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1.
Acta Ortop Mex ; 38(3): 172-178, 2024.
Artigo em Espanhol | MEDLINE | ID: mdl-38862147

RESUMO

INTRODUCTION: intravenous antibiotic prophylaxis has significantly reduced the incidence of periprosthetic joint infection (PJI) in knee surgeries. However, for patients colonized with methicillin-resistant Staphylococcus aureus (MRSA) or those at risk of colonization, prophylaxis should include vancomycin. Intraosseous (IO) administration of vancomycin could enhance its effectiveness in total knee arthroplasty (TKA). MATERIAL AND METHODS: a retrospective review was conducted, including 143 patients at risk of PJI scheduled for TKA who received IO vancomycin along with intravenous (IV) cefazolin, referred to as group I (GI), between May 2021 and December 2022. The occurrence of complications in the first three postoperative months was evaluated. Results were compared with 140 patients without risk factors who received standard IV prophylaxis, designated as group II (GII). RESULTS: in GI, 500 mg of IO vancomycin was administered, injected into the proximal tibia, in addition to standard IV prophylaxis. In GII, patients received only IV cefazolin. The incidence of complications was 1.64% in GI and 1.4% in GII. The PJI rate at 90 postoperative days was 0.69% in GI and 0.71% in GII. CONCLUSIONS: IO vancomycin administration, along with standard IV prophylaxis, provides a safe and effective alternative for patients at risk of MRSA colonization. This approach minimizes complications associated with IV vancomycin use and addresses logistical challenges of timely administration.


INTRODUCCIÓN: la profilaxis antibiótica intravenosa ha reducido significativamente la incidencia de infección articular periprotésica (IAP) en cirugías de rodilla. No obstante, para pacientes colonizados con Staphylococcus aureus resistente a meticilina (SARM) o aquellos con riesgo de colonización, la profilaxis debe incluir vancomicina. La administración intraósea de vancomicina podría potenciar su efectividad en la artroplastía total de rodilla. MATERIAL Y MÉTODOS: se realizó una revisión retrospectiva que incluyó a 143 pacientes en riesgo de IAP programados para artroplastía total de rodilla que recibieron vancomicina intraósea junto a cefazolina intravenosa (IV), a quienes denominamos grupo I (GI), entre mayo de 2021 y diciembre de 2022. Se evaluó la aparición de complicaciones en los primeros tres meses postoperatorios. Los resultados se compararon con 140 pacientes sin factores de riesgo que recibieron profilaxis intravenosa estándar, denominados grupo II (GII). RESULTADOS: en el GI, se administraron 500 mg de vancomicina intraósea, inyectados en la tibia proximal, además de la profilaxis intravenosa estándar. En el GII, los pacientes recibieron sólo cefazolina intravenosa. La incidencia de complicaciones fue de 1.64% en el GI y de 1.4% en el GII. La tasa de IAP a los 90 días postoperatorios fue de 0.69% en el GI y de 0.71% en el GII. CONCLUSIONES: la administración de vancomicina intraósea, junto con la profilaxis intravenosa estándar, ofrece una alternativa segura y eficaz para pacientes con riesgo de colonización por SARM. Este enfoque minimiza las complicaciones asociadas con el uso intravenoso de vancomicina y soluciona los desafíos logísticos de la administración oportuna.


Assuntos
Antibacterianos , Antibioticoprofilaxia , Artroplastia do Joelho , Cefazolina , Infecções Relacionadas à Prótese , Vancomicina , Humanos , Vancomicina/administração & dosagem , Vancomicina/uso terapêutico , Estudos Retrospectivos , Artroplastia do Joelho/efeitos adversos , Masculino , Feminino , Idoso , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Pessoa de Meia-Idade , Infecções Relacionadas à Prótese/prevenção & controle , Infecções Relacionadas à Prótese/etiologia , Cefazolina/administração & dosagem , Cefazolina/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infusões Intraósseas , Idoso de 80 Anos ou mais , Infecções Estafilocócicas/prevenção & controle
2.
Hum Vaccin Immunother ; 20(1): 2360338, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38857905

