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1.
Clin Oral Investig ; 28(2): 144, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38351376

RESUMO

OBJECTIVES: Recent research has demonstrated that platelet-rich fibrin (PRF) is an appropriate carrier for ampicillin/sulbactam. The aim of the study was to investigate whether PRF is also a suitable bio-carrier for clindamycin (CLI). METHODS: PRF membranes were produced from 36 patients receiving intravenous therapy with CLI (e.g. due to the diagnosis of an osteonecrosis of the jaw or infections). Concentrations of CLI in PRF membranes were measured with liquid chromatography-tandem mass spectrometry, and the antimicrobial effects were investigated in vitro in agar diffusion tests with fresh PRF and PRF stored for 24 h. Storage was performed in an incubator at 36 °C to simulate the in-vivo situation. RESULTS: The mean concentration of CLI in plasma was 1.0 ± 0.3 µg/100 mg plasma; in resulting PRF membranes 0.7 ± 0.4 µg/100 mg PRF. Agar diffusion tests were performed with Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus mitis, Porphyromonas gingivalis, and Fusobacterium nucleatum. Mean inhibition zones, in mm, for fresh PRF were 17.3, 12.2, 18.8, 17.1, 25.8 and 18.1, 12.7, 19.2, 17.3, and 26.3 for stored PRF, respectively. CONCLUSION: The results demonstrate that PRF is a suitable bio-carrier for CLI when administered systemically to patients. The concentration in PRF generated from patients after infusion of 600 mg CLI dose suffices to target clinically relevant bacteria. CLINICAL RELEVANCE: Using PRF as a carrier for local antibiotic application can prevent infections in oral and maxillofacial surgery. Within the study limitations, the findings could expand the scope of PRF application by adding CLI as a new antibiotic to the spectrum of PRF therapy.


Assuntos
Fibrina Rica em Plaquetas , Humanos , Clindamicina/farmacologia , Ágar , Antibacterianos/farmacologia , Staphylococcus aureus
2.
J Med Virol ; 95(1): e28300, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36369641

RESUMO

Against the background of the current COVID-19 infection dynamics with its rapid spread of SARS-CoV-2 variants of concern (VOC), the immunity and the vaccine prevention of healthcare workers (HCWs) against SARS-CoV-2 continues to be of high importance. This observational cross-section study assesses factors influencing the level of anti-SARS-CoV-2-spike IgG after SARS-CoV-2 infection or vaccination. One thousand seven hundred and fifty HCWs were recruited meeting the following inclusion criteria: age ≥18 years, PCR-confirmed SARS-CoV-2 infection convalescence and/or at least one dose of COVID-19 vaccination. anti-SARS-CoV-2-spike IgG titers were determined by SERION ELISA agile SARS-CoV-2 IgG. Mean anti-SARS-CoV-2-spike IgG levels increased significantly by number of COVID-19 vaccinations (92.2 BAU/ml for single, 140.9 BAU/ml for twice and 1144.3 BAU/ml for threefold vaccination). Hybrid COVID-19 immunized respondents (after infection and vaccination) had significantly higher antibody titers compared with convalescent only HCWs. Anti-SARS-CoV-2-spike IgG titers declined significantly with time after the second vaccination. Smoking and high age were associated with lower titers. Both recovered and vaccinated HCWs presented a predominantly good humoral immune response. Smoking and higher age limited the humoral SARS-CoV-2 immunity, adding to the risk of severe infections within this already health impaired collective.


Assuntos
COVID-19 , Humanos , Adolescente , COVID-19/prevenção & controle , Vacinas contra COVID-19 , SARS-CoV-2 , Anticorpos Antivirais , Pessoal de Saúde , Imunoglobulina G
3.
Blood ; 137(22): 3105-3115, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-33827131

RESUMO

Glycoprotein VI (GPVI), the platelet immunoreceptor tyrosine activating motif (ITAM) receptor for collagen, plays a striking role on vascular integrity in animal models of inflammation and sepsis. Understanding ITAM-receptor signaling defects in humans suffering from sepsis may improve our understanding of the pathophysiology, especially during disease onset. In a pilot study, platelets from 15 patients with sepsis were assessed consecutively at day of admission, day 5 to 7, and the day of intensive care unit (ICU) discharge and subjected to comprehensive analyses by flow cytometry, aggregometry, and immunoblotting. Platelet function was markedly reduced in all patients. The defect was most prominent after GPVI stimulation with collagen-related peptide. In 14 of 15 patients, GPVI dysfunction was already present at time of ICU admission, considerably before the critical drop in platelet counts. Sepsis platelets failed to transduce the GPVI-mediated signal to trigger tyrosine phosphorylation of Syk kinase or LAT. GPVI deficiency was partially inducible in platelets of healthy donors through coincubation in whole blood, but not in plasma from patients with sepsis. Platelet aggregation upon GPVI stimulation increased only in those patients whose condition ameliorated. As blunted GPVI signaling occurred early at sepsis onset, this defect could be exploited as an indicator for early sepsis diagnosis, which needs to be confirmed in prospective studies.


Assuntos
Plaquetas/metabolismo , Agregação Plaquetária , Glicoproteínas da Membrana de Plaquetas/metabolismo , Sepse/metabolismo , Transdução de Sinais , Adulto , Idoso , Idoso de 80 Anos ou mais , Plaquetas/patologia , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Sepse/patologia
4.
J Sleep Res ; : e13929, 2023 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-37177872

RESUMO

Sleep modulates the immune response, and sleep loss can reduce vaccine immunogenicity; vice versa, immune responses impact sleep. We aimed to investigate the influence of mental health and sleep quality on the immunogenicity of COVID-19 vaccinations and, conversely, of COVID-19 vaccinations on sleep quality. The prospective CoVacSer study monitored mental health, sleep quality and Anti-SARS-CoV-2-Spike IgG titres in a cohort of 1082 healthcare workers from 29 September 2021 to 19 December 2022. Questionnaires and blood samples were collected before, 14 days, and 3 months after the third COVID-19 vaccination, as well as in 154 participants before and 14 days after the fourth COVID-19 vaccination. Healthcare workers with psychiatric disorders had slightly lower Anti-SARS-CoV-2-Spike IgG levels before the third COVID-19 vaccination. However, this effect was mediated by higher median age and body mass index in this subgroup. Antibody titres following the third and fourth COVID-19 vaccinations ("booster vaccinations") were not significantly different between subgroups with and without psychiatric disorders. Sleep quality did not affect the humoral immunogenicity of the COVID-19 vaccinations. Moreover, the COVID-19 vaccinations did not impact self-reported sleep quality. Our data suggest that in a working population neither mental health nor sleep quality relevantly impact the immunogenicity of COVID-19 vaccinations, and that COVID-19 vaccinations do not cause a sustained deterioration of sleep, suggesting that they are not a precipitating factor for insomnia. The findings from this large-scale real-life cohort study will inform clinical practice regarding the recommendation of COVID-19 booster vaccinations for individuals with mental health and sleep problems.

5.
Clin Oral Investig ; 27(10): 5991-5998, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37603167

RESUMO

OBJECTIVES: Different platelet-rich fibrin (PRF) protocols exist and are known to differ in resulting mechanical and bioactive properties. Centrifugation parameters may also influence drug release, in particular antibiotics, when using PRF as a bio-carrier. We thus evaluated three common protocols regarding effects on the bio-carrier properties. MATERIALS AND METHODS: In a prospective trial comprising 33 patients, we compared different protocols for PRF as a bio-carrier for ampicillin/sulbactam (SAM). Blood samples were taken shortly after a single dose of ampicillin/sulbactam (2 g/1 g) was administered to patients intravenously. PRF was obtained by centrifugation and three protocols were used: protocol A (1300 rpm, 8 min, RCF-max = 208 g), B (2300 rpm, 12 min, RCF-max = 652 g), and C (1500 rpm, 14 min, RCF-max = 276 g). The antibacterial activity of PRF was investigated against five oral species in vitro, based on agar diffusion methodology. RESULTS: The study demonstrates that a single dose of SAM is sufficient to reach high concentrations in PRF in all protocols (150 µg/ml), which is comparable to the plasma SAM concentration. Antibacterial activity was inferred from the diameter of inhibition zones seen in agar diffusion tests using PRF discs. Protocol B resulted in the largest inhibition zones. One-way ANOVA revealed statistically improved results for protocol B for some bacteria. CONCLUSIONS: The study provides valuable data on PRF antibiotic enrichment, notably SAM. A single dose of SAM is sufficient to reach clinically relevant concentrations in PRF. CLINICAL RELEVANCE: These findings potentially extend the application of PRF, for example in patients with osteonecrosis of the jaw or in oral surgery (e.g., stick bone).


Assuntos
Fibrina Rica em Plaquetas , Humanos , Sulbactam/farmacologia , Ágar , Estudos Prospectivos , Peptídeos e Proteínas de Sinalização Intercelular , Centrifugação/métodos , Antibacterianos/farmacologia , Ampicilina/farmacologia
6.
Clin Oral Investig ; 26(12): 7033-7044, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35941396

RESUMO

OBJECTIVES: Mechanisms of wound healing are often impaired in patients with osteonecrosis of the jaw (ONJ). According to the guidelines for the treatment of this disease, early surgical intervention is indicated. However, surgery often faces complications such as wound healing disorders. The application of platelet-rich fibrin (PRF) after necrosectomy between bone and mucosa may constitute a promising approach to improve surgical results. An aspect that was not investigated until now is that PRF acts as a "bio-carrier" for antibiotics previously applied intravenously. MATERIALS AND METHODS: We investigated the antimicrobial properties of PRF in 24 patients presenting ONJ undergoing systemic antibiosis with ampicillin/sulbactam. We measured the concentration of ampicillin/sulbactam in plasma and PRF and performed agar diffusion tests. Ampicillin/sulbactam was applied intravenously to the patient 10 minutes for blood sampling for PRF. No further incorporation of patients' blood or PRF product with antibiotic drugs was obtained. Four healthy patients served as controls. RESULTS: Our results revealed that PRF is highly enriched with ampicillin/sulbactam that is released to the environment. The antibiotic concentration in PRF was comparable to the plasma concentration of ampicillin/sulbactam. The inhibition zone (IZ) of PRF was comparable to the standard ampicillin/sulbactam discs used in sensitivity testing. CONCLUSIONS: The results of our study demonstrated that PRF is a reliable bio-carrier for systemic applied antibiotics and exhibits a large antimicrobial effect. CLINICAL RELEVANCE: We describe a clinically useful feature of PRF as a bio-carrier for antibiotics. Especially when applied to poorly perfused tissues and bone such as in ONJ, the local release of antibiotics can reduce wound healing disorders like infections.


Assuntos
Fibrina Rica em Plaquetas , Humanos , Sulbactam/farmacologia , Ampicilina/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico
7.
J Clin Microbiol ; 59(8): e0031921, 2021 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-33962959

RESUMO

For the control of immunity in COVID-19 survivors and vaccinated subjects, there is an urgent need for reliable and rapid serological assays. Based on samples from 63 COVID-19 survivors up to 7 months after symptom onset, and on 50 serum samples taken before the beginning of the pandemic, we compared the performances of three commercial immunoassays for the detection of SARS-CoV-2 IgA and IgG antibodies (Euroimmun SARS-COV-2 IgA/IgG, Mikrogen recomWell SARS-CoV-2 IgA/IgG, and Serion ELISA agile SARS-CoV-2 IgA/IgG) and three rapid lateral flow (immunochromatographic) tests (Abbott PanBio COVID-19 IgG/IgM, Nadal COVID-19 IgG/IgM, and Cleartest Corona 2019-nCOV IgG/IgM) with a 50% plaque-reduction neutralization test (PRNT50) representing the gold standard. Fifty-seven out of 63 PCR-confirmed COVID-19 patients (90%) showed neutralizing antibodies. The sensitivity of the seven assays ranged from 7.0% to 98.3%, and the specificity ranged from 86.0% to 100.0%. Only one commercial immunoassay showed a sensitivity and specificity of greater than 98%.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Antivirais , Humanos , Imunoensaio , Imunoglobulina M , Pandemias , Sensibilidade e Especificidade
8.
J Antimicrob Chemother ; 76(4): 920-929, 2021 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-33501993

RESUMO

BACKGROUND: Haemophilus influenzae can cause invasive infections, in which cefotaxime is among the first-line antibiotics for treatment. The prevalence of cefotaxime-resistant H. influenzae in Europe is reported to be on a low level. Nevertheless, systematic studies with a large set of invasive isolates are scarce. OBJECTIVES: To provide prevalence data for cefotaxime resistance in invasive H. influenzae isolates in Germany 2016-19 and investigate the epidemiological relevance of PBP3 mutations known to elevate the cefotaxime MIC. METHODS: Cefotaxime susceptibility of invasive H. influenzae isolates, collected in the national laboratory surveillance programme, was examined by gradient agar diffusion (GAD) testing. Cefotaxime resistance was determined according to EUCAST guidelines (resistance breakpoint MIC >0.125 mg/L). Therefore, the MIC for all resistant isolates was verified by broth microdilution method (BMD). WGS was performed to investigate the genetic relationship of cefotaxime-resistant isolates and to analyse alterations in the PBP3. An analysis of the geographic distribution of the resistant isolates was performed. RESULTS: From 2016 to 2019, the German National Reference Laboratory for Meningococci and H. influenzae received 2432 invasive H. influenzae isolates from blood and CSF. According to GAD results, 27 strains were resistant to cefotaxime. BMD confirmed the resistance in 22 of these isolates, which equals a prevalence of cefotaxime resistance of 0.90% in invasive H. influenzae in Germany. Among cefotaxime-resistant isolates cgMLST revealed three clusters. PBP3 analysis showed previously described mutations in our strains. In comparison with cefotaxime-susceptible strains, the alterations L389F and Y557H were significantly associated with cefotaxime resistance, but were not present in all resistant strains. Geographic analysis showed that the disease cases with cefotaxime-resistant H. influenzae were evenly spread throughout the population in Germany. CONCLUSIONS: Cefotaxime is still well suited for the treatment of invasive H. influenzae infections. Rarely occurring cefotaxime resistance is caused by sporadic mutations. The role of PBP3 mutations needs further investigation.


Assuntos
Infecções por Haemophilus , Haemophilus influenzae , Antibacterianos/farmacologia , Cefotaxima/farmacologia , Europa (Continente) , Alemanha/epidemiologia , Infecções por Haemophilus/epidemiologia , Haemophilus influenzae/genética , Humanos , Testes de Sensibilidade Microbiana , Proteínas de Ligação às Penicilinas , Prevalência
9.
J Antimicrob Chemother ; 75(8): 2076-2086, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32449913

RESUMO

BACKGROUND: The carbapenems imipenem and meropenem play an important role in the empirical anti-infective treatment of critically ill patients. Carbapenem resistance in Haemophilus influenzae (Hi) has rarely been reported. OBJECTIVES: We provide prevalence data for resistance to carbapenems from laboratory surveillance of invasive Hi infections in Germany in 2016. METHODS: Phenotypic susceptibility testing against ampicillin, amoxicillin/clavulanate, cefotaxime and imipenem was carried out on 474 isolates from blood and CSF. The isolates were collected as part of the national laboratory surveillance programme. Imipenem-resistant strains were further tested for meropenem susceptibility. Molecular analysis was done by ftsI sequencing to detect mutations in PBP3, by acrR sequencing to detect alterations in the regulatory protein of the AcrAB-TolC efflux pump and by MLST. RESULTS: No resistance to meropenem was detected. Cefotaxime resistance was rare (n = 3; 0.6%). Imipenem resistance was found in 64 strains (13.5%) using gradient agar diffusion and was confirmed in 26 isolates by broth microdilution (5.5%). Imipenem resistance occurred predominantly in Hi that were ß-lactamase negative but ampicillin resistant and in those that were ß-lactamase positive but nevertheless amoxicillin/clavulanate resistant. This finding suggested a ß-lactamase-independent mechanism. Accordingly, sequence analysis of PBP3 identified previously described mutations. MLST of the imipenem-resistant strains, which were all non-typeable Hi, revealed a high diversity. CONCLUSIONS: We conclude that imipenem, but not meropenem, resistance is frequent in Hi. It is likely to be supported by PBP3 mutations.


Assuntos
Infecções por Haemophilus , Imipenem , Antibacterianos/farmacologia , Alemanha/epidemiologia , Infecções por Haemophilus/epidemiologia , Haemophilus influenzae/genética , Humanos , Imipenem/farmacologia , Testes de Sensibilidade Microbiana , Epidemiologia Molecular , Tipagem de Sequências Multilocus , beta-Lactamases
10.
J Antimicrob Chemother ; 75(4): 984-987, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31971241

RESUMO

BACKGROUND: Post-exposure prophylaxis (PEP) for close contacts of invasive meningococcal disease (IMD) cases is recommended in most countries to avoid secondary cases by eradicating supposed meningococcal colonization. Currently, rifampicin, ciprofloxacin and ceftriaxone are recommended in many countries including Germany. Azithromycin has been shown to eradicate meningococcal colonization. OBJECTIVES: To assess the azithromycin susceptibility of invasive Neisseria meningitidis isolates. METHODS: A subset of German invasive meningococcal isolates from 2006-18 was selected for this study. Azithromycin MIC was determined using broth microdilution and agar gradient diffusion. RESULTS: Azithromycin MICs as determined by broth microdilution ranged from <0.003 to 2 mg/L (median 0.50 mg/L, Q75 1 mg/L). All isolates were susceptible to azithromycin according to the CLSI breakpoint (95% CI 0.0%-1.5%). There was no significant correlation between MICs determined by broth microdilution and agar gradient diffusion. Nevertheless, the two methods were consistent regarding the categorization of all isolates as susceptible. CONCLUSIONS: Azithromycin is an eligible antibiotic for PEP of IMD close contacts. It is approved for adults as well as children and may even be used in pregnancy. Because of easier application and lower toxicity, it might be an alternative to rifampicin and ciprofloxacin, as we found no resistant isolates. Since a gonococcal gene associated with elevated azithromycin MICs has been reported in N. meningitidis, careful monitoring of the emergence of resistant strains is nevertheless necessary for meningococci. Lack of concordance of MICs between broth microdilution and agar gradient diffusion needs to be considered.


Assuntos
Azitromicina , Neisseria meningitidis , Adulto , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Azitromicina/farmacologia , Ceftriaxona , Criança , Alemanha , Humanos , Testes de Sensibilidade Microbiana , Neisseria gonorrhoeae , Profilaxia Pós-Exposição
11.
Euro Surveill ; 25(25)2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32613936

RESUMO

IntroductionInvasive meningococcal disease (IMD) is a rare condition with a high case fatality rate. While most patients suffer from one single episode in life, there is anecdotal evidence for recurrent infection.AimThe German National Reference Laboratory for Meningococci and Haemophilus influenzae (NRZMHi) analysed IMD cases from 2002 to 2018 to retrospectively quantify the risk of recurrent infection.MethodsRecurrent IMD was defined as detection of Neisseria meningitidis in a sample of the same patient more than 30 days after the first episode of IMD.ResultsAmong 5,854 patients with a median observation period of 9.4 years, 14 suffered a second IMD episode and one patient a third one. The risk of a recurrent IMD was 29.4 per 100,000 person-years for survivors of the first episode. Rare serogroups (Y, W, E and Z) were more common in patients with recurrent IMD (p < 0.0001).DiscussionPatients surviving IMD were at least at a 50-fold risk of another IMD episode compared with the general population. The study most likely underestimated the risk of recurrent infection. Increased risk may be due to undiagnosed complement deficiencies. The high risk of re-infection argues for vaccination of patients who have survived IMD.


Assuntos
Surtos de Doenças/estatística & dados numéricos , Infecções Meningocócicas/epidemiologia , Neisseria meningitidis/isolamento & purificação , Adolescente , Criança , Pré-Escolar , Feminino , Alemanha/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Infecções Meningocócicas/diagnóstico , Neisseria meningitidis/genética , Técnica de Amplificação ao Acaso de DNA Polimórfico , Estudos Retrospectivos , Fatores de Risco , Sorogrupo , Sorotipagem
12.
Parasitol Res ; 118(6): 1999-2004, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30972570

RESUMO

In the present article, we report on the identification of Vermamoeba (Hartmannella) vermiformis as the etiological agent of a tissue infection close to the eye of a female patient. Laboratory examination revealed no involvement of any pathogenic bacteria or fungi in the tissue infection. V. vermiformis was identified by cultivation and morphology of trophozoites and cysts as well as phylogenetic analysis of nuclear 18S rDNA. The lesion improved in the course of 4 weeks by application of zinc paste.


Assuntos
Amebíase/diagnóstico , Amebíase/patologia , Hartmannella/patogenicidade , Úlcera/parasitologia , Adulto , Amebíase/parasitologia , Animais , DNA de Protozoário/genética , DNA Ribossômico/genética , Feminino , Hartmannella/classificação , Hartmannella/genética , Humanos , Filogenia , Trofozoítos/classificação , Trofozoítos/crescimento & desenvolvimento , Úlcera/patologia
15.
Infection ; 45(5): 607-611, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28429151

RESUMO

PURPOSE: The prevalence of protective anti-diphtheria toxin antibodies decreases with age. Therefore, the elderly might serve as reservoir for potentially toxigenic Corynebacterium (C.) species (C. diphtheriae, C. ulcerans, and C. pseudotuberculosis). This study aimed to examine the colonization rate of the nasopharynx with corynebacteria of individuals aged 65 years and older. METHODS: In the period from October 2012 to June 2013, nasal and throat swabs were taken from 714 asymptomatic subjects aged 65-106 years (average age 77.2) at three regions in Germany and investigated for Corynebacterium species. RESULTS: A total of 402 strains of Corynebacterium species were isolated from 388 out of 714 asymptomatic subjects (carriage rate 54.3%). The carriage rate was significantly higher in study participants living in retirement homes (68.4%) compared to those living autonomously at home (51.1%). Strains were isolated mostly from the nose (99%). Corynebacterium accolens was the most often isolated species (39.8%), followed by C. propinquum (24.1%), C. pseudodiphtheriticum (19.4%), and C. tuberculostearicum (10.2%). No C. diphtheriae, C. ulcerans, and C. pseudotuberculosis strains were isolated. A subsample of 74 subjects was tested serologically for anti-diphtheria antibodies. Protective anti-diphtheria toxin antibodies were found in 29.7% of the subjects; 70.3% showed no protective immunity. CONCLUSIONS: These results suggest that carriage of potentially toxigenic corynebacteria is very rare among people aged 65 and older in Germany. However, the low prevalence of protective anti-diphtheria toxin antibodies might pose a risk for acquiring diphtheria especially for the elderly.


