Delafloxacin: a novel fluoroquinolone with activity against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa

Introduction: The resistance to current antimicrobial agents, including fluoroquinolones, has continued to grow among various pathogens indicating a need for new antimicrobials to combat multi-drug resistant (MDR) organisms. In June 2017, delafloxacin received approval by the US Food and Drug Administration for the treatment of acute bacterial skin and skin-structure infections (ABSSSIs) in adults caused by designated susceptible bacteria.

Areas covered: This review describes the pharmacology, pharmacodynamics, pharmacokinetics, product information, efficacy, and safety of delafloxacin.

Expert commentary: Delafloxacin is a novel oral and intravenous fluoroquinolone with activity against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, offering a new option for the treatment of ABSSSI and potentially for complicated urinary tract infections and severe community-acquired bacterial pneumonia.     

Staphylococcus aureus,master manipulator of the human hemostatic system

Summary

The coagulation system does not only offer protection against bleeding, but also aids in our defense against invading microorganisms. The hemostatic system and innate immunity are strongly entangled, which explains why so many infections are complicated by either bleeding or thrombosis. Staphylococcus aureus (S. aureus), currently the most deadly infectious agent in the developed world, causes devastating intravascular infections such as sepsis and infective endocarditis. During these infections S. aureus comes in close contact with the host hemostatic system and proves to be a master in manipulating coagulation. The coagulases of S. aureus directly induce coagulation by activating prothrombin. S. aureus also manipulates fibrinolysis by triggering plasminogen activation via staphylokinase. Furthermore, S. aureus binds and activates platelets and interacts with key coagulation proteins such as fibrin(ogen), fibronectin and von Willebrand factor. By manipulating the coagulation system S. aureus gains a significant advantage over the host defense mechanisms. Studying the interplay between S. aureus and the hemostatic system can therefore lead to new innovative therapies for battling S. aureus infections.

     

Evaluating Epidemiology and Improving Surveillance of Infections Associated with Health Care,United States

The Healthcare-Associated Infections Community Interface (HAIC), launched in 2009, is the newest major activity of the Emerging Infections Program. The HAIC activity addresses population- and laboratory-based surveillance for Clostridium difficile infections, candidemia, and multidrug-resistant gram-negative bacilli. Other activities include special projects: the multistate Healthcare-Associated Infections and Antimicrobial Use Prevalence Survey and projects that evaluate new approaches for improving surveillance. The HAIC activity has provided information about the epidemiology and adverse health outcomes of health care–associated infections and antimicrobial drug use in the United States and informs efforts to improve patient safety through prevention of these infections.     

Staphylococcus aureus bacteremia and endocarditis

The prevalence of Stapylococcus bacteriaemia is increasing worldwide, because of the increasing use of invasive procedures leading to nosocomial infections, but also of a changing way of life (increasing fashion for tattoos or piercing, use of intravenous drugs). Infective endocarditis develops in 10-30% of the cases of staphylococcus bacteriaemia. Staphylococcus aureus endocarditis must be suspected when it develops in the year following heart surgery or implantation of permanent devices. In drug users, it usually involves the tricuspid valve. According to the resistance of the germ to meticillin, antibiotic therapy uses a combination of intravenous penicillin or glycopeptide and an aminoside. Other antibiotics such as fosfomycin, rifampicin, fusidic acid, or clindamycin can be used when aminosides are contra-indicated. The role of newer antibiotic agents, such as daptomycin or linezolide, remains to be established.     

Tubuloreticular Inclusions and Paired Cisternae Induced in Human Lymphocytes Cultured with Staphylococcus Aureus Cowan 1

Tubuloreticular inclusions (TRI) and paired cisternae (PC) were induced in lymphocytes of normal individuals after incubation with Staphylococcus aureus Cowan 1. TRI were initially detected in lymphoid cells on day 2 (48-h culture). The frequency of TRI-positive cell sections on day 5 increased about twofold over those on days 2–4. On day 7, TRI were predominantly seen in lymphoplasmacytoid cells or plasmacytoid cells, with an incidence of up to 18% of sections. The regions in these cells were most extensive and anastomosed with the cisternae of adjacent well-developed rough endoplasmic reticulum (RER). TRI formation appears not to be essential for mitogen-induced B-cell differentiation to plasmacytoid cells, because poke-weed mitogen (PWM) failed to induce TRI. The diverse expressions of TRI induction between these two mitogens may be due to a difference in B-cell activation mechanisms.

Paired cisternae were observed in a great majority of mitotic cells at various stages. These were encountered most frequently on day 4. PC were also seen in the PWM-stimulated culture. Our observations suggest that PC formation may be related to new formation of RER as well as to reconstruction of the nuclear envelope.     

