Methyl aminolevulinate photodynamic therapy for onychomycosis: a multicentre, randomized, controlled clinical trial.

BACKGROUND: Onychomycosis is a common fungal nail infection that responds poorly to antifungals. OBJECTIVE: To investigate the efficacy and safety of methyl aminolevulinate (MAL) photodynamic therapy (PDT) in the treatment of onychomycosis. METHODS: A multicentre (3), randomized, placebo-controlled clinical trial compared the effects of three sessions of urea (40%) plus conventional MAL-PDT with urea (40%) plus placebo (red light) photodynamic therapy (pPDT) in onychomycosis patients. Efficacy, both clinical (onychomycosis severity index, OSI) and microbiological, was blindly evaluated after 36 weeks of follow-up. RESULTS: Forty patients were analysed in the trial. Twenty-two received MAL-PDT and 18 pPDT. A complete response (OSI = 0) was observed for four patients (18.18%) in the MAL-PDT group and one (5.56%) in the pPDT group (NTT 7.92, 95% CI: 2.98-9.69, P = 0.23). A decrease in OSI score of over 75% (OSI75) was achieved by 40.91% of the patients in the MAL-PDT group and 16.67% in the pPDT group (P = 0.096). Microbiological cure was achieved by seven patients (31.82%) in the MAL-PDT group and two (11.11%) in the pPDT group (P = 0.178). MAL-PDT resulted in better rates of clinical response [OSI >75%: 53.85% vs. 18.75% (P =0.048)] and microbiological cure [41.56% vs. 7.14% (P = 0.037)] in non-dystrophic vs. dystrophic onychomycosis patients. No significant side-effects were reported. The limitations of the study were the reduced sample size and the unexpected efficacy of the control treatment, which was attributed to the 40% urea pre-treatment. CONCLUSION: This study did not show significant differences between urea 40% + MAL-PDT and urea 40% + pPDT in the treatment of onychomycosis. However, some results suggest that this treatment may constitute an alternative for dermatophyte and non-dermatophyte mould onychomycosis in patients not eligible for systemic treatment, particularly in the absence of total nail dystrophy.

Photodynamic Therapy With Methylene Blue for Skin Ulcers Infected With Pseudomonas aeruginosa and Fusarium spp. / Terapia fotodinámica con azul de metileno en úlceras cutáneas infectadas con Pseudomonas aeruginosa y Fusarium spp.

Photodynamic therapy (PDT) is a therapeutic modality with significant antimicrobial activity. We present 2 cases of chronic lower limb ulcers in which fungal and bacterial superinfection complicated management. PDT with methylene blue as the photosensitizer led to clinical and microbiological cure with no significant adverse effects. PDT with methylene blue is a valid option for the management of superinfected chronic ulcers, reducing the use of antibiotics and the induction of resistance.

Usefulness of Photodynamic Therapy in the Management of Onychomycosis.

Onychomycosis, or fungal infection of the nails, is one of the most prevalent fungal diseases in the general population. Treatment is of limited effectiveness, tedious, and must be administered for long periods. Furthermore, systemic antifungal agents are associated with adverse effects. Photodynamic therapy (PDT) may prove to be a viable alternative in the treatment of superficial skin infections, including onychomycosis. We review articles relating to the usefulness of PDT in onychomycosis in both in vitro and in vivo settings and discuss the potential and limitations of various photosensitizing agents. In vivo, methylene blue and 5-aminolevulinic acid have led to cure rates in 80% and 43% of cases, respectively, at 12 months. Finally, based on data in the literature and our own experience, we propose a protocol of 3 PDT sessions, separated by an interval of 1 or 2 weeks, using methyl aminolevulinate 16% as a photosensitizing agent and red light (λ=630 nm, 37 J.cm(-2)). Each session is preceded by the topical application of urea 40% over several days. Clinical trials are needed to optimize PDT protocols and to identify those patients who will benefit most from this treatment.

Photodynamic fungicidal efficacy of hypericin and dimethyl methylene blue against azole-resistant Candida albicans strains.