RESUMO

Staphylococcal Enterotoxin B (SEB), produced by Staphylococcus aureus (S. aureus), is a powerful superantigen that induces severe immune disruption and toxic shock syndrome (TSS) upon binding to MHC-II and TCR. Despite its significant impact on the pathogenesis of S. aureus, there are currently no specific therapeutic interventions available to counteract the mechanism of action exerted by this toxin. In this study, we have identified a human monoclonal antibody, named Hm0487, that specifically targets SEB by single-cell sequencing using PBMCs isolated from volunteers enrolled in a phase I clinical trial of the five-antigen S. aureus vaccine. X-ray crystallography studies revealed that Hm0487 exhibits high affinity for a linear B cell epitope in SEB (SEB138-147), which is located distantly from the site involved in the formation of the MHC-SEB-TCR ternary complex. Furthermore, in vitro studies demonstrated that Hm0487 significantly impacts the interaction of SEB with both receptors and the binding to immune cells, probably due to an allosteric effect on SEB rather than competing with receptors for binding sites. Moreover, both in vitro and in vivo studies validated that Hm0487 displayed efficient neutralizing efficacy in models of lethal shock and sepsis induced by either SEB or bacterial challenge. Our findings unveil an alternative mechanism for neutralizing the pathogenesis of SEB by Hm0487, and this antibody provides a novel strategy for mitigating both SEB-induced toxicity and S. aureus infection.


Assuntos
Anticorpos Monoclonais , Anticorpos Neutralizantes , Enterotoxinas , Enterotoxinas/imunologia , Enterotoxinas/antagonistas & inibidores , Humanos , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Animais , Cristalografia por Raios X , Staphylococcus aureus/imunologia , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/prevenção & controle , Epitopos de Linfócito B/imunologia , Camundongos , Choque Séptico/imunologia , Choque Séptico/prevenção & controle , Feminino , Leucócitos Mononucleares/imunologia , Vacinas Antiestafilocócicas/imunologia , Anticorpos Antibacterianos/imunologia , Superantígenos/imunologia
4.
Bone Joint J ; 106-B(6): 632-638, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38821510

RESUMO

Aims: Delayed postoperative inoculation of orthopaedic implants with persistent wound drainage or bacterial seeding of a haematoma can result in periprosthetic joint infection (PJI). The aim of this in vivo study was to compare the efficacy of vancomycin powder with vancomycin-eluting calcium sulphate beads in preventing PJI due to delayed inoculation. Methods: A mouse model of PJI of the knee was used. Mice were randomized into groups with intervention at the time of surgery (postoperative day (POD) 0): a sterile control (SC; n = 6); infected control (IC; n = 15); systemic vancomycin (SV; n = 9); vancomycin powder (VP; n = 21); and vancomycin bead (VB; n = 19) groups. Delayed inoculation was introduced during an arthrotomy on POD 7 with 1 × 105 colony-forming units (CFUs) of a bioluminescent strain of Staphylococcus aureus. The bacterial burden was monitored using bioluminescence in vivo. All mice were killed on POD 21. Implants and soft-tissue were harvested and sonicated for analysis of the CFUs. Results: The mean in vivo bioluminescence in the VB group was significantly lower on POD 8 and POD 10 compared with the other groups. There was a significant 1.3-log10 (95%) and 1.5-log10 (97%) reduction in mean soft-tissue CFUs in the VB group compared with the VP and IC groups (3.6 × 103 vs 7.0 × 104; p = 0.022; 3.6 × 103 vs 1.0 × 105; p = 0.007, respectively) at POD 21. There was a significant 1.6-log10 (98%) reduction in mean implant CFUs in the VB group compared with the IC group (1.3 × 100 vs 4.7 × 101, respectively; p = 0.038). Combined soft-tissue and implant infection was prevented in 10 of 19 mice (53%) in the VB group as opposed to 5 of 21 (24%) in the VP group, 3 of 15 (20%) in the IC group, and 0% in the SV group. Conclusion: In our in vivo mouse model, antibiotic-releasing calcium sulphate beads appeared to outperform vancomycin powder alone in lowering the bacterial burden and preventing soft-tissue and implant infections.


