The antibacterial activity of topical retinoids: the case of retinaldehyde

BACKGROUND: Retinoids such as retinoic acid (RA), retinol (ROL) and retinaldehyde (RAL) are currently used in many formulations and indications ranging form acne to skin aging. Most if not all their pharmacological activities occur through binding to nuclear receptors with subsequent modulation of the activities of several genes. Little attention has been given to the many other potential actions on the surface of the skin. AIM: To analyse the potential anti-infective activities of topical ROL, RAL and RA. METHODS: Microbial minimal inhibitory concentrations (MIC) of ROL, RAL and RA were determined by a microdilution method on reference strains including Staphylococcus aureus, Staphylococcus epidermidis, Micrococcus flavus, Propionibacterium acnes, Micrococcus luteus, Enterococcus faecium, Staphylococcus hominis, Escherichia coli, Pseudomonas aeruginosa, Candida albicans and 133 clinical strains including methicillin-resistant S. aureus, methicillin-sensitive S. aureus, coagulase-negative Staphylococcus, Streptococcus group B, Enterococcus faecalis, vancomycin-resistant E. faecalis, vancomycin-resistant E. faecium and Pseudomonas/Klebsiella. In two clinical trials in healthy human volunteers, skin bacterial densities were evaluated in samples obtained with the cylinder scrub method: (1). 2 and 5 h after a single application of 0.05% RAL or vehicle on the forearm and (2). in a single-blind randomized study where 0.05% RAL or vehicle were applied daily for 2 weeks on the forehead of 22 volunteers. Paired results from treated (or vehicle) and untreated areas were analysed. RESULTS: Of the three retinoids tested, only RAL showed a significant in vitro antibacterial activity; this activity was found against reference strains of gram-positive bacteria like S. aeureus, Micrococcus spp. or P. acnes. No activity was found against gram-negative bacteria. These results on reference strains were confirmed on 133 clinical isolates. MIC(50) and MIC(90) values for RAL were 8 and 16 mg/l, respectively, for methicillin-sensitive S. aureus and 4 and 8 mg/l for methicillin-resistant S. aureus. The two in vivo studies showed that areas treated with RAL had a significant decrease in the bacterial counts. In the forehead study, the median decrease was 10(2) log/cm(2) for P. acnes and 10(1.8) log/cm(2) for staphylococci. No resistant bacteria were found after 2 weeks of topical use. Preliminary results suggest that the antibacterial effect of RAL is due, in part, to the aldehyde group in the lateral chain, since non-retinoid pseudo-analogues of the chain, like citral and hexenal, showed a similar antibacterial activity. CONCLUSION: We have shown that RAL differs from parent natural retinoids such as ROL and RA in demonstrating significant antibacterial activities upon topical use. This activity is likely due to the aldehyde group in the isoprenoic lateral chain, which illustrates the potential bifunctional properties of some retinoids.     

287例男性泌尿生殖道感染病原体分析

为进一步了解目前我国男性泌悄生殖道感染的病因，利用细菌培养、解脲支原体培养、免疫荧光检测沙眼衣原体等方法，对２８７例男性泌尿生殖道感染患者进行病原体检测。结果２８２例检出病原体，其中淋球菌７８例（２７．６５％），解脲支原体４９例（１７．３７％），沙眼衣原体４５例（１５．９５％），较国内其它报道少；而非特异性细菌感染物别是在慢性前列腺炎中增加，尤以金黄色葡萄球菌为甚，共９８例，占病例总数的３４．７５     

Synergistic effect of antibacterial agents human beta-defensins, cathelicidin LL-37 and lysozyme against Staphylococcus aureus and Escherichia coli

