstream water was also sampled to assess the efficiency of the filters. P. aeruginosa isolates from patients were collected and compared with the waterborne ST299 P. aeruginosa by multiplex-rep polymerase chain reaction (PCR), pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing. Cross-transmission events by other genotypes of P. aeruginosa were also assessed. RESULTS: Overall, 1.3% of 449 samples of filtered water were positive for P. aeruginosa in inoculum, varying between 1 and 104 colony-forming units/100 mL according to the tap. All P. aeruginosa hydric isolates belonged to ST299 and displayed fewer than two single nucleotide polymorphisms (SNPs). Among 278 clinical isolates from 122 patients, 10 isolates in five patients showed identical profiles to the hydric ST299 clone on both multiplex-rep PCR and PFGE, and differed by an average of fewer than five SNPs, confirming the water network reservoir as the source of contamination by P. aeruginosa for 4.09% of patients. Cross-transmission events by other genotypes of P. aeruginosa were responsible for the contamination of 1.75% of patients. DISCUSSION/CONCLUSION: Antimicrobial filters are not sufficient to protect patients from waterborne pathogens when the water network is highly contaminated. A microbiological survey of filtered water may be needed in units hosting patients at risk of P. aeruginosa infections, even when all water points-of-use are fitted with filters.


Subject(s)
Electrophoresis, Gel, Pulsed-Field , Genotype , Intensive Care Units , Pseudomonas Infections , Pseudomonas aeruginosa , Water Microbiology , Pseudomonas aeruginosa/genetics , Pseudomonas aeruginosa/isolation & purification , Pseudomonas aeruginosa/classification , Humans , Pseudomonas Infections/microbiology , Pseudomonas Infections/transmission , Filtration/instrumentation , Whole Genome Sequencing , Molecular Typing , Cross Infection/microbiology , Cross Infection/prevention & control , Risk Assessment
2.
J Glob Antimicrob Resist ; 31: 345-352, 2022 12.
Article in English | MEDLINE | ID: mdl-36347496

ABSTRACT

OBJECTIVES: Mycobacterium abscessus is an opportunistic respiratory pathogen in patients with underlying lung disease. It is infamously known for its low treatment success rates because of its resistance to multiple classes of antibiotics. Further insight into M. abscessus resistance mechanisms is needed to improve treatment options. In this in vitro study, the role of efflux pumps in reaction to antibiotic stress is explored, as well as the ability of the putative efflux inhibitors, thioridazine and verapamil, to potentiate the activity of guideline-recommended antibiotics. METHODS: To evaluate the effects of antibiotic stress on mycobacterial efflux pumps, M. abscessus subspecies abscessus was exposed to amikacin, cefoxitin, clarithromycin, clofazimine, and tigecycline for 24 hours. Transcriptomic responses were measured by RNA sequencing to gain insight into upregulation of efflux pump encoding genes. Subsequently, in time-kill kinetics assays, the above-mentioned antibiotics were combined with thioridazine and verapamil to evaluate their potentiating capacity. RESULTS: All five antibiotics led to a fold change of ≥2 Log2 in expression of one or more genes encoding transporter systems. This effect was most pronounced for the ribosome-targeting antibiotics amikacin, clarithromycin, and tigecycline. Time-kill kinetics assays demonstrated synergy between amikacin, tigecycline, clofazimine, cefoxitin, and both thioridazine and verapamil. CONCLUSION: Antibiotic stressors induce expression of efflux pump encoding genes in M. abscessus, especially antibiotics that target the ribosome. Putative efflux inhibitors thioridazine and verapamil show synergy with various guideline-recommended antibiotics, making them interesting candidates for the improvement of M. abscessus treatment.


Subject(s)
Mycobacterium abscessus , Humans , Mycobacterium abscessus/genetics , Amikacin/pharmacology , Clarithromycin/pharmacology , Tigecycline/pharmacology , Clofazimine/pharmacology , Cefoxitin/pharmacology , Microbial Sensitivity Tests , Thioridazine/pharmacology , Anti-Bacterial Agents/pharmacology , Drug Resistance, Multiple, Bacterial/genetics , Verapamil/pharmacology
3.
Med Mal Infect ; 50(2): 213-225, 2020 Mar.
Article in English | MEDLINE | ID: mdl-30266432