Assuntos
Antibacterianos , Sulfato de Cálcio , Modelos Animais de Doenças , Infecções Relacionadas à Prótese , Infecções Estafilocócicas , Vancomicina , Animais , Infecções Relacionadas à Prótese/prevenção & controle , Infecções Relacionadas à Prótese/microbiologia , Camundongos , Vancomicina/administração & dosagem , Antibacterianos/administração & dosagem , Infecções Estafilocócicas/prevenção & controle , Carga Bacteriana/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Distribuição Aleatória , Prótese do Joelho/efeitos adversos , Feminino
5.
ACS Appl Mater Interfaces ; 16(19): 24421-24430, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38690964

RESUMO

Periprosthetic infections caused by Staphylococcus aureus (S. aureus) pose unique challenges in orthopedic surgeries, in part due to the bacterium's capacity to invade surrounding bone tissues besides forming recalcitrant biofilms on implant surfaces. We previously developed prophylactic implant coatings for the on-demand release of vancomycin, triggered by the cleavage of an oligonucleotide (Oligo) linker by micrococcal nuclease (MN) secreted by the Gram-positive bacterium, to eradicate S. aureus surrounding the implant in vitro and in vivo. Building upon this coating platform, here we explore the feasibility of extending the on-demand release to ampicillin, a broad-spectrum aminopenicillin ß-lactam antibiotic that is more effective than vancomycin in killing Gram-negative bacteria that may accompany S. aureus infections. The amino group of ampicillin was successfully conjugated to the carboxyl end of an MN-sensitive Oligo covalently integrated in a polymethacrylate hydrogel coating applied to titanium alloy pins. The resultant Oligo-Ampicillin hydrogel coating released the ß-lactam in the presence of S. aureus and successfully cleared nearby S. aureus in vitro. When the Oligo-Ampicillin-coated pin was delivered to a rat femoral canal inoculated with 1000 cfu S. aureus, it prevented periprosthetic infection with timely on-demand drug release. The clearance of the bacteria from the pin surface as well as surrounding tissue persisted over 3 months, with no local or systemic toxicity observed with the coating. The negatively charged Oligo fragment attached to ampicillin upon cleavage from the coating did diminish the antibiotic's potency against S. aureus and Escherichia coli (E. coli) to varying degrees, likely due to electrostatic repulsion by the anionic surfaces of the bacteria. Although the on-demand release of the ß-lactam led to adequate killing of S. aureus but not E. coli in the presence of a mixture of the bacteria, strong inhibition of the colonization of the remaining E. coli on hydrogel coating was observed. These findings will inspire considerations of alternative broad-spectrum antibiotics, optimized drug conjugation, and Oligo linker engineering for more effective protection against polymicrobial periprosthetic infections.


Assuntos
Ampicilina , Antibacterianos , Materiais Revestidos Biocompatíveis , Infecções Relacionadas à Prótese , Infecções Estafilocócicas , Staphylococcus aureus , Animais , Staphylococcus aureus/efeitos dos fármacos , Ampicilina/química , Ampicilina/farmacologia , Ratos , Antibacterianos/química , Antibacterianos/farmacologia , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Infecções Estafilocócicas/prevenção & controle , Infecções Estafilocócicas/tratamento farmacológico , Infecções Relacionadas à Prótese/prevenção & controle , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Relacionadas à Prótese/microbiologia , Ratos Sprague-Dawley , Testes de Sensibilidade Microbiana , Liberação Controlada de Fármacos , Próteses e Implantes
6.
ACS Appl Bio Mater ; 7(5): 3086-3095, 2024 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-38652779

RESUMO

Of the 27 million surgeries performed in the United States each year, a reported 2.6% result in a surgical site infection (SSI), and Staphylococci species are commonly the culprit. Alternative therapies, such as nitric oxide (NO)-releasing biomaterials, are being developed to address this issue. NO is a potent antimicrobial agent with several modes of action, including oxidative and nitrosative damage, disruption of bacterial membranes, and dispersion of biofilms. For targeted antibacterial effects, NO is delivered by exogenous donor molecules, like S-nitroso-N-acetylpenicillamine (SNAP). Herein, the impregnation of SNAP into poly(lactic-co-glycolic acid) (PLGA) for SSI prevention is reported for the first time. The NO-releasing PLGA copolymer is fabricated and characterized by donor molecule loading, leaching, and the amount remaining after ethylene oxide sterilization. The swelling ratio, water uptake, static water contact angle, and tensile strength are also investigated. Furthermore, its cytocompatibility is tested against 3T3 mouse fibroblast cells, and its antimicrobial efficacy is assessed against multiple Staphylococci strains. Overall, the NO-releasing PLGA copolymer holds promise as a suture material for eradicating surgical site infections caused by Staphylococci strains. SNAP impregnation affords robust antibacterial properties while maintaining the cytocompatibility and mechanical integrity.


Assuntos
Antibacterianos , Materiais Biocompatíveis , Teste de Materiais , Óxido Nítrico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Infecção da Ferida Cirúrgica , Suturas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecção da Ferida Cirúrgica/microbiologia , Óxido Nítrico/química , Óxido Nítrico/metabolismo , Camundongos , Antibacterianos/farmacologia , Antibacterianos/química , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/prevenção & controle , Tamanho da Partícula , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus/efeitos dos fármacos
7.
Immunol Cell Biol ; 102(5): 365-380, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38572664

RESUMO

Staphylococcus aureus is a significant bacterial pathogen in both community and hospital settings, and the escalation of antimicrobial-resistant strains is of immense global concern. Vaccination is an inviting long-term strategy to curb staphylococcal disease, but identification of an effective vaccine has proved to be challenging. Three well-characterized, ubiquitous, secreted immune evasion factors from the staphylococcal superantigen-like (SSL) protein family were selected for the development of a vaccine. Wild-type SSL3, 7 and 11, which inhibit signaling through Toll-like receptor 2, cleavage of complement component 5 and neutrophil function, respectively, were successfully combined into a stable, active fusion protein (PolySSL7311). Vaccination of mice with an attenuated form of the PolySSL7311 protein stimulated significantly elevated specific immunoglobulin G and splenocyte proliferation responses to each component relative to adjuvant-only controls. Vaccination with PolySSL7311, but not a mixture of the individual proteins, led to a > 102 reduction in S. aureus tissue burden compared with controls after peritoneal challenge. Comparable antibody responses were elicited after coadministration of the vaccine in either AddaVax (an analog of MF59) or an Alum-based adjuvant; but only AddaVax conferred a significant reduction in bacterial load, aligning with other studies that suggest both cellular and humoral immune responses are necessary for protective immunity to S. aureus. Anti-sera from mice immunized with PolySSL7311, but not individual proteins, partially neutralized the functional activities of SSL7. This study confirms the importance of these SSLs for the survival of S. aureus in vivo and suggests that PolySSL7311 is a promising vaccine candidate.


Assuntos
Proteínas de Bactérias , Infecções Estafilocócicas , Vacinas Antiestafilocócicas , Staphylococcus aureus , Superantígenos , Animais , Staphylococcus aureus/imunologia , Vacinas Antiestafilocócicas/imunologia , Superantígenos/imunologia , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/prevenção & controle , Camundongos , Proteínas de Bactérias/imunologia , Anticorpos Antibacterianos/imunologia , Anticorpos Antibacterianos/sangue , Feminino , Proteínas Recombinantes de Fusão/imunologia , Imunoglobulina G/imunologia , Imunoglobulina G/sangue , Estudos de Viabilidade , Vacinação , Antígenos de Bactérias/imunologia , Camundongos Endogâmicos BALB C , Adjuvantes Imunológicos
8.
Biomed Res Int ; 2024: 5675786, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38623471

RESUMO

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of morbidity and mortality among neonates admitted to neonatal intensive care units (NICUs). The MRSA colonization of neonates, attributed to various sources, including mothers, healthcare workers, and environmental surfaces, can lead to severe infection, prolonged hospital stays, and even death, imposing substantial economic burdens. Given the pressing need to mitigate MRSA spread in these vulnerable environments, further examination of the subject is warranted. This systematic review is aimed at synthesizing available evidence on MRSA carriage proportions among mothers of newborns, healthcare workers, and environmental surfaces in NICUs. Methodology. We included observational studies published in English or French from database inception to March 21, 2023. These studies focused on MRSA in nonoutbreak NICU settings, encompassing healthy neonate mothers and healthcare workers, and environmental surfaces. Literature search involved systematic scanning of databases, including Medline, Embase, Web of Science, Global Health, and Global Index Medicus. The quality of the selected studies was assessed using the Hoy et al. critical appraisal scale. The extracted data were summarized to calculate the pooled proportion of MRSA positives, with a 95% confidence interval (CI) based on the DerSimonian and Laird random-effects model. Results: A total of 1891 articles were retrieved from which 16 studies were selected for inclusion. Most of the studies were from high-income countries. The pooled proportion of MRSA carriage among 821 neonate mothers across four countries was found to be 2.1% (95% CI: 0.3-5.1; I2 = 76.6%, 95% CI: 36.1-91.5). The proportion of MRSA carriage among 909 HCWs in eight countries was determined to be 9.5% (95% CI: 3.1-18.4; I2 = 91.7%, 95% CI: 87.1-94.6). The proportion of MRSA carriage among HCWs was highest in the Western Pacific Region, at 50.00% (95% CI: 23.71-76.29). In environmental specimens from five countries, a pooled proportion of 16.6% (95% CI: 3.5-36.0; I2 = 97.7%, 95% CI: 96.6-98.4) was found to be MRSA-positive. Conclusion: With a significant heterogeneity, our systematic review found high MRSA carriage rates in neonate mothers, healthcare workers, and across various environmental surfaces in NICUs, posing a potential risk of nosocomial infections. Urgent interventions, including regular screening and decolonization of MRSA carriers, reinforcing infection control measures, and enhancing cleaning and disinfection procedures within NICUs, are crucial. This trial is registered with CRD42023407114.


Assuntos
Infecção Hospitalar , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/prevenção & controle , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Pessoal de Saúde , Portador Sadio/prevenção & controle
9.
JPEN J Parenter Enteral Nutr ; 48(4): 486-494, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38605559

RESUMO

BACKGROUND: Children with chronic IF require long-term home parenteral nutrition (HPN), administered through a central venous catheter. Catheter-related bloodstream infection (CRBSI) with Staphylococcus aureus is known to be a serious infection with a high mortality rate and risk of complications. A standardized protocol on the management of S aureus CRBSIs in children receiving HPN is lacking. The aim of this study is to evaluate the effectiveness and safety of the current management in an HPN expertise center in the Netherlands. METHODS: We performed a retrospective descriptive cohort study between 2013 and 2022 on children 0-18 years of age with chronic IF requiring long-term HPN. Our primary outcomes were the incidence of S aureus CRBSI per 1000 catheter days, catheter salvage attempt rate, and successful catheter salvage rate. Our secondary outcomes included complications and mortality. RESULTS: A total of 74 patients (39 male; 53%) were included, covering 327.8 catheter years. Twenty-eight patients (38%) had a total of 52 S aureus CRBSIs, with an incidence rate of 0.4 per 1000 catheter days. The catheter salvage attempt rate was 44% (23/52). The successful catheter salvage rate was 100%. No relapse occurred, and no removal was needed after catheter salvage. All complications that occurred were already present at admission before the decision to remove the catheter or not. No patients died because of an S aureus CRBSI. CONCLUSION: Catheter salvage in S aureus CRBSIs in children receiving HPN can be attempted after careful consideration by a multidisciplinary team in an HPN expertise center.


Assuntos
Infecções Relacionadas a Cateter , Insuficiência Intestinal , Nutrição Parenteral no Domicílio , Infecções Estafilocócicas , Staphylococcus aureus , Taurina/análogos & derivados , Tiadiazinas , Humanos , Nutrição Parenteral no Domicílio/métodos , Nutrição Parenteral no Domicílio/efeitos adversos , Masculino , Infecções Relacionadas a Cateter/prevenção & controle , Infecções Relacionadas a Cateter/microbiologia , Infecções Relacionadas a Cateter/epidemiologia , Estudos Retrospectivos , Feminino , Criança , Pré-Escolar , Lactente , Infecções Estafilocócicas/prevenção & controle , Adolescente , Países Baixos , Insuficiência Intestinal/terapia , Recém-Nascido , Cateteres Venosos Centrais/efeitos adversos , Cateteres Venosos Centrais/microbiologia , Doença Crônica , Incidência , Remoção de Dispositivo , Estudos de Coortes , Cateterismo Venoso Central/efeitos adversos , Cateteres de Demora/efeitos adversos , Cateteres de Demora/microbiologia , Bacteriemia/prevenção & controle , Bacteriemia/epidemiologia , Bacteriemia/etiologia
10.
Nat Commun ; 15(1): 3420, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658531