BACKGROUND: The antimicrobial properties of the skin are attributed to several agents including human beta-defensins (hBDs), cathelicidin LL-37 and skin lysozyme. Although these antibacterial agents reside in the skin to protect it against infection, it is not well known whether the total analysis of all combinations of these agents may result in synergistic effect to enhance their antibacterial activities against invading microorganisms. OBJECTIVE: To elucidate the interactions between keratinocyte-derived antibacterial agents in the extracellular milieu, we investigated the individual and synergistic activities of hBDs, LL-37 and lysozyme against Staphylococcus aureus and Escherichia coli in neutral and acidic milieus. METHODS: The colorimetric method using alamarBlue was employed to assess the antibacterial activities of hBD-1, -2, -3, LL-37 and lysozyme and the viability of bacteria was read spectrophotometrically. RESULTS: In both neutral and acidic pH milieus, hBD-1, -2, -3, LL-37 and lysozyme exhibited antibacterial activity against S. aureus and E. coli in a dose-dependent manner. Interestingly, the antibacterial activity of hBD-1, -2, -3 and lysozyme but not LL-37 was significantly enhanced in acidic milieu (pH 4.6). Furthermore, various combinations of above agents resulted in a synergistic or additive antibacterial effect against S. aureus and E. coli in neutral milieu. The synergistic effect of hBDs, LL-37 and lysozyme against S. aureus was further significantly enhanced in acidic milieu. In contrast, above antibacterial agents exhibited mainly additive rather than synergistic effect on antibacterial activity against E. coli in acidic milieu. CONCLUSION: Taken together, these results provide a novel evidence of antimicrobial mechanism of natural human skin-derived antibacterial agents against bacterial infection, and their involvement in innate immunity.     

Palmitoleic acid isomer (C16:1delta6) in human skin sebum is effective against gram-positive bacteria

The percent lipid composition of pooled human sebum analyzed by thin-layer chromatography was: ceramides (13%), fatty acid (47%), cholesterol (7%), cholesterol esters (2%), squalene (11%), triglycerides (3%), and wax esters (17%). Total sebum lipids (2- 4 mg/ml), sonicated into bacterial culture medium, caused 4- to 5-fold log reduction in growth of gram-positive bacteria, Staphylococcus aureus, Streptococcus salivarius and the anaerobe Fusobacterium nucleatum, but was ineffective against most gram-negative bacteria. Fractionation of the sebum lipids showed that both saturated and unsaturated fatty acids contained the bulk of the antimicrobial activity. Lauric acid (C12:0) was the most active saturated fatty acid. The unsaturated fatty acid, palmitoleic acid (C16:1delta6, cPA) was both the most predominant monoene and the most active antimicrobial fatty acid. Purified cPA (>99%) yielded typical minimal inhibitory concentration (MIC) values of 10-20 microg/ml against gram-positive bacteria. Organically synthesized cPA isomer gave MIC values comparable to the natural material. Both natural and synthetic cPA were found to be the most active sebum lipid fraction in blocking the adherence of a pathogenic strain of Candida albicans to porcine stratum corneum. Ethanol in combination with cPA exerts a synergistic bactericidal activity against gram-negative pathogenic bacteria, including Pseudomonas aeruginosa, Propionibacterium acnes, Escherichia coli, and several methacillin-resistant strains of S. aureus. Palmitoleic acid may be useful in topical formulations for treatment of secondary gram-positive bacterial infections, as a gram-positive bacteria antimicrobial in wound dressings, and as a natural gram-positive antimicrobial preservative in skin and hair care products.     

Decreased levels of sphingosine,a natural antimicrobial agent,may be associated with vulnerability of the stratum corneum from patients with atopic dermatitis to colonization by Staphylococcus aureus

The stratum corneum of the skin of patients with atopic dermatitis is highly susceptible to colonization by various bacteria, including Staphylococcus aureus. The defense system of the skin against bacterial invasion appears to be significantly disrupted in atopic dermatitis skin, but little is known about the defense mechanism(s) involved. As one sphingolipid metabolite, sphingosine is known to exert a potent antimicrobial effect on S. aureus at physiologic levels, and it may play a significant role in bacterial defense mechanisms of healthy normal skin. Because of the altered ceramide metabolism in atopic dermatitis, the possible alteration of sphingosine metabolism might be associated with the acquired vulnerability to colonization by S. aureus in patients with atopic dermatitis. In this study, we measured the levels of sphingosine in the upper stratum corneum from patients with atopic dermatitis, and then compared that with the colonization levels of bacteria in the same subjects. Levels of sphingosine were significantly downregulated in uninvolved and in involved stratum corneum of patients with atopic dermatitis compared with healthy controls. This decreased level of sphingosine was relevant to the increased numbers of bacteria including S. aureus present in the upper stratum corneum from the same subjects. This suggests the possibility that the increased colonization of bacteria found in patients with atopic dermatitis may result from a deficiency of sphingosine as a natural antimicrobial agent. As for the mechanism involved in the decreased production of sphingosine in atopic dermatitis, analysis of the activities of ceramidases, major sphingosine-producing enzymes, revealed that, whereas the activity of alkaline ceramidase did not differ between patients with atopic dermatitis and healthy controls, the activity of acid ceramidase was significantly reduced in patients with atopic dermatitis and this had obvious relevance to the increased colonization of bacteria in those subjects. Further, there was a close correlation between the level of sphingosines and acid ceramidase (r = 0.65, p < 0.01) or ceramides (r = 0.70, p < 0.01) in the upper stratum corneum from the same patients with atopic dermatitis. Collectively, our results suggest the possibility that vulnerability to bacterial colonization in the skin of patients with atopic dermatitis is associated with reduced levels of a natural antimicrobial agent, sphingosine, which results from decreased levels of ceramides as a substrate and from diminished activities of its metabolic enzyme, acid ceramidase.     

Antimicrobial peptides: potential use in skin infections

Antimicrobial peptides are part of the natural defense against infections in all phyla, including humans. Antimicrobial peptides are considered to be promising alternatives to conventional antimicrobials. Antimicrobial peptides are active against a wide spectrum of pathogens, including multidrug-resistant bacteria, fungi, viruses and parasites. Thus, they are promising candidates for treatment of various skin infections, also infections caused by bacteria such as methicillin resistant Staphylococcus aureus and vancomycin resistant enterococci. However, there are some obstacles, e.g. low tissue penetrability, high production costs, and unknown cytotoxicity, to overcome before antimicrobial peptides will be readily available for the treatment of infectious diseases. Topical administration may solve some of these problems. Some antimicrobial peptides are currently in clinical trials, including peptides developed for treatment of skin infections.     

MICROBIOLOGY OF SECONDARILY INFECTED DIAPER DERMATITIS

Specimens obtained from 67 infants with secondarily infected diaper dermatitis were cultured for aerobic and anaerobic bacteria. Bacteria growth was obtained in 58. Aerobic facultative bacteria or Candida sp. only were present in 28 patients (48%), anaerobic bacteria only in 11 (19%), and mixed anaerobic with aerobic, facultative, or yeast flora was present in 19 (33%). Ninety-one bacterial or fungal isolates were recovered (1.6 per specimen), 54 (0.9 per specimen) aerobic or facultative bacteria, 8 (0.1 per specimen) Candida sp., and 31 (0.6 per specimen) strict anaerobes. The predominant aerobic and facultative bacteria were Staphylococcus aureus (23 isolates), Streptococcus sp. (16), and Escherichia coli (6). The predominant anaerobes included Bacteroides sp. (12, including 9 Bacteroides fragilis group) and Peptostreptococcus sp. (11). Single bacterial isolates were recovered in 32 (55%) patients, 18 of which were S. aureus. Twenty-five beta-lactamase-producing bacteria were detected in 22 (51%) of the 43 tested patients. These included 16 S. aureus and 6 B. fragilis group. These data highlight the importance of anaerobic bacteria in the polymicrobial nature of secondarily infected diaper dermatitis.     

Coagulase-negative staphylococci are the most common bacteria found in cultures from the deep portions of hidradenitis suppurativa lesions, as obtained by carbon dioxide laser surgery