ABSTRACT

Severe malaria accounts for approximately 10% of all cases of imported malaria in France; cases are mainly due to Plasmodium falciparum, while other Plasmodium species are possible but uncommon (P. vivax, P. knowlesi, P. malariae, and P. ovale). On the basis of WHO criteria for endemic areas, the French criteria defining severe imported malaria in adults have been progressively adapted to the European healthcare level. Management of severe imported malaria is a diagnostic and treatment emergency and must be initially conducted in the intensive care unit. Anti-infective treatment is now based on intravenous artesunate, which must be available in every hospital of the country likely to receive severe imported malaria patients. Intravenous quinine is thus used as a second-line treatment and is restricted to limited indications. Critical care management of organ failure is essential, particularly in patients presenting with very severe malaria. To date, no adjunctive therapy (including exchange transfusion) has demonstrated clear beneficial effects.


Subject(s)
Communicable Diseases, Imported/diagnosis , Communicable Diseases, Imported/therapy , Malaria/diagnosis , Malaria/therapy , Adult , Humans , Practice Guidelines as Topic , Severity of Illness Index
4.
J Antimicrob Chemother ; 74(10): 2930-2933, 2019 10 01.
Article in English | MEDLINE | ID: mdl-31236595

ABSTRACT

BACKGROUND: Despite intensive treatment regimens, the outcome of Mycobacterium abscessus infections is extremely poor and thus novel treatment regimens are needed. Although tigecycline seems to be one of the best options currently available, its long-term use is hampered by severe toxic side effects as well as the need for intravenous administration and the relatively high concentrations required for efficacy. OBJECTIVES: To assess the in vitro activity of omadacycline against M. abscessus and compare it with the activity of tigecycline. METHODS: The concentration- and time-dependent killing capacities of omadacycline and tigecycline against M. abscessus subspecies abscessus were determined using a time-kill kinetics assay. Time-kill curves as well as concentration-effect curves were generated. RESULTS: Time-kill curves showed strong concentration-dependent antimicrobial activity for both omadacycline and tigecycline. Omadacycline showed inhibition of mycobacterial growth at 4 mg/L and mycobacterial killing at concentrations ≥16 mg/L. Tigecycline showed mycobacterial killing at concentrations ≥4 mg/L, achieving elimination at concentrations ≥16 mg/L. The concentration-effect curves after 7 days of exposure showed stasis, 1 log mycobacterial killing and 2 log mycobacterial killing at 3.3, 4.0 and 4.8 mg/L for omadacycline and 2.2, 2.7 and 3.4 mg/L for tigecycline, respectively. CONCLUSIONS: The results of this in vitro study on omadacycline activity, together with its favourable (pharmacokinetic) properties, suggest that omadacycline is a potential new agent for the treatment of M. abscessus infections.


Subject(s)
Anti-Bacterial Agents/pharmacology , Mycobacterium Infections, Nontuberculous/drug therapy , Mycobacterium abscessus/drug effects , Tetracyclines/pharmacology , Humans , Microbial Sensitivity Tests , Microbial Viability/drug effects , Tigecycline/pharmacology
5.
J Antimicrob Chemother ; 73(2): 437-447, 2018 02 01.
Article in English | MEDLINE | ID: mdl-29136155

ABSTRACT

Background: Identification of pharmacodynamic interactions is not reasonable to carry out in a clinical setting for many reasons. The aim of this work was to develop a model-informed preclinical approach for prediction of clinical pharmacodynamic drug interactions in order to inform early anti-TB drug development. Methods: In vitro time-kill experiments were performed with Mycobacterium tuberculosis using rifampicin, isoniazid or ethambutol alone as well as in different combinations at clinically relevant concentrations. The multistate TB pharmacometric (MTP) model was used to characterize the natural growth and exposure-response relationships of each drug after mono exposure. Pharmacodynamic interactions during combination exposure were characterized by linking the MTP model to the general pharmacodynamic interaction (GPDI) model with successful separation of the potential effect on each drug's potency (EC50) by the combining drug(s). Results: All combinations showed pharmacodynamic interactions at cfu level, where all combinations, except isoniazid plus ethambutol, showed more effect (synergy) than any of the drugs alone. Using preclinical information, the MTP-GPDI modelling approach was shown to correctly predict clinically observed pharmacodynamic interactions, as deviations from expected additivity. Conclusions: With the ability to predict clinical pharmacodynamic interactions, using preclinical information, the MTP-GPDI model approach outlined in this study constitutes groundwork for model-informed input to the development of new and enhancement of existing anti-TB combination regimens.