Antimicrobial photodynamic therapy (aPDT) is an emerging alternative to treat infections based on the use of photosensitisers (PSs) and visible light. To investigate the fungicidal effect of PDT against azole-resistant Candida albicans strains using two PSs with a different mechanism of action, hypericin (HYP) and 1,9-dimethyl methylene blue (DMMB), comparing their efficacy and the reactive oxygen species (ROS) species involved in their cytotoxicity. Azole-resistant and the azole-susceptible C. albicans strains were used. Solutions of 0.5 and 4 McFarland inoculum of each Candida strain were treated with different concentrations of each PS, and exposed to two light-emitting diode light fluences (18 and 37 J cm⁻²). Mechanistic insight was gained using several ROS quenchers. The minimal fungicidal concentration of HYP for ≥3 log10 CFU reduction (0.5 McFarland) was 0.62 µmol l⁻¹ for most strains, whereas for DMMB it ranged between 1.25 and 2.5 µmol l⁻¹. Increasing the fluence to 37 J cm⁻² allowed to reduce the DMMB concentration. Higher concentrations of both PSs were required to reach a 6 log10 reduction (4 McFarland). H2O2 was the main phototoxic species involved in the fungicidal effect of HYP-aPDT whereas ¹O2 was more important for DMMB-based treatments. aPDT with either HYP or DMMB is effective in killing of C. albicans strains independent of their azole resistance pattern. HYP was more efficient at low fungal concentration and DMMB at higher concentrations.

Meningitis caused by an unusual genotype (ST3) of Streptococcus suis.

We describe a case of meningitis due to Streptococcus suis with the unusual ST3 genotype. The bacterial pathogen was isolated from blood samples. S. suis genotype ST3 was initially isolated from carrier pigs, but it has not been previously associated with invasive human infections. The patient developed serious endogenous bilateral endophthalmitis which resulted in severe visual deficiency.

Detection and characterization of a ST6 clone of vanB2-Enterococcus faecalis from three different hospitals in Spain.

Thirteen vancomycin-resistant and teicoplanin-susceptible Enterococcus faecalis isolates were recovered from unrelated patients in three Spanish hospitals from November 2009 to December 2010. All isolates carried the vanB2 gene, showed indistinguishable or closely-related PFGE patterns and were ascribed to the sequence type ST6 (included into the high-risk clonal-complex CC2). They showed a multiresistance phenotype (erythromycin, tetracycline, ciprofloxacin and high-level-resistance to streptomycin, gentamicin and kanamycin) and harboured the aac(6')-aph(2"), ant(6)-Ia, and tet(M)+/-tet(L) genes. All isolates produced gelatinase and harboured the gelE gene, but not the esp or hyl genes. The inclusion of the vanB2 gene into the Tn5382 transposon was demonstrated in one isolate. Clonal dissemination of vanB2-containing the E. faecalis strain is demonstrated.

Differential characteristics of bacteraemias according to age in a community hospital. / Características diferenciales en las bacteriemias según la edad en un hospital comunitario.

OBJECTIVE: To describe the characteristics of bacteraemias, according to age, in a community hospital. MATERIAL AND METHOD: A prospective study of bacteraemias was conducted in 2011. The patients were classified into 3 age groups: younger than 65 years, 65 to 79, and 80 or older. The study collected variables on the patients and episodes. RESULTS: The study analysed 233 bacteraemias in 227 patients (23.8% in those younger than 65 years; 38.3% in the 65 to 79 age group; and 37.9% in the 80 years or older group). The most common underlying disease in all the groups was diabetes mellitus. In the most elderly patients, the Charlson index was highest, there was a lower proportion of exogenous factors, and almost 25% were severely dependent (Barthel index<20). Escherichia coli was the most common germ, and the main focus was urological. The patients aged 80 years or older had predominantly healthcare-associated infections, less severe symptoms (sepsis) (66.3%) and higher mortality (29.1%) compared with the younger patients. CONCLUSIONS: The very elderly patients with bacteraemia presented fewer exogenous factors, greater comorbidity and a poorer functional situation. The most common focus was urological and the origin was healthcare related. Despite their less severe clinical presentation, these patients' mortality was greater, and their degree of dependence was a highly relevant independent risk factor.

In vitro activity of cefepime and cefotaxime compared to six other agents against 350 penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae.

From January 1996 to December 1997, we evaluated the in vitro activity of 8 antimicrobials (penicillin, amoxycillin, amoxycillin/clavulanate, cefuroxime, ceftazidime, cefepime, cefotaxime, and imipenem) against 350 Streptococcus pneumoniae clinical isolates collected from two hospitals. Imipenem, cefepime and cefotaxime were the most active antibiotics against penicillin-intermediate (PI) and highly penicillin-resistant (PR) S. pneumoniae with MICs 2- to 8-fold lower than penicillin. Against PI and PR pneumococci amoxycillin and amoxycillin/clavulanate were 2-times less active than cefepime and cefotaxime, while cefuroxime was 4-8-times less active. The majority of strains of serotypes 6B, 23F, 14, 9 and 19 were penicillin-resistant, both intermediate (68%) and highly resistant (32%).

[Tuberculous splenic abscess in an immunocompetent patient]. / Absceso esplénico tuberculoso en paciente inmunocompetente.

Splenic tuberculosis is a rare entity. The case of an 18-year old patient admitted for fever and general malice is described. Echography and abdominal CT showed a hypodense image localized in the spleen. Splenic tuberculosis was diagnosed upon observation of alcohol acid resistant bacilli (AARB) in the biopsy obtained by punction of the abscess. Correct tuberculostatic treatment led to disappearance of the splenic abscess with no further therapeutic measures being required.

Methicillin-resistant Staphylococcus aureus (MRSA) ST398 in a farmer with skin lesions and in pigs of his farm: clonal relationship and detection of lnu(A) gene.

Skin infection associated with methicillin-resistant Staphylococcus aureus (MRSA)-ST398 was detected in a pig-farmer, and MRSA-ST398 isolates were also detected in nasal samples of the patient and of 11/12 pigs on his farm. Twelve MRSA isolates were obtained from skin lesions (n = 6) and nasal samples (n = 6) of the patient in two sampling moments and 11 MRSA isolates from nasal samples of pigs. They were typed as t011-SCCmecIVa-agrI and t108-SCCmecV-agrI (patient and pigs) and t588-SCCmecV-agrI (patient). The following resistance genes were detected (number isolates): tet(K) (1), tet(L) (23), tet(M) (13), erm(A) (13), erm(C) (13), msr(A) (11), lnu(A) (21), aph(2'')-acc(6') (3), ant(4') (13), aph(3') (12), dfrS1 (15) and dfrK (22). Seventeen human and animal MRSA-ST398 isolates showed indistinguishable PFGE patterns (A1-spa-t011 or B2-spa-t108) and similar phenotypic-genotypic characteristics, including the presence of the lnu(A) gene, associated with lincomycin resistance. Potential pig-to-human transference of ST398 is suggested in this study. The first detection of the lnu(A) gene in MRSA-ST398 is reported.

Differentiation of three biotypes of Malassezia species on human normal skin. correspondence with M. globosa, M. sympodialis and M. restricta.

One hundred and twenty lipid dependent Malassezia spp. isolates were obtained from the clinically normal skin of 38 healthy adult volunteers by swabbing three different body sites (back, chest and scalp). Ninety-six percent of these strains could be grouped into three biotypes on the basis of microscopic, cultural, metabolic and biochemical (catalase, esculin and lipase (C-14)) characteristics. The differential features were simple to determine and easily reproduced. Moreover, the three biotypes were referable to the species M. globosa (biotype 1), M. sympodialis (biotype 2) and M. restricta (biotype 3). Based on their microscopic features, cultural properties and body site locations, we suggest that biotype 1 /M. globosa corresponds to the description of Pityrosporum orbiculare (round yeast cells with a narrow base, very frequently found on the upper trunk), and biotype 3/M. restricta corresponds to the concept of P. ovale (oval yeast cells with a broad budding base, located mainly on the scalp). Pleomorphic biotype 2/M. sympodialis, most frequently found in the back, does not clearly fit into any of the Pityrosporum species.

[Resistance to penicillin and other antimicrobials in 301 clinical isolates of Streptococcus pneumoniae]. / Resistencia a penicilina y otros antimicrobianos en 301 aislamientos clínicos de Streptococcus pneumoniae.

BACKGROUND: The aim of this study was to assess the susceptibility to penicillin of Streptococcus pneumoniae clinical strains and to analyze the association between penicillin resistance and cefotaxime and cefixime activity in S. pneumoniae isolates with decreased sensitivity to penicillin. METHODS: 301 S. pneumoniae clinical strains were isolated from patients during 1995-1996. Susceptibility to penicillin, cefotaxime, cefepime, erythromycin, chloramphenicol, tetracycline, cotrimoxazole and ciprofloxacin were studied. RESULTS: 38.2% isolates were penicillin-susceptible and 61.8% were penicillin-resistant; 20.6% showed high-level resistance. Resistance rates to erythromycin, chloramphenicol, tetracycline, cotrimoxazole and ciprofloxacin were, respectively, 30.9, 30.2, 40.9, 66.4, and 13.3% overall, and 54.8, 54.8, 61.3, and 93.5% in the 62 strains with high-level resistance to penicillin. Strains resistant to cefotaxime and cefepime were 13.9 and 14.9%, respectively. MIC50 and MIC90 for cefotaxime and cefepime in penicillin-resistant strains were 0.5 and 1 mg/ml. CONCLUSIONS: A high proportion of S. pneumoniae isolates showed resistance to penicillin, in agreement with other Spanish reports. Moreover, resistance to penicillin was significantly associated (p < 0.001) with resistance to erythromycin, chloramphenicol, tetracycline and cotrimoxazole, but not with ciprofloxacin. MIC50 and MIC90 for cefotaxime and cefepime were similar, and lower than those for penicillin in penicillin-resistant pneumococci strains.