The significance of bacterial findings in hidradenitis suppurativa (HS) is controversial. Interpretation of the results of bacteriological examinations from the surface of HS lesions is obscured by the possible contamination of resident skin bacteria. Bacteriological analysis of aspirates from deeper parts of HS is liable to show low sensitivity. We used a carbon dioxide (CO2) laser method to evaporate the diseased tissue level by level from the surface downwards, allowing concurrent sampling of bacteriological cultures from each level and thereby minimizing contamination with bacteria from the level above. In this study, 22 women and three men with a mean age of 35.3 years and a mean HS duration of 10.6 years were treated with this CO2 laser surgical method. Aerobic and anaerobic cultures from superficial and deep levels were taken during surgery. The regions treated were axillary in eight and perineal in 17 cases. Bacterial cultures were positive for one or more specimens from at least one level in all cases and from deep levels in all but three cases. Sixteen different species or sub-species were found. Staphylococcus aureus and coagulase-negative staphylococci (CNS) were the species most frequently found. Peptostreptococcus species and Propionibacterium acnes were not uncommon. S. aureus was detected in a total of 14 cases, six of which were from the deep levels. S. aureus was the sole bacterium isolated in two deep cultures. CNS were found in 21 patients and 16 of these isolates were from the deep levels. In nine of the 16 deep samples CNS were the only bacteria detected. These findings motivate a re-evaluation of the significance of bacteria in the progress of HS and in particular they suggest that CNS are true pathogens. It is known that foreign bodies aggravate the virulence of the CNS in surgical implants, and an environment which resembles that produced by a foreign body, as found in chronic HS tissue, serves to intensify the pathogenic properties of CNS in HS.     

Bactericidal activity of manganese and iodide ions against Staphylococcus aureus: a possible treatment for acute atopic dermatitis.

We reported previously that balneotherapy using Kusatsu hot-spring water is useful for controlling the skin symptoms of acute flares/exacerbations of refractory cases of atopic dermatitis. As Staphylococcus aureus on the skin surface decreased in number or disappeared after balneotherapy, the hot-spring water was suspected to act against the microorganism. The hot-spring water showed strong bactericidal activity against S. aureus in vitro. In order to clarify the mechanism further, the bactericidal activity of the hot-spring water was examined by adding back cations and anions in same concentrations as those in the original hot-spring water, one at a time to cation- and anion-exchanged hot-spring water. The findings clearly demonstrated that the bactericidal activity was expressed by manganese and iodide ions in acidic conditions (pH 2.0-3.0). Thus, the probable mechanism for the improvement of skin manifestations through Kusatsu balneotherapy is the bactericidal activity of the hot-spring water against S. aureus. When added to water acidified with sulphuric acid (pH 2.0-3.0) a synergistic effect of the 2 ions was observed, so that an anti-staphylococcal effect was obtained even at low concentrations (1 mg/kg). Acidic solutions containing manganese and iodide ions may thus be clinically useful for treating skin conditions caused by S. aureus.     

Community-acquired methicillin resistant Staphylococcus aureus skin infection

Staphylococcus aureus is one of the most common pathogens in skin and soft tissue infections, as well as in potentially serious nosocomial infections in patients who acquire it when hospitalized. Penicillin was introduced in the 1940's as an effective treatment against S. aureus. However, shortly after penicillin's introduction, penicillin resistance to S. aureus emerged due to a plasmid-mediated beta-lactamase enzyme. In 1959, a semisynthetic penicillin, methicillin was introduced to overcome the resistance problem. However, within a year, bacteria resistant to methicillin and other penicillinase stable beta-lactams, were present. Worldwide emergence of methicillin-resistant S aureus (MRSA) was established by the 1980's. Since that time, MRSA has become widespread in hospitals and long-term care facilities around the world, accounting for numerous nosocomial infections. Recently, there has been an alarming increase in the incidence of community-acquired MRSA (CA-MRSA). Patients with CA-MRSA began to be reported in the early 1990's and its prevalence has continued to increase. This paper summarizes the current information known about CA-MRSA as it relates to skin infections including populations at risk, clinical presentation, and treatment options.     

Noninvasive in vivo imaging to evaluate immune responses and antimicrobial therapy against Staphylococcus aureus and USA300 MRSA skin infections

Staphylococcus aureus skin infections represent a significant public health threat because of the emergence of antibiotic-resistant strains such as methicillin-resistant S. aureus (MRSA). As greater understanding of protective immune responses and more effective antimicrobial therapies are needed, a S. aureus skin wound infection model was developed in which full-thickness scalpel cuts on the backs of mice were infected with a bioluminescent S. aureus (methicillin sensitive) or USA300 community-acquired MRSA strain and in vivo imaging was used to noninvasively monitor the bacterial burden. In addition, the infection-induced inflammatory response was quantified using in vivo fluorescence imaging of LysEGFP mice. Using this model, we found that both IL-1α and IL-1β contributed to host defense during a wound infection, whereas IL-1β was more critical during an intradermal S. aureus infection. Furthermore, treatment of a USA300 MRSA skin infection with retapamulin ointment resulted in up to 85-fold reduction in bacterial burden and a 53% decrease in infection-induced inflammation. In contrast, mupirocin ointment had minimal clinical activity against this USA300 strain, resulting in only a 2-fold reduction in bacterial burden. Taken together, this S. aureus wound infection model provides a valuable preclinical screening method to investigate cutaneous immune responses and the efficacy of topical antimicrobial therapies.     

Assessment of cadexomer iodine against Staphylococcus aureus biofilm in vivo and in vitro using confocal laser scanning microscopy

Cadexomer iodine releases iodine (0.9% weight/weight) slowly from beads of dextrin and epichlorhydrin. This preparation is an effective debridement and antiseptic agent for chronic exdudative wounds. The purpose of the present study is to examine the influence of cadexomer iodine against glycocalyx production of Staphylococcus aureus isolated from furuncle lesions on cut wounds in mice using confocal laser scanning microscope (CLSM), and the increase in and glycocalyx production of S. aureus in vitro. In the present study, distinct S. aureus cells and glycocalyx were not detected in the dermis around the cadexomer iodine beads or within those beads, while S. aureus cells encircled by glycocalyx were soaked up by the cadexomer beads and were detected within them in vivo and in vitro. We suggest that cadexomer iodine soaks up S. aureus cells encircled by glycocalyx, directly destroys biofilm structures, and collapses glycocalyx during dehydration, and further, that iodine can subsequently kill S. aureus cells within biofilm. Cadexomer iodine is a promising treatment to clear S. aureus cells within biofilm from skin lesions of exudative or infectious wounds and to prevent wound exacerbation.     

The role of bacteria on facial rosacea-like dermatitis in adult type atopic dermatitis

To investigate the role of bacteria on facial rosacea-like dermatitis lesion in adult type atopic dermatitis, we measured the numbers of bacteria on the skin, nasal and pharyngeal surface of each individual, and then examined its sensitivity to antibiotics. The numbers of bacteria on the surface of skin increased according to the severity of skin eruption. Staphylococcus aureus was detected from the skin and nasal surface more than pharyngeal surface. Bacteria on the pharyngeal surface were both staphylococcus aureus and haemophilus parainfluenzae. Therefore, it is suggested that bacterial flora on the pharynx is different from those of the skin and nose. The treatment with antibiotics was effective for exudative lesions, whereas lichenified lesion did not respond to antibiotic therapy. These results suggest that bacteria on the skin surface are one of precipitating factors of the rosacea-like dermatitis of atopic dermatitis.     

天然抗角蛋白IgM调理巨噬细胞吞噬金黄色葡萄球菌的作用

目的 探讨天然抗角蛋白IgM对金黄色葡萄球菌的结合反应和介导调理吞噬的功能。方法 ELISA法及间接免疫荧光法检测天然抗角蛋白IgM抗体3B4与金黄色葡萄球菌的结合。将3B4与金黄色葡萄球菌作用后与巨噬细胞共孵育,菌落形成实验及流式细胞仪分析3B4介导细菌的调理吞噬作用。结果 ELISA与间接免疫荧光均发现3B4可以与细菌结合,菌落形成实验显示3B4作用组菌落数量显著少于阴性对照组,流式细胞仪分析显示巨噬细胞对3B4作用后细菌的吞噬作用明显增强。结论 天然抗角蛋白IgM抗体3B4可以结合并介导调理吞噬金黄色葡萄球菌,提示天然IgM在抗细菌天然免疫中具有一定的作用。     

Antimicrobial effects of acidic hot-spring water on Staphylococcus aureus strains isolated from atopic dermatitis patients

The present study examined the antimicrobial effects of acidic hot-spring water on Staphylococcus aureus strains isolated from atopic dermatitis (AD) patients. Plasma coagulation by S. aureus cells was not detected in plasma containing acidic hot-spring water (60%, pH 5.4) or hydrochloric acid (pH 5.0) after incubation for 24 h. S. aureus cells did not grow in Mueller-Hinton broth with acidic hot-spring water (50%, pH 4.4) after 24 h incubation. The colony counts of S. aureus cells in tryptic soy broth containing acidic hot-spring water (60%, pH 3.9) were over ten times lower than those in tryptic soy broth alone after incubation for 24 h (P<0.01). A membranous structure (an immature biofilm) was formed on the coverslips of tissue culture dishes by S. aureus cells in plasma after incubation for 24 h, although the colony counts of S. aureus cells in the immature biofilms in plasma containing acidic hot-spring water (60%, pH 5.4) were about eight times lower than those in plasma alone after incubation for 24 h (P<0.01). The colony counts of S. aureus cells that attached on coverslips in plasma containing acidic hot-spring water (60%, pH 5.4) or hydrochloric acid (pH 5.4) were over 1000 times lower than those in plasma alone after incubation for 24 h. These results suggest that 50% acidic hot-spring water has a bacteriostatic effect, 60% acidic hot-spring water has a moderate bactericidal effect against floating S. aureus cells and those cells in a biofilm, and, 60% acidic hot-spring water has an inhibitory effect on plasma coagulation and attachment of S. aureus cells. Furthermore, our present results suggest that a small amount of some ions in hot-spring water such as manganese and iodide ions are very important for a bactericidal activity of hot-spring water as well as the low pH condition.     

Antibiotic treatment of hidradenitis suppurativa

Bacterial infection plays an important role in hidradenitis suppurativa (HS). This infection has a number of unique features: chronicity, absence of lymph node involvement, and absence in most cases of acute super-infection by Staphylococcus aureus and/or streptococci. Treatment is based mainly on antibiotics. Various bacteria are involved; they are often part of the resident flora and may combine in polymicrobial infections, and they consist mainly of two families: coagulase-negative staphylococci (CNS) and anaerobes. Numerous antibiotics are active against CNS: betalactamins, lincosamides, macrolides, rifampicin, tetracyclines and fluoroquinolones. Antibiotics active against anaerobes include metronidazole, betalactamins, lincosamides and one fluoroquinolone (moxifloxacine). Antibiotics are given per os and in combination. Treatment is usually long-term, with a frequent need for maintenance therapy. It has to be tailored to various clinical situations: intermittent development, in which "abortive" emergency treatment is used; major or major continuous forms, where combined antibiotics are used, most frequently rifampicin and clindamycin. The global treatment strategy involves a surgical approach, which can be aided but not replaced by antibiotics. While the risks of long-term antibiotic use are reduced in this specific population of "healthy" young adults, they are not absent.     

天然抗角蛋白自身抗体抗小鼠金黄色葡萄球菌感染的研究

目的 以高滴度天然抗角蛋白自身抗体(AK auto Ab)转基因小鼠为模型,分析AK auto Ab在抵御金黄色葡萄球菌感染中的作用.方法 取天然抗角蛋白自身抗体转基因小鼠及阴性对照小鼠,ELISA法检测小鼠腹腔冲洗液总IgM、抗角蛋白IgM抗体以及抗金黄色葡萄球菌IgM抗体水平:腹腔接种金黄色葡萄球菌制备感染模型,检测腹腔接种金黄色葡萄球菌后腹腔及肾脏菌落形成单位数量.测定菌负荷,流式细胞仪检测中性粒细胞比率、炎症因子浓度等.结果 ELISA检测发现,转基因小鼠腹腔冲洗液抗角蛋白IgM、抗金黄色葡萄球菌IgM水平高于阴性对照小鼠.差异有统计学意义(P<0.01);菌落形成实验显示,转基因小鼠腹腔及肾脏菌负荷低于阴性对照(P<0.01):流式细胞仪分析发现.转基因小鼠腹腔中性粒细胞比率、炎症因子浓度低于阴性对照(P<0.01).结论 AK auto Ab在小鼠体内对金黄色葡萄球菌感染具有良好的保护作用.     

非特应性的湿疹皮炎患者皮肤菌群的测定与分析

目的：探讨非特应性的湿疹皮炎患者携带细菌尤其是金黄色葡萄球菌（金葡菌）的携带情况。方法：选取正常人30名及门诊非特应性的湿疹皮炎患者186例，以棉签法分别在正常人及皮损部位反复擦拭后进行细菌培养及鉴定。结果：正常人未检出金葡菌；湿疹继发感染患者皮损金葡菌及细菌总检出率均为92.9%；非特应性的湿疹皮炎患者金葡菌检出率和细菌总检出率分别为30.1%和67.7%；临床无感染的湿疹皮炎患者金葡菌检出率和细菌总检出率分别为25.0%和65.7%，后两者金葡菌及细菌总检出率均显著低于湿疹继发感染患者，而金葡菌检出率显著高于正常人。结论：金葡菌与一部分非特应性的湿疹皮炎可能有一定的关系。     

The Role of Fluoroquinolones in Skin and Skin Structure Infections

Skin and skin structure infections encompass a broad range of clinical presentations and disease severity. Antimicrobial therapy is clearly beneficial for both recovery from these infections as well as preventing disease progression. Fluoroquinolones are potent broad spectrum antimicrobial agents with the older agents characterized as having broad spectrum anti-Gram-negative activity, borderline activity against clinically important Gram-positive pathogens and little or no anti-anaerobic bacteria activity. In contrast, the new quinolones are characterized by having enhanced activity against Gram-positive pathogens, anti-anaerobic activity and they remain highly active against aerobic-Gram-negative bacilli. Several fluoroquinolones have been evaluated for the treatment of uncomplicated skin and soft tissue infection, difficult skin and soft tissue infection and serious skin and skin structure infections. Clinical cure rates were found to be equivalent to comparators suggesting a role for the fluoroquinolone in treating these infections. It may be necessary to use some fluoroquinolones in combination with anti-anaerobic agents for those infections with mixed aerobic and anaerobic pathogens. Some additional clinical trials are necessary to identify the full potential of newer fluoroquinolones for skin and skin structure infections. At present, quinolones are, in general, equivalent to beta-lactam agents in the treatment of skin and soft tissue infection.     

Cutaneous infections in the elderly: diagnosis and management

Over the past several years there have been many advances in the diagnosis and treatment of cutaneous infectious diseases. This review focuses on the three major topics of interest in the geriatric population: herpes zoster and postherpetic neuralgia (PHN), onychomycosis, and recent advances in antibacterial therapy. Herpes zoster in adults is caused by reactivation of the varicella-zoster virus (VZV) that causes chickenpox in children. For many years acyclovir was the gold standard of antiviral therapy for the treatment of patients with herpes zoster. Famciclovir and valacyclovir, newer antivirals for herpes zoster, offer less frequent dosing. PHN refers to pain lasting > or = 2 months after an acute attack of herpes zoster. The pain may be constant or intermittent and may occur spontaneously or be caused by seemingly innocuous stimuli such as a light touch. Treatment of established PHN through pharmacologic and nonpharmacologic therapy will be discussed. In addition, therapeutic strategies to prevent PHN will be reviewed. These include the use of oral corticosteroids, nerve blocks, and treatment with standard antiviral therapy. Onychomycosis, or tinea unguium, is caused by dermatophytes in the majority of cases, but can also be caused by Candida and nondermatophyte molds. Onychomycosis is found more frequently in the elderly and in more males than females. There are four types of onychomycosis: distal subungual onychomycosis, proximal subungual onychomycosis, white superficial onychomycosis, and candidal onychomycosis. Over the past several years, new treatments for this disorder have emerged which offer shorter courses of therapy and greater efficacy than previous therapies. The treatment of bacterial skin and skin structure infections in the elderly is an important issue. There has been an alarming increase in the incidence of gram-positive infections, including resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and drug-resistant pneumococci. While vancomycin has been considered the drug of last defense against gram-positive multidrug-resistant bacteria, the late 1980s saw an increase in vancomycin-resistant bacteria, including vancomycin-resistant enterococci (VRE). More recently, strains of vancomycin-intermediate resistant S. aureus (VISA) have been isolated. Gram-positive bacteria, such as S. aureus and Streptococcus pyogenes are often the cause of skin and skin structure infections, ranging from mild pyodermas to complicated infections including postsurgical wound infections, severe carbunculosis, and erysipelas. With limited treatment options, it has become critical to identify antibiotics with novel mechanisms of activity. Several new drugs have emerged as possible therapeutic alternatives, including linezolid and quinupristin/dalfopristin.