Subject(s)
Antitubercular Agents/pharmacology , Drug Combinations , Drug Interactions , Mycobacterium tuberculosis/drug effects , Microbial Viability/drug effects , Models, Statistical
6.
Tuberculosis (Edinb) ; 105: 80-85, 2017 07.
Article in English | MEDLINE | ID: mdl-28610791

ABSTRACT

Novel treatment strategies for tuberculosis are urgently needed. Many different preclinical models assessing anti-tuberculosis drug activity are available, but it is yet unclear which combination of models is most predictive of clinical treatment efficacy. The aim of this study was to determine the role of our in vitro time kill-kinetics assay as an asset to a predictive preclinical modeling framework assessing anti-tuberculosis drug activity. The concentration- and time-dependent mycobacterial killing capacities of six anti-tuberculosis drugs were determined during exposure as single drugs or in dual, triple and quadruple combinations towards a Mycobacterium tuberculosis Beijing genotype strain and drug resistance was assessed. Streptomycin, rifampicin and isoniazid were most active against fast-growing M. tuberculosis. Isoniazid with rifampicin or high dose ethambutol were the only synergistic drug combinations. The addition of rifampicin or streptomycin to isoniazid prevented isoniazid resistance. In vitro ranking showed agreement with early bactericidal activity in tuberculosis patients for some but not all anti-tuberculosis drugs. The time-kill kinetics assay provides important information on the mycobacterial killing dynamics of anti-tuberculosis drugs during the early phase of drug exposure. As such, this assay is a valuable component of the preclinical modeling framework.


Subject(s)
Antitubercular Agents/pharmacology , Drug Discovery/methods , Mycobacterium tuberculosis/drug effects , Tuberculosis/drug therapy , Bacterial Load/drug effects , Dose-Response Relationship, Drug , Drug Resistance, Bacterial , Drug Synergism , Drug Therapy, Combination , Genotype , Humans , Kinetics , Microbial Sensitivity Tests , Microbial Viability/drug effects , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/growth & development , Tuberculosis/diagnosis , Tuberculosis/microbiology
7.
Int J Antimicrob Agents ; 49(3): 302-307, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28162983

ABSTRACT

Current treatment for tuberculosis (TB) is complicated by the emergence of multidrug resistant TB (MDR-TB). As a result, there is an urgent need for new powerful anti-TB regimens and novel strategies. In this study, we aimed to potentiate a moxifloxacin + linezolid backbone as treatment for MDR-TB with the efflux pump inhibitors verapamil and timcodar as well as with drugs that act on mycobacterial cell wall stability such as colistin and SQ109. Using a time-kill kinetics assay, the activities of moxifloxacin, linezolid, verapamil, timcodar, colistin and SQ109 as single drugs against Mycobacterium tuberculosis were evaluated. In addition, the activity of the moxifloxacin + linezolid backbone in combination with one of the potentiator drugs was assessed. As little as 0.125 mg/L moxifloxacin achieved 99% killing of M. tuberculosis after 6 days of exposure. Linezolid showed moderate killing but 99% killing was not achieved. Verapamil, timcodar and colistin only resulted in killing with the highest concentrations tested but 99% killing was not achieved. SQ109 resulted in complete elimination after 1 day of exposure to 256 mg/L and in 99% elimination after 6 days of exposure to 1 mg/L. Furthermore, colistin added to the moxifloxacin + linezolid backbone resulted in increased elimination, whereas verapamil, timcodar and SQ109 showed no added value to the backbone. This finding that colistin potentiates the activity of the moxifloxacin + linezolid backbone against M. tuberculosis suggests its potential role in further studies on the applicability of a moxifloxacin + linezolid treatment of MDR-TB.


Subject(s)
Antitubercular Agents/pharmacology , Drug Interactions , Fluoroquinolones/pharmacology , Linezolid/pharmacology , Microbial Viability/drug effects , Mycobacterium tuberculosis/drug effects , Colony Count, Microbial , Moxifloxacin , Mycobacterium tuberculosis/physiology
8.
Plast Reconstr Surg Glob Open ; 4(10): e1039, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27826466

ABSTRACT

BACKGROUND: Large defects arising from extirpation surgery of buttock sarcomas requiring adjuvant radiotherapy are best closed with flap surgery. The traditional solutions are derived from an approach to pressure sores, which were designed for the ischial, sacral, or trochanteric areas, and have now been adapted for true buttock defects. This invariably destroys the esthetics of the buttock. We describe a novel technique of sigmoidplasty, which preserves most of the esthetic features. METHODS: We report on a retrospective review of 11 consecutive buttock sarcomas managed at our institution between 2009 and 2014, focusing on those for which the described reconstruction method was used (N = 5). RESULTS: The immediate outcome was very good. In 1 patient, partial loss of 1 of the flaps and the management thereof resulted in a minor contour deformity. In general, the buttock volume was significantly decreased but the shape was preserved. This was obtained without secondary donor defect and with minimal contour irregularity. Long-term follow-up remained pleasing, and all patients were satisfied with the outcomes. CONCLUSIONS: The described technique of buttock defect closure satisfies the oncoplastic principles of tumor surgery with the added benefit of superior esthetics. We suggest that it is a versatile adjunct to the reconstructive surgeon's armamentarium for buttock reconstruction after sarcoma excision, particularly when the gluteal artery perforator systems are unavailable.

9.
PLoS One ; 10(6): e0129150, 2015.
Article in English | MEDLINE | ID: mdl-26060995

ABSTRACT

Staphylococcus aureus carriers with S. aureus bacteremia may have a reduced mortality risk compared to non-carriers. A role for the immune system is suggested. Here, we study in mice the effect of mild S. aureus skin infection prior to endogenous or exogenous S. aureus bacteremia, and evaluate protection in relation to anti-staphylococcal antibody levels. Skin infections once or twice by a clinical S. aureus isolate (isolate P) or S. aureus strain 8325-4 were induced in mice free of S. aureus and anti-staphylococcal antibodies. Five weeks later, immunoglobulin G (IgG) levels in blood against 25 S. aureus antigens were determined, and LD50 or LD100 bacteremia caused by S. aureus isolate P was induced. S. aureus skin infections led to elevated levels of anti-staphylococcal IgG in blood. One skin infection improved the course of subsequent severe endogenous bacteremia only. A second skin infection further improved animal survival rate, which was associated with increased pre-bacteremia IgG levels against Efb, IsaA, LukD, LukE, Nuc, PrsA and WTA. In conclusion, S. aureus isolate P skin infection in mice reduces the severity of subsequent endogenous S. aureus bacteremia only. Although cellular immune effects cannot be rules out, anti-staphylococcal IgG against specified antigens may contribute to this effect.


Subject(s)
Antibodies, Bacterial/blood , Bacteremia/prevention & control , Immunoglobulin G/blood , Skin Diseases, Infectious/microbiology , Staphylococcal Infections/prevention & control , Animals , Antigens, Bacterial/immunology , Bacteremia/immunology , Disease Models, Animal , Female , Mice , Skin Diseases, Infectious/immunology , Staphylococcal Infections/immunology , Staphylococcus aureus/immunology , Survival Analysis
10.
Ann Fr Anesth Reanim ; 33(4): 232-9, 2014 Apr.
Article in French | MEDLINE | ID: mdl-24684836

ABSTRACT

OBJECTIVE: Describe systemic antifungal therapy in non-neutropenic adult patients in intensive care unit (ICU). PATIENTS AND METHOD: A prospective, observational study was conducted during the first half of 2010 in the 7 ICU in a hospital with medical consultant on antimicrobial therapy. All non-neutropenic consecutive adult patients receiving systemic antifungal therapy for documented or suspected invasive fungal infection (IFI) apart from aspergillosis were included. RESULTS: Out of 1502 patients admitted in ICU, 104 (7 %) underwent systemic antifungal therapy, including 30 (29 %) for a documented IFI and 74 (71 %) for a suspected IFI. Candida albicans was identified in 23 (77 %) of the IFI and 45/52 (86 %) of the broncho-pulmonary and/or urinary colonizations in suspected IFI. Echinocandin was significantly more prescribed in patients with a documented infection (19/30 patients) and fluconazole in patients with a suspected infection (48/74 patients). The first line therapy was primarily stopped after recovery (11/30 patients) or de-escalation (9/30 patients) in documented infections, and for lack of indication (34/74 patients) or due to recovery (21/74 patients) in suspected infections after on average of 7 days of treatment. CONCLUSION: For ICU non-neutropenic adult patients in our center, antifungal therapy is prescribed two times out of three for suspected, unproved infections, in most cases with fluconazole. Documented infections were more often treated by echinocandin with secondary de-escalation. An interventional prospective study to assess the role of antifungal pre-emptive or empirical therapy is necessary.


Subject(s)
Antifungal Agents/therapeutic use , Candidiasis/drug therapy , Adult , Aged , Candida albicans , Candidiasis/microbiology , Critical Illness , Drug Utilization , Echinocandins/therapeutic use , Female , Fluconazole/therapeutic use , Humans , Male , Middle Aged , Prospective Studies , Risk Factors
11.
Vet Res ; 44: 4, 2013 Jan 22.
Article in English | MEDLINE | ID: mdl-23339425

ABSTRACT

At present, the immune response of pigs in relation to Staphylococcus aureus carriage is poorly understood. This study was aimed at investigating the dynamics of the anti-staphylococcal humoral immune response in methicillin-susceptible S. aureus (MSSA)-positive piglets and at assessing the effect of the experimental introduction of a methicillin-resistant S. aureus (MRSA) Sequence Type (ST) 398 strain. Therefore, serum samples were collected at different times from 31 weaned piglets originating from four different sows. Twenty-four out of the 31 piglets were challenged with MRSA ST398. The serum samples were analyzed for IgG antibodies to 39 S. aureus antigens, using a multiplex bead-based assay (xMAP technology, Luminex Corporation). Though antibody responses showed broad inter-individual variability, serological results appeared to be clustered by litter of origin. For most antigens, an age-related response was observed with an apparent increase in antibody titers directed against staphylococcal microbial surface components recognizing adhesive matrix molecules (MSCRAMM), which have been shown to play a role in S. aureus colonization. In most animals, antibody titers directed against staphylococcal toxins or immune-modulating proteins decreased with age, possibly reflecting the absence of bacterial invasion. The introduction of MRSA ST398 did not elicit a significant humoral immune reaction.This study describes, for the first time, the humoral immune response in weaned pigs colonized with S. aureus.


Subject(s)
Antibodies, Bacterial/blood , Methicillin-Resistant Staphylococcus aureus/pathogenicity , Staphylococcal Infections/veterinary , Staphylococcus aureus/pathogenicity , Swine Diseases/immunology , Virulence Factors/genetics , Animals , Female , Immunity, Humoral , Immunoglobulin G/blood , Male , Methicillin-Resistant Staphylococcus aureus/genetics , Methicillin-Resistant Staphylococcus aureus/metabolism , Staphylococcal Infections/blood , Staphylococcal Infections/microbiology , Staphylococcus aureus/genetics , Staphylococcus aureus/metabolism , Swine , Swine Diseases/blood , Swine Diseases/microbiology , Virulence Factors/metabolism
12.
Appl Ergon ; 44(6): 929-39, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23164199

ABSTRACT

Web-based tools developed in the last couple of years offer unique opportunities to effectively support scientists in their effort to collaborate. Communication among environmental researchers often involves not only work with geographical (spatial), but also with temporal data and information. Literature still provides limited documentation when it comes to user requirements for effective geo-collaborative work with spatio-temporal data. To start filling this gap, our study adopted a User-Centered Design approach and first explored the user requirements of environmental researchers working on distributed research projects for collaborative dissemination, exchange and work with spatio-temporal data. Our results show that system design will be mainly influenced by the nature and type of data users work with. From the end-users' perspective, optimal conversion of huge files of spatio-temporal data for further dissemination, accuracy of conversion, organization of content and security have a key role for effective geo-collaboration.


Subject(s)
Geographic Information Systems , Needs Assessment , Software Design , User-Computer Interface , Cooperative Behavior , Data Display , Ecology , Focus Groups , Geographic Mapping , Geography , Geology , Humans , Hydrology , Internet , Spatio-Temporal Analysis , Surveys and Questionnaires
14.
Clin Vaccine Immunol ; 19(6): 914-8, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22539468

ABSTRACT

A prospective clinical cohort study was established to investigate the humoral immune response in middle ear fluids (MEF) and serum against bacterial surface proteins in children suffering from recurrent acute otitis media (rAOM) and chronic otitis media with effusion (COME), using Luminex xMAP technology. The association between the humoral immune response and the presence of Moraxella catarrhalis and Streptococcus pneumoniae in the nasopharynx and middle ear was also studied. The levels of antigen-specific IgG, IgA, and IgM showed extensive interindividual variation. No significant differences in anti-M. catarrhalis and anti-S. pneumoniae serum and MEF median fluorescence intensity (MFI) values (anti-M. catarrhalis and antipneumococcal IgG levels) were observed between the rAOM or COME groups for all antigens tested. No significant differences were observed for M. catarrhalis and S. pneumoniae colonization and serum IgG levels against the Moraxella and pneumococcal antigens. Similar to the antibody response in serum, no significant differences in IgG, IgA, and IgM levels in MEF were observed for all M. catarrhalis and S. pneumoniae antigens between OM M. catarrhalis- or S. pneumoniae-positive and OM M. catarrhalis- or S. pneumonia-negative children suffering from either rAOM or COME. Finally, results indicated a strong correlation between antigen-specific serum and MEF IgG levels. We observed no significant in vivo expressed anti-M. catarrhalis or anti-S. pneumoniae humoral immune responses using a range of putative vaccine candidate proteins. Other factors, such as Eustachian tube dysfunction, viral load, and genetic and environmental factors, may play a more important role in the pathogenesis of OM and in particular in the development of rAOM or COME.


Subject(s)
Antibodies, Bacterial/blood , Antigens, Bacterial/immunology , Moraxella catarrhalis/immunology , Moraxellaceae Infections/immunology , Otitis Media with Effusion/microbiology , Pneumococcal Infections/immunology , Streptococcus pneumoniae/immunology , Antigens, Surface/immunology , Child, Preschool , Chronic Disease , Cohort Studies , Female , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Infant , Infant, Newborn , Male , Moraxellaceae Infections/microbiology , Nasopharynx/microbiology , Otitis Media with Effusion/immunology , Pneumococcal Infections/microbiology , Prospective Studies , Recurrence
15.
Infect Immun ; 80(6): 2186-93, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22451514

ABSTRACT

Knowledge of the immunological correlates of Staphylococcus aureus and Streptococcus pneumoniae colonization is required for the search for future protein vaccines. We evaluated natural antibody levels against pneumococcal and staphylococcal proteins in relation to previous bacterial colonization with both pathogens. In a randomized controlled trial, nasopharyngeal samples were obtained from children at 1.5, 6, 12, 18, and 24 months and cultured for S. aureus and S. pneumoniae. Approximately 50% of the children were PCV7 vaccinated. Serum IgG against 18 pneumococcal and 40 staphylococcal proteins was semiquantified by Luminex technology from 111 12 month olds and 158 24 month olds. Previous culture-proven S. aureus colonization was associated with higher IgG levels against 6/40 staphylococcal proteins (ClfB, ClfA, Efb, CHIPS, LukD, and LukF [P ≤ 0.001]) compared to noncarriers. Previous pneumococcal colonization was associated with increased IgG levels against 12/18 pneumococcal proteins compared to noncarriers (P ≤ 0.003). Increasing age was associated with higher levels of antibodies to most pneumococcal proteins and lower levels of antibodies to over half the staphylococcal proteins, reflecting natural colonization dynamics. Anti-S. pneumoniae and anti-S. aureus protein antibodies at the age of 12 months were not negatively correlated with subsequent colonization with the homologous species in the following year and did not differ between PCV7-vaccinated and nonvaccinated children. Colonization with S. aureus and S. pneumoniae induces serum IgG against many proteins, predominantly proteins with immune-modulating functions, irrespective of PCV7 vaccination. None of them appeared to be protective against new acquisition with both pathogens, possibly due to the polymorphic nature of those proteins in the circulating bacterial population.


Subject(s)
Antibodies, Bacterial/blood , Nasopharynx/microbiology , Pneumococcal Infections/immunology , Staphylococcal Infections/immunology , Staphylococcus aureus/immunology , Streptococcus pneumoniae/immunology , Aging , Antibodies, Bacterial/immunology , Antibody Specificity , Bacterial Proteins/immunology , Carrier State/immunology , Child, Preschool , Humans , Immunoglobulin G/blood , Infant , Staphylococcus aureus/isolation & purification , Streptococcus pneumoniae/isolation & purification , Virulence Factors/immunology
16.
PLoS One ; 6(10): e26170, 2011.
Article in English | MEDLINE | ID: mdl-22028827