Assuntos
Portador Sadio/epidemiologia , Infecções por Corynebacterium/epidemiologia , Corynebacterium/isolamento & purificação , Doenças Nasofaríngeas/epidemiologia , Nasofaringe/microbiologia , Idoso , Idoso de 80 Anos ou mais , Portador Sadio/microbiologia , Infecções por Corynebacterium/microbiologia , Corynebacterium diphtheriae/isolamento & purificação , Corynebacterium pseudotuberculosis/isolamento & purificação , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Doenças Nasofaríngeas/microbiologia
17.
Int J Med Microbiol ; 305(7): 748-55, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26321008

RESUMO

In this retrospective study covering a four-year observation period (2009-2012) the prevalence of aminopenicillin resistance of invasive Haemophilus influenzae (Hi) in Germany was analyzed. The main resistance mechanism against aminopenicillins is conferred by ß-lactamase production, which can be inhibited by clavulanate or sulbactam. Apart from that, ß-lactamase negative ampicillin resistance (BLNAR) has been reported due to mutations in the penicillin-binding protein PBP3. The prevalence of BLNAR varies considerably in different countries. Representative data from Germany have not been reported. We analyzed 704 culture positive cases with bacteraemia or detection of Hi in cerebrospinal fluid; 82 isolates (11.6%) were phenotypically resistant to ampicillin. Among these isolates, 65 (79.3%) showed ß-lactamase production, and 17 isolates (20.7%) were phenotypic BLNAR Hi. The proportion of ampicillin resistant isolates remained stable over the observation period. Analysis of the PBP3 sequences of 133 isolates with different susceptibility phenotypes including susceptible, BLNAR, and ß-lactamase positive isolates, revealed a high genetic diversity. Previously described PBP3 mutations were associated to elevated MIC values, albeit not exclusively, since few highly susceptible strains were found to be positive for the mutations. Furthermore, since ampicillin susceptible strains with elevated MIC values frequently harboured these mutations, prediction of the resistance phenotype using ftsI sequencing appears to be impossible.


Assuntos
Resistência a Ampicilina , Ampicilina/farmacologia , Antibacterianos/farmacologia , Infecções por Haemophilus/microbiologia , Haemophilus influenzae/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Criança , Pré-Escolar , Feminino , Genótipo , Alemanha/epidemiologia , Infecções por Haemophilus/epidemiologia , Haemophilus influenzae/isolamento & purificação , Humanos , Lactente , Recém-Nascido , Masculino , Meningites Bacterianas/epidemiologia , Meningites Bacterianas/microbiologia , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Proteínas de Ligação às Penicilinas/genética , Prevalência , Estudos Retrospectivos , Adulto Jovem , beta-Lactamases/genética
18.
JAC Antimicrob Resist ; 6(1): dlad148, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38161964

RESUMO

Background: Haemophilus influenzae (Hi) is a Gram-negative bacterium that may cause sepsis or meningitis, treatment of which mainly includes ß-lactam antibiotics. Since 2019 EUCAST breakpoints for piperacillin/tazobactam have been available. Little is known about the prevalence and mechanisms of piperacillin/tazobactam resistance in Hi. Objectives: To provide reliable prevalence data for piperacillin/tazobactam resistance in Hi in Germany, to evaluate different antibiotic susceptibility testing methods and to examine possible resistance mechanisms. Methods: According to EUCAST breakpoints, the MIC for piperacillin/tazobactam resistance is >0.25 mg/L. All invasive Hi in Germany from 2019 were examined by gradient agar diffusion (GAD) for piperacillin/tazobactam susceptibility. Piperacillin/tazobactam broth microdilution (BMD), piperacillin GAD on tazobactam-containing agar [piperacillin GAD on Mueller-Hinton agar with horse blood (MH-F)/tazobactam) and piperacillin/tazobactam agar dilution (AD) were used for confirmation. Phenotypic testing was complemented by ftsI sequencing. Results: Piperacillin/tazobactam GAD resulted in 2.9% (21/726) resistant Hi. BMD did not confirm piperacillin/tazobactam resistance. Two strains were found resistant by AD, of which one was also resistant using piperacillin GAD on MH-F/tazobactam. Overall, we found two strains with a piperacillin/tazobactam MIC >0.25 mg/L in at least two different tests (0.3%). Both were ß-lactamase-producing amoxicillin/clavulanate-resistant with PBP3 mutations characterized as group III-like+. Relevant PBP3 mutations occurred in six strains without phenotypic piperacillin/tazobactam resistance. These mutations suggest a reduced efficacy of ß-lactam antibiotics in these isolates. Conclusions: Piperacillin/tazobactam resistance prevalence in invasive Hi is low in Germany. Reduced susceptibility was correlated with PBP3 mutations, in particular with group III mutations.