RESUMO

Poly-ß-(1-6)-N-acetylglucosamine (PNAG) is an important vaccine target, expressed on many pathogens. A critical hurdle in developing PNAG based vaccine is that the impacts of the number and the position of free amine vs N-acetylation on its antigenicity are not well understood. In this work, a divergent strategy is developed to synthesize a comprehensive library of 32 PNAG pentasaccharides. This library enables the identification of PNAG sequences with specific patterns of free amines as epitopes for vaccines against Staphylococcus aureus (S. aureus), an important human pathogen. Active vaccination with the conjugate of discovered PNAG epitope with mutant bacteriophage Qß as a vaccine carrier as well as passive vaccination with diluted rabbit antisera provides mice with near complete protection against infections by S. aureus including methicillin-resistant S. aureus (MRSA). Thus, the comprehensive PNAG pentasaccharide library is an exciting tool to empower the design of next generation vaccines.


Assuntos
Infecções Estafilocócicas , Staphylococcus aureus , Animais , Infecções Estafilocócicas/prevenção & controle , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Camundongos , Staphylococcus aureus/imunologia , Coelhos , Vacinas Antiestafilocócicas/imunologia , Vacinas Antiestafilocócicas/administração & dosagem , Feminino , Staphylococcus aureus Resistente à Meticilina/imunologia , Acetilglucosamina/imunologia , Humanos , Epitopos/imunologia , Camundongos Endogâmicos BALB C
11.
Am J Infect Control ; 52(7): 785-789, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38551523

RESUMO

BACKGROUND: Surgical site infection (SSI) is a frequent health care-associated infection. We aimed to reduce SSI risk after joint arthroplasty and spine surgery by reducing Staphylococcus aureus colonization burden with presurgery intranasal povidone-iodine (PVP-I) application in conjunction with skin antisepsis ("the intervention"). METHODS: Retrospective case-control study; postintervention cohort versus a historical cohort. Adults who underwent joint arthroplasty or spine surgery during February 2018 through October 2021 ("post-intervention cohort") included. In the analysis cases any patient who underwent surgery and developed SSI within 90 days postsurgery, controls had no SSI. Postintervention cohort data were compared with a similar retrospective 2016 to 2017 patient cohort that did not use intranasal PVP-I. RESULTS: The postintervention cohort comprised 688 consecutive patients aged 65y/o, 48.8% male, 28 cases, and 660 controls. Relatively more cases than controls had diabetes mellitus (P = .019). There was a 39.6% eradication rate of S aureus nasal colonization post intranasal PVP-I (P < .0001). SSI rate was higher in patients positive versus those negative for S aureus on a 24-hour postsurgery nasal culture (P < .0001). The deep SSI rate per 100 operations postintervention versus the historical cohort decreased for all surgical procedures. CONCLUSIONS: Semiquantitative S aureus nasal colony reduction using intranasal PVP-I is effective for decreasing SSI rate in joint arthroplasty and spine surgery. In patients with presurgery S aureus nasal colonization additional intranasal PVP-I postsurgery application should be considered.


Assuntos
Povidona-Iodo , Infecções Estafilocócicas , Staphylococcus aureus , Infecção da Ferida Cirúrgica , Humanos , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Masculino , Idoso , Feminino , Estudos Retrospectivos , Infecções Estafilocócicas/prevenção & controle , Infecções Estafilocócicas/microbiologia , Estudos de Casos e Controles , Pessoa de Meia-Idade , Povidona-Iodo/administração & dosagem , Procedimentos Ortopédicos/efeitos adversos , Nariz/microbiologia , Idoso de 80 Anos ou mais , Anti-Infecciosos Locais/administração & dosagem , Administração Intranasal
12.
Lancet Microbe ; 5(6): e606-e618, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38518792

RESUMO

Staphylococcus aureus is a leading cause of death by infectious diseases worldwide. Treatment of S aureus infections is difficult due to widespread antibiotic resistance, necessitating alternative approaches and measures for prevention of infection. Because S aureus infections commonly arise from asymptomatic colonisation, decolonisation is considered a key approach for their prevention. Current decolonisation procedures include antibiotic-based and antiseptic-based eradication of S aureus from the nose and skin. However, despite the widespread implementation and partial success of such measures, S aureus infection rates remain worrisome, and resistance to decolonisation agents is on the rise. In this Review we outline the epidemiology and mechanisms of S aureus colonisation, describe how colonisation underlies infection, and discuss current and novel approaches for S aureus decolonisation, with a focus on the latest findings on probiotic strategies and the intestinal S aureus colonisation site.


Assuntos
Antibacterianos , Portador Sadio , Infecções Estafilocócicas , Staphylococcus aureus , Humanos , Infecções Estafilocócicas/prevenção & controle , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Portador Sadio/tratamento farmacológico , Probióticos/uso terapêutico
13.
Curr Opin Infect Dis ; 37(3): 220-225, 2024 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-38545833

RESUMO

PURPOSE OF REVIEW: With cochlear implantation becoming increasingly performed worldwide, an understanding of the risk factors, preventive measures, and management of cochlear implant (CI) infection remains important given the significant morbidity and cost it conveys. RECENT FINDINGS: At the turn of the 21st century there was a decrease in rates of CI infection, particularly meningitis, following the discontinuation of positioner use for CI. However, in more recent years rates of CI infection have remained largely static. Recently, studies evaluating preventive measures such as pneumococcal vaccination, S. aureus decolonization and surgical antibiotic prophylaxis have emerged in the literature. SUMMARY: Prompt recognition of CI infection and appropriate investigation and management are key, however at present treatment is largely informed by cohort and case-control studies and expert opinion. Preventive measures including pneumococcal vaccination, S. aureus decolonization and preoperative antibiotic prophylaxis play a role in reducing rates of CI infection. However, there remains a need for well designed clinical trials to provide higher level evidence to better guide preventive measures for, and management decisions of, CI infections in the future.


Assuntos
Implantes Cocleares , Infecções Relacionadas à Prótese , Humanos , Implantes Cocleares/efeitos adversos , Implantes Cocleares/microbiologia , Fatores de Risco , Infecções Relacionadas à Prótese/prevenção & controle , Antibioticoprofilaxia/métodos , Implante Coclear/efeitos adversos , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Vacinas Pneumocócicas/administração & dosagem , Infecções Estafilocócicas/prevenção & controle
14.
Nat Microbiol ; 9(3): 801-813, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38443581

RESUMO

Staphylococcus aureus is a Gram-positive pathogen responsible for antibiotic-resistant infections. To identify vulnerabilities in cell envelope biogenesis that may overcome resistance, we enriched for S. aureus transposon mutants with defects in cell surface integrity or cell division by sorting for cells that stain with propidium iodide or have increased light-scattering properties, respectively. Transposon sequencing of the sorted populations identified more than 20 previously uncharacterized factors impacting these processes. Cells inactivated for one of these proteins, factor preventing extra Z-rings (FacZ, SAOUHSC_01855), showed aberrant membrane invaginations and multiple FtsZ cytokinetic rings. These phenotypes were suppressed in mutants lacking the conserved cell-division protein GpsB, which forms an interaction hub bridging envelope biogenesis factors with the cytokinetic ring in S. aureus. FacZ was found to interact directly with GpsB in vitro and in vivo. We therefore propose that FacZ is an envelope biogenesis factor that antagonizes GpsB function to prevent aberrant division events in S. aureus.


Assuntos
Infecções Estafilocócicas , Staphylococcus aureus , Humanos , Staphylococcus aureus/genética , Infecções Estafilocócicas/prevenção & controle , Divisão Celular , Membrana Celular , Movimento Celular
15.
Res Vet Sci ; 171: 105202, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38492279

RESUMO

First generation cephalosporins such cephalothin of cefazolin are indicated for antimicrobial prophylaxis for clean and clean contaminated surgical procedures because its antimicrobial spectrum, relative low toxicity and cost. Anesthesia and surgery could alter the pharmacokinetic behavior of different drugs administered perioperative by many mechanisms that affect distribution, metabolism or excretion processes. Intravenous administration of the antimicrobial within 30 and 60 min before incision is recommended in order to reach therapeutic serum and tissue concentrations and redosing is recommended if the duration of the procedure exceeds two half-life of the antimicrobial. To the author's knowledge there are no pharmacokinetic studies of cephalothin in dogs under anesthesia/surgery conditions. The aim of this study was (1) to evaluate the pharmacokinetics of cephalothin in anesthetized dogs undergoing ovariohysterectomy by a nonlinear mixed-effects model and to determine the effect of anesthesia/surgery and other individual covariates on its pharmacokinetic behavior; (2) to determine the MIC and conduct a pharmacodynamic modeling of time kill curves assay of cephalothin against isolates of Staphylococcus spp. isolated from the skin of dogs; (3) to conduct a PK/PD analysis by integration of the obtained nonlinear mixed-effects models in order to evaluate the antimicrobial effect of changing concentrations on simulated bacterial count; and (4) to determine the PK/PD endpoints and PK/PDco values in order to predict the optimal dose regimen of cephalothin for antimicrobial prophylaxis in dogs. Anesthesia/surgery significantly reduced cephalothin clearance by 18.78%. Based on the results of this study, a cephalothin dose regimen of 25 mg/kg q6h by intravenous administration showed to be effective against Staphylococcus spp. isolates with MIC values ≤2 µg/mL and could be recommended for antimicrobial prophylaxis for clean surgery in healthy dogs.


Assuntos
Doenças do Cão , Infecções Estafilocócicas , Cães , Animais , Cefalotina/farmacologia , Cefalotina/uso terapêutico , Antibacterianos , Staphylococcus aureus , Coagulase/farmacologia , Coagulase/uso terapêutico , Infecções Estafilocócicas/prevenção & controle , Infecções Estafilocócicas/veterinária , Staphylococcus , Testes de Sensibilidade Microbiana/veterinária , Doenças do Cão/tratamento farmacológico , Doenças do Cão/prevenção & controle
18.
J Perinatol ; 44(5): 724-730, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38351274

RESUMO

OBJECTIVE: To assess the impact of active surveillance and decolonization strategies on methicillin-resistant Staphylococcus aureus (MRSA) infection rates in a NICU. STUDY DESIGN: MRSA infection rates were compared before (2014-2016) and during (2017-2022) an active surveillance program. Eligible infants were decolonized with chlorohexidine gluconate (CHG) bathing and/or topical mupirocin. Successful decolonization and rates of recolonization were assessed. RESULTS: Fifty-two (0.57%) of 9 100 hospitalized infants had invasive MRSA infections from 2014 to 2022; infection rates declined non-significantly. During the 6-year surveillance program, the risk of infection was 16.9-times [CI95 8.4, 34.1] higher in colonized infants than uncolonized infants. Those colonized with mupirocin-susceptible MRSA were more likely successfully decolonized (aOR 9.7 [CI95 4.2, 22.5]). Of 57 infants successfully decolonized who remained hospitalized, 34 (60%) became recolonized. CONCLUSIONS: MRSA infection rates did not significantly decline in association with an active surveillance and decolonization program. Alternatives to mupirocin and CHG are needed to facilitate decolonization.


Assuntos
Antibacterianos , Clorexidina , Infecção Hospitalar , Unidades de Terapia Intensiva Neonatal , Staphylococcus aureus Resistente à Meticilina , Mupirocina , Infecções Estafilocócicas , Humanos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/prevenção & controle , Infecções Estafilocócicas/tratamento farmacológico , Recém-Nascido , Mupirocina/administração & dosagem , Mupirocina/uso terapêutico , Clorexidina/análogos & derivados , Clorexidina/administração & dosagem , Clorexidina/uso terapêutico , Feminino , Masculino , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Anti-Infecciosos Locais/administração & dosagem , Anti-Infecciosos Locais/uso terapêutico , Banhos
19.
NEJM Evid ; 3(2): EVIDtt2300302, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38320491

RESUMO

Are Contact Precautions for Patients with MRSA Useful?MRSA infections lead to substantial morbidity and mortality. Hospitals commonly implement "contact precautions" to reduce MRSA transmission; however, recent studies have challenged the effectiveness of this strategy, and the use of contact precautions has been associated with certain adverse events. This article reviews the existing evidence and proposes a randomized trial to assess the efficacy of contact precautions in preventing MRSA transmission.


Assuntos
Infecção Hospitalar , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Infecção Hospitalar/prevenção & controle , Infecções Estafilocócicas/prevenção & controle , Controle de Infecções , Hospitais
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