ABSTRACT

Currently, there is no animal model known that mimics natural nasal colonization by Staphylococcus aureus in humans. We investigated whether rhesus macaques are natural nasal carriers of S. aureus. Nasal swabs were taken from 731 macaques. S. aureus isolates were typed by pulsed-field gel electrophoresis (PFGE), spa repeat sequencing and multi-locus sequence typing (MLST), and compared with human strains. Furthermore, the isolates were characterized by several PCRs. Thirty-nine percent of 731 macaques were positive for S. aureus. In general, the macaque S. aureus isolates differed from human strains as they formed separate PFGE clusters, 50% of the isolates were untypeable by agr genotyping, 17 new spa types were identified, which all belonged to new sequence types (STs). Furthermore, 66% of macaque isolates were negative for all superantigen genes. To determine S. aureus nasal colonization, three nasal swabs from 48 duo-housed macaques were taken during a 5 month period. In addition, sera were analyzed for immunoglobulin G and A levels directed against 40 staphylococcal proteins using a bead-based flow cytometry technique. Nineteen percent of the animals were negative for S. aureus, and 17% were three times positive. S. aureus strains were easily exchanged between macaques. The antibody response was less pronounced in macaques compared to humans, and nasal carrier status was not associated with differences in serum anti-staphylococcal antibody levels. In conclusion, rhesus macaques are natural hosts of S. aureus, carrying host-specific lineages. Our data indicate that rhesus macaques are useful as an autologous model for studying S. aureus nasal colonization and infection prevention.


Subject(s)
Macaca mulatta/microbiology , Phylogeny , Staphylococcus aureus/genetics , Staphylococcus aureus/isolation & purification , Animals , Evolution, Molecular , Genes, Bacterial/genetics , Humans , Immunoglobulin A/blood , Immunoglobulin A/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Macaca mulatta/blood , Nose/microbiology , Species Specificity , Staphylococcus aureus/immunology
17.
Vaccine ; 29(34): 5603-10, 2011 Aug 05.
Article in English | MEDLINE | ID: mdl-21704103

ABSTRACT

The primary Moraxella catarrhalis-specific humoral immune response, and its association with nasopharyngeal colonization, was studied in a cohort of infants from birth to 2 years of age. Results indicated that the levels of antigen-specific IgG, IgA and IgM showed extensive inter-individual variability over time, with IgM and IgA levels to all 9 recombinant domains, from 7 different OMPs, being relatively low throughout the study period. In contrast, the level of antigen-specific IgG was significantly higher for the recombinant domains Hag³58⁻85³, MID764⁻9¹³, MID96²â»¹²°°, UspA1557⁻7°4 and UspA2¹65⁻³¹8 in cord blood compared to 6 months of age (P ≤ 0.001). This was a most likely a consequence of maternal transmission of antigen-specific IgG to newborn babies, possibly indicating a future role for these 3 surface antigens in the development of an effective humoral immune response to M. catarrhalis. Finally, at 2 years of age, the levels of antigen-specific IgG still remained far below that obtained from cord blood samples, indicating that the immune response to M. catarrhalis has not matured at 2 years of age. We provide evidence that a humoral antibody response to OMPs UspA1, UspA2 and Hag/MID may play a role in the immune response to community acquired M. catarrhalis colonization events.


Subject(s)
Bacterial Outer Membrane Proteins/immunology , Bacterial Proteins/immunology , Moraxella catarrhalis/immunology , Antibodies, Bacterial/blood , Antibodies, Bacterial/immunology , Antigens, Bacterial/blood , Antigens, Bacterial/immunology , Antigens, Surface/immunology , Female , Fetal Blood/immunology , Genotype , HIV Infections/prevention & control , Humans , Immunity, Humoral , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Infant , Infant, Newborn , Maternal-Fetal Exchange/immunology , Moraxella catarrhalis/genetics , Nasopharynx/immunology , Nasopharynx/microbiology , Pregnancy
18.
Infect Immun ; 79(4): 1680-7, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21282409

ABSTRACT

The currently available pneumococcal vaccines do not protect against all serotypes of Streptococcus pneumoniae. A shift toward nonvaccine serotypes causing colonization and invasive disease has occurred, and studies on protein-based vaccines have been undertaken. We assessed the association between specific antibodies against pneumococcal virulence proteins and colonization and respiratory tract infections (RTIs). Additionally, we assessed the extent to which colonization induces a humoral immune response. Nasopharyngeal swabs collected from children at 1.5, 6, 14, and 24 months of age were cultured for pneumococcus. Serum samples were obtained at birth and at 6, 14, and 24 months (n = 57 children providing 177 serum samples). Data were collected prior to the pneumococcal vaccine era. IgG, IgA, and IgM levels against 17 pneumococcal protein vaccine candidates were measured using a bead-based flow cytometry technique (xMAP; Luminex Corporation). Information regarding RTIs was questionnaire derived. Levels of IgG against all proteins were high in cord blood, decreased in the first 6 months and increased again thereafter, in contrast to the course of IgA and IgM levels. Specific antibodies were induced upon colonization. Increased levels of IgG against BVH-3, NanA, and SP1003 at 6 months, NanA, PpmA, PsaA, SlrA, SP0189, and SP1003 at 14 months, and SlrA at 24 months were associated with a decreased number of RTIs in the third year of life but not with colonization. Maternal antipneumococcal antibodies did not protect against pneumococcal colonization and infection. Certain antibodies against pneumococcal virulence proteins, some of which are induced by colonization, are associated with a decreased number of RTIs in children. This should be taken into account in future pneumococcal vaccine studies.