19.
J Craniomaxillofac Surg ; 52(3): 355-362, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38368214

RESUMO

The aim of this study was to investigate the jawbone concentration of clindamycin (CLI) in patients with an osteonecrosis of the jaw (ONJ). Patients with medication-related ONJ (MRONJ) and osteoradionecrosis (ORN) with an antibiotic treatment with CLI were included. Plasma, vital and necrotic bone samples were collected. Plasma and jawbone samples were analyzed by liquid chromatography-tandem mass spectrometry. Patients with MRONJ exhibited a mean plasma CLI concentration of 9.6 µg/mL (SD ± 3.6 µg/mL) and mean concentrations of 2.3 µg/g CLI (SD ± 1.4 µg/g) and 2.1 µg/g CLI (SD ± 2.4 µg/g) in vital and necrotic bone samples, without statistical significance (p = 0.79). In patients with ORN, mean concentration in plasma was 12.0 µg/mL (SD ± 2.6 µg/mL), in vital bone 2.1 µg/g (SD ± 1.5 µg/g), and in necrotic bone 1.7 µg/g (SD ± 1.2 µg/g). Vital and necrotic bone concentrations did not differ significantly (p = 0.88). The results demonstrate that CLI concentrations are considerably lower than in plasma, but sufficient for most bacteria present in ONJ. Within the limitations of the study, it seems that CLI is a relevant alternative to other antibiotics in the treatment of ONJ because it reaches adequate concentrations in jawbone.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Osteonecrose , Osteorradionecrose , Humanos , Clindamicina/uso terapêutico , Estudos Prospectivos , Osteonecrose/induzido quimicamente , Osteorradionecrose/etiologia , Arcada Osseodentária , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Difosfonatos
20.
Dtsch Arztebl Int ; 121(4): 114-120, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38229497

RESUMO

BACKGROUND: In late 2022, health care institutions in Germany reported an unusual number of severe, invasive bacterial infections in association with a high incidence of viral respiratory infections. METHODS: We analyzed routine data on invasive infections due to Haemophilus influenzae, Neisseria meningitidis, Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus pyogenes (2017-2023) from a voluntary, laboratory-based surveillance system involving continuously participating facilities providing diagnostic routine data that cover approximately one-third of the German population. RESULTS: In the first quarter (Q1) of 2023, the number of invasive S. pyogenes isolates rose by 142% (n = 837 vs. mean Q1/2017-2019 = 346, 95% CI [258; 434]), while the number of H. influenzae isolates rose by 90% (n = 209 in Q1/2023 vs. mean Q1/2017-2019 = 110, 95% CI [79; 142]), compared to pre-pandemic seasonal peak values. The number of invasive S. pneumoniae isolates was high in two quarters (n = 1732 in Q4/2022 und Q1/2023). Adults aged 55 and older and children younger than 5 years were most affected by invasive H. influenzae, S. pneumoniae, and S. pyogenes infections. N. meningitidis was most commonly found in children under age 5. CONCLUSION: The reason for the marked rise in invasive bacterial infections may be an increased circulation of respiratory pathogens and elevated susceptibility in the population after relaxation of the measures taken to prevent COVID-19 infection. Coinfections with respiratory viruses may have reinforced this effect. We recommend continuous surveillance, preventive measures such as raising awareness about invasive bacterial diseases, and vaccination as recommended by the German Standing Committee on Vaccinations (STIKO).


Assuntos
Infecções Bacterianas , Neisseria meningitidis , Infecções Respiratórias , Infecções Estafilocócicas , Adulto , Criança , Humanos , Infecções Bacterianas/epidemiologia , Streptococcus pneumoniae , Haemophilus influenzae , Streptococcus pyogenes , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/microbiologia , Antibacterianos
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