Surface roughness enhances upward migration of bacteria on polymer fibers above liquid cultures

Monofilament polypropylene (PP) fibers, very similar to fibers that have been used as monofilament tailstrings of interuterinc contraceptive devices, were suspended vertically in bacterial liquid monocultures so that a portion of a fiber extended above the liquid surface. In some cases these highly oriented, cold drawn fibers were abraded prior to insertion in the cultures in order to produce surface roughness characterized by axial channels and protruding microfibrils that partially peeled from the fiber surface thereby forming the channels. Extent of migration on a fiber was assessed by aseptically cutting it into small segments, followed by culturing each segment on agar containing growth medium. Such assessment of the PP fibers after 48 h of incubation in the cultures revealed upward migration of Eschericia coli, Pseudomonas aeruginosa, and Staphylococcus aureus over significantly longer distances on the pre-roughened fibers than on those not so pre-treated. Mean measured distances of migration during 48 h were: for E. coli 2.7 ± 0.6 mm on roughened fibers (n = 16) and 0.4±0.7 mm on fibers not roughened (n = 17); for S. aureus 9.0±4.3 mm on roughened fibers (n = 13) and 0.2± 0.3 mm on fibers not roughened (n = 14); for P. aeruginosa 8.5± 3.7 mm on roughened fibers (n = 26) and 0.2± 0.5 mm on fibers not roughened (n = 5). Although no statistically significant (95% confidence level) difference could be discerned between the migration distances of S. aureus and P. aeruginosa, each of these species migrated a greater distance on the PP than did E. coli. The migrations observed are attributed predominantly to wicking of the liquid cultures upward in the axial grooves developed on the surface of the PP by the eruption and peeling of microfibrils from the surface. Surface tension of the growth medium was significantly lower than that of water and its contact angle on PP was less than 90 deg, thereby indicating a tendency to wet the PP. Bacterial growth in the medium further reduced its contact angle on PP, thereby indicating an even greater tendency to wet PP after such growth.     

The effectiveness of dalethyne dressings for reducing bacteria in diabetic foot ulcers

Objective: This study evaluates the effectiveness of a dalethyne dressing for decreasing bacteria in diabetic patients with infected foot ulcers. Methods: This study was conducted from March to September 2018 with a sample of 30 par ticipants from the outpatient Kitamura Wound Clinic in Pontianak City, Indonesia. A quasi-experimental non-equivalent pretest–posttest control group design was used for the study. Participants were divided into two groups: an intervention group (treated with a dalethyne dressing) and a control group (treated with a standard dressing). Two trained research assistants collected the data using the Wagner wound classification system and a bacteria counter. The assistants swabbed each wound surface with sterile cotton, and the swabs were used to conduct a bacteria culture and count. Results: The study population was 50％ female and 50％ male with no significant differences between each other in age, HbA1c, blood pressure, or ankle-brachial index (ABI; P > 0.05). Both groups had a significant reduction in the number of bacteria from the pretest to posttest (P < 0.05). Mann–Whitney analysis of posttest data indicated a significant difference in bacteria reduction between the control group (median = 2.25) and the intervention group (median = 7.6; P = 0.018). It was noted that Staphylococcus aureus was found in the control group at posttest, but not in the intervention group. Conclusions: This study provides evidence that a dalethyne dressing is effective for killing S. aureus in the infected foot ulcers of diabetic patients.     

2016~2019年陕西省榆林市细菌耐药监测网成员单位金黄色葡萄球菌的临床分布与耐药性变迁

目的　分析 2016-2019年陕西省榆林市细菌耐药监测网成员单位金黄色葡萄球菌临床分布与耐药性变迁,为金黄色葡萄球菌感染合理用药提供依据。方法　收集 2016~2019年陕西省榆林市细菌耐药监测网成员单位（榆林市一院、榆林市二院、府谷县人民医院、神木市医院、榆林星元医院、定边县医院、靖边县医院、绥德县医院共 8家医院）常规分离、培养的 1 296株金黄色葡萄球菌的监测数据,所有检测按 CLSI2019规定的标准执行。结果　1 296株金黄色葡萄球菌（ SAU）从科室分布看,主要分布在外科（ 19.3%）、儿科（ 13.1%）、重症医学科（ 8.7%）和骨科（ 8.2%）;从标本类型分布看,主要分布在痰液（ 23.8%）、分泌物（ 22.7%）、脓液（ 13.7%）和伤口（ 11.9%）。在 1 296株 SAU中甲氧西林耐药金黄色葡萄球菌（ MRSA）占比为 20.2%;MRSA比甲氧西林敏感金黄色葡萄球菌（ MSSA）抗生素耐药率明显偏高,两组之间的差异有统计学意义（ P<0.01）;四年内对青霉素耐药率都在 93.3%以上;对红霉素耐药率都在 62.7%以上;对克林霉素耐药率都在 26.8%以上;对复方新诺明耐药率都在 25%以下,且有连续下降的趋势;对氯霉素、利福平、环丙沙星、莫西沙星和庆大霉素的耐药性都在 15%以下;对利奈唑胺、万古霉素、替考拉宁和呋喃妥因四类药物尚未产生耐药性。结论　利奈唑胺、万古霉素、替考拉宁及呋喃妥因均可作为 SAU感染的经验用药,除此外其他抗生素选用建议要参照药敏试验进行,以此来促进金黄色葡萄球菌感染的精准治疗并延缓耐药菌株的出现。