Subject(s)
Antibodies, Bacterial/immunology , Pneumococcal Infections/immunology , Virulence Factors/immunology , Antibodies, Bacterial/blood , Antigens, Bacterial/immunology , Cell Separation , Child, Preschool , Female , Fetal Blood/immunology , Flow Cytometry , Humans , Infant , Male , Pneumococcal Infections/epidemiology , Pneumococcal Vaccines/immunology , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/immunology , Respiratory Tract Infections/microbiology , Streptococcus pneumoniae/immunology
19.
J Immunol Methods ; 365(1-2): 142-8, 2011 Feb 28.
Article in English | MEDLINE | ID: mdl-21185300

ABSTRACT

Staphylococcus aureus causes a variety of infections. Knowledge about the physiological role of most S. aureus antigens in colonization and infection is only limited. This can be studied by measuring antigen-specific antibody responses. In this study, we optimized the multiplex microsphere bead-based flow cytometry technique for mouse serum samples. We analysed immunoglobulin G (IgG) levels directed against 26 S. aureus proteins in a single small-volume mouse serum sample. We assessed possible cross reactivity. Furthermore, we analysed serum samples from mice with different types of S. aureus infections caused by different S. aureus strains. The results show that cross reactivity between proteins on microspheres and serum antibodies towards other proteins was limited. We found that lung-infected mice had a higher and broader IgG response than skin-infected mice. Clearly, the site of infection influences the IgG profile. Next, we compared sera from mice with intravenously-induced bacteraemia caused by different S. aureus strains. We showed different IgG responses depending on the causing S. aureus strain. It is concluded that the bead-based multiplex S. aureus antibody assay can be successfully applied to determine the immunogenicity of different S. aureus proteins in relation to the site of infection and the S. aureus strain causing the infection.


Subject(s)
Antibodies, Bacterial/analysis , Immunoassay/methods , Staphylococcal Infections/immunology , Staphylococcal Infections/microbiology , Staphylococcus aureus , Animals , Antibodies, Bacterial/blood , Antigens, Bacterial/immunology , Bacteremia/immunology , Bacteremia/microbiology , Bacterial Proteins/immunology , Cross Reactions , Female , Flow Cytometry/methods , Immunoglobulin G/analysis , Immunoglobulin G/blood , Mice , Mice, Inbred BALB C , Microspheres , Pneumonia, Staphylococcal/immunology , Pneumonia, Staphylococcal/microbiology , Reproducibility of Results , Staphylococcal Skin Infections/immunology , Staphylococcal Skin Infections/microbiology , Staphylococcal Vaccines/administration & dosage , Staphylococcus aureus/classification , Staphylococcus aureus/immunology
20.
Ann Fr Anesth Reanim ; 30(1): 80-2, 2011 Jan.
Article in French | MEDLINE | ID: mdl-21159484

ABSTRACT

We report a case of a Pseudomonas aeruginosa septicemia complicated by a septic shock after chemotherapy for pulmonary cancer. Bilateral legs necrotic purpura corresponding to echtyma gangrenosum lesions (erythematous inflammatory halo, positive bacteriologic cutaneous biopsy) was noted 48 h previous to the shock. Echtyma gangrenosum manifestation should alert physician to P. aeruginosa septicemia risk and can be useful to guide probabilist antibiotherapy.


Subject(s)
Gangrene/complications , Pseudomonas Infections/complications , Sepsis/complications , Adenocarcinoma/complications , Adenocarcinoma/drug therapy , Antineoplastic Agents/adverse effects , Brain Neoplasms/secondary , Critical Care , Gangrene/microbiology , Humans , Intensive Care Units , Lung Neoplasms/complications , Lung Neoplasms/drug therapy , Male , Middle Aged , Necrosis , Neutropenia/chemically induced , Neutropenia/complications , Pseudomonas Infections/microbiology , Sepsis/microbiology , Shock, Septic/complications , Shock, Septic/microbiology , Skin/microbiology
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