Dequalinium chloride use in adult Spanish women with bacterial vaginosis: an observational study.

Bacterial vaginosis (BV) represents the most frequent vaginal infection in women of childbearing age. The aim of this study was to characterise episodes of BV among adult Spanish women and their management with dequalinium chloride (DQC). Data from 573 DQC-treated BV adult women was obtained on medical records and questionnaires. The study shows that 20.6% had presented vaginal infections previously. Comorbid candidosis was significantly associated to other symptoms, such as pruritus or leucorrhoea. Most patients (64.3%) indicated a moderate-strong impact of the BV episode on their sexual life. After treatment, 84.8% of patients reported no BV symptoms. Patients were given instructions to prevent relapses. Most patients (83.1%) rated DQC as 'satisfactory' or 'very/extremely satisfactory' regarding symptom relief, prevention or treatment of the episode of BV. In conclusion, this study provides a better understanding of BV episodes and the impact of the treatment with DQC in real clinical practice in Spanish patients.IMPACT STATEMENTWhat is already known on this subject? Bacterial vaginosis (BV) is the most commonly reported vaginal infection among women of childbearing age. Despite the availability of antibiotic medications for the treatment of BV, management of this condition remains challenging. In fact, recurrence of BV has been reported for up to 50% of cases. However, antiseptic agents are considered an effective option for BV treatment.What the results of this study add? The study provides a better understanding of the prevalent symptomatology and the impact on quality of life of women with BV. Moreover, it has been observed that antiseptic dequalinium chloride (DQC) efficiently reduces symptoms and improves quality of life of the patients during episodes of BV.What the implications are of these findings for clinical practice and/or further research? In the context of the World Health Organisation recommendations on the rational use of antibiotics, we believe that the use of DQC may be a good alternative to antibiotics as a therapy for BV.

Rupatadine oral solution in children with persistent allergic rhinitis: A randomized, double-blind, placebo-controlled study.

BACKGROUND: Allergic rhinitis (AR) is one of the most common chronic diseases in childhood. No large, multicentre clinical trials in children with persistent allergic rhinitis (PER) have previously been performed. Rupatadine, a newer second-generation antihistamine, effective and safe in adults, is a promising treatment for children with AR. The aim of the present study was to evaluate the efficacy and safety of a new rupatadine oral solution in children aged 6-11 yr with PER. METHODS: A multicenter, randomized, double-blind, placebo-controlled study was carried out worldwide. Patients between 6 and 11 yr with a diagnosis of PER according to ARIA criteria were randomized to receive either rupatadine oral solution (1 mg/ml) or placebo over 6 wk. The primary efficacy end-point was the change from baseline of the total nasal symptoms score (T4SS) after 4 wk of treatment. RESULTS: A total of 360 patients were randomized to rupatadine (n = 180) or placebo (n = 180) treatment. Rupatadine showed statistically significant differences vs. placebo for the T4SS reduction both at 4 (-2.5 ± 1.9 vs. -3.1 ± 2.1; p = 0.018) and 6 wk (-2.7 ± 1.9 vs. -3.3 ± 2.1; p = 0.048). Rupatadine also showed a statistically better improvement in the children's quality of life compared with placebo. Adverse reactions were rare and non-serious in both treatment groups. No QTc or laboratory test abnormalities were reported. CONCLUSIONS: Rupatadine oral solution (1 mg/ml) was significantly more effective than placebo in reducing nasal symptoms at 4 and 6 wk and was well tolerated overall. This is the first large clinical report on the efficacy of an H1 receptor antagonist in children with PER in both symptoms and quality of life.

Epidemiology of uterine myomas and clinical practice in Spain: An observational study.

OBJECTIVE: Characterization of the clinical features of symptomatic uterine myomas in Spanish women visiting the gynaecologist, including impact on quality of life and possible risk factors, description of main therapeutic approaches, and evaluation of symptom and quality of life progression 6 months after inclusion in the study. STUDY DESIGN: This was an observational, epidemiological, non-interventional, multicentre study performed between June 2015 and March 2016. Data were collected at baseline and follow-up visits 6 months apart from women with a diagnosis of uterine myomas and visiting a participating gynaecologist in outpatient units of private clinics or public hospitals in Spain. Data consisted of a gynaecological clinical inspection, an interview with open questions to the patients, and self-administered generic questionnaires. The main outcome measures were socio-demographic data, clinical history, myoma clinical features, symptomatology, data on surgical choices, patient satisfaction, and risk factors associated to myomas. RESULTS: Data were collected from 569 patients (1,022 myomas) at 56 hospitals and private gynaecological offices in Spain. Most patients (85%) presented between 1 and 3 myomas, predominantly intramural and subserosal. Most common symptoms reported heavy menstrual bleeding and pelvic pain, and the mean (±SD) symptom severity score in the UFS-QoL questionnaire (range 0-100) was 50.89 ±â€¯20.85. Up to 60.5% of patients had an indication of surgery (55.8% myomectomies, 40.4% hysterectomies) to treat their uterine myomas and 39.5% followed other therapies, mainly pharmacological. After six months of treatment, all patients had experienced significant reduction in symptoms and improvement of quality of life. CONCLUSIONS: The most frequent symptoms reported by women diagnosed with uterine myomas were heavy menstrual bleeding, pelvic or abdominal pain and dysmenorrhea; QoL was impaired reflecting high symptom distress. We found that surgery was the main therapeutic approach to manage uterine myomas in Spain. Both surgical and non-surgical treatments achieve relevant improvements in symptom severity and quality of life.

Evaluation of antimicrobial regimens in a guinea-pig model of meningitis caused by Pseudomonas aeruginosa.

To compare the efficacy of meropenem, ceftazidime, tobramycin and ceftazidime+tobramycin in a guinea-pig model of P. aeruginosa meningitis. After anesthesia, the atlanto-occipital membrane was punctured with a butterfly needle and 100 microl of a solution containing 10(6)CFU/ml of P. aeruginosa were injected directly into the cisterna magna. Four h later, therapy was initiated with saline or antibiotics given im for 48 h in doses that obtained CSF levels as in human meningitis: ceftazidime 200 mg/kg/8h, meropenem 200 mg/kg/8h, tobramycin 30 mg/kg/24h. Tobramycin was also given intracisternally. Animals were sacrificed at different time points. CSF and blood samples were collected and a meningeal swab was performed. Four hours after inoculation, bacterial concentration in CSF was 4 to 5log10CFU and mean WBC was 16,000/-l. All control animals died in 24h with a 12% increase in cerebral edema. All blood-cultures were negative. Ceftazidime, ceftazidime+tobramycin and meropenem reduced the CSF bacterial concentration at 8h by 2.5log10. At 48 h all CSF cultures were sterile but meningeal swab cultures remained positive in 30%. Our results suggest that meropenem may be at least as effective as ceftazidime and that the addition of tobramycin to ceftazidime may improve its efficacy.

A mouse peritonitis model for the study of glycopeptide efficacy in GISA infections.

In recent years, the emergence of Staphylococcus aureus strains with reduced susceptibility to glycopeptides has raised considerable concern. We studied the efficacy of vancomycin and teicoplanin, as well as cloxacillin and cefotaxime, against the infection caused by four S. aureus strains with different glycopeptide and beta-lactam susceptibilities (strains A, B, C, and D; MICs for vancomycin of 1, 2, 4, and 8 microg/ml respectively), using a modified model of mouse peritonitis. This optimized model appeared to be straightforward and reproducible, and was able to detect low differences in bacterial killing between antibiotics and also between different S. aureus strains. Bactericidal activities in peritoneal fluid for vancomycin, teicoplanin, cloxacillin, and cefotaxime decreased from -2.98, -2.36, -3.22, and -3.57 log(10) cfu/ml, respectively, in infection by strain A (MICs for vancomycin and cloxacillin of 1 and 0.38 microg/ml, respectively) to -1.22, -0.65, -1.04, and +0.24 in peritonitis due to strain D (MICs for vancomycin and cloxacillin of 8 and 1,024 microg/ml). Our data confirm the superiority of beta-lactams against methicillin-susceptible S. aureus and show that bactericidal activity of glycopeptides decreases significantly with slight increases in MICs; this finding suggests a reduced efficacy of glycopeptides in the treatment of serious glycopeptide-intermediate S. aureus infections.

Evaluation of nasal symptoms induced by platelet activating factor, after nasal challenge in both healthy and allergic rhinitis subjects pretreated with rupatadine, levocetirizine or placebo in a cross-over study design.

BACKGROUND: Platelet-activating factor (PAF) is produced by most inflammatory cells and it is involved in inflammatory and allergic reactions. We aimed to assess the anti-PAF effects of rupatadine and levocetirizine in the upper airways. FINDINGS: Healthy volunteers (HV, N = 10) and seasonal allergic rhinitis (SAR, N = 10) asymptomatic patients were treated out of the pollen season with either rupatadine 20 mg, levocetirizine 10 mg, or placebo once a day during 5 days prior to the PAF nasal challenge. Total 4-nasal symptom score (T4SS) and nasal patency (Vol2-5, by acoustic rhinometry) were assessed from 0 to 240 minutes after a repeated PAF challenge. In SAR patients but not in HV, both rupatadine and levocetirizine showed a trend to decrease PAF-induced T4SS from 60 to 120 minutes. Rupatadine but not levocetirizine caused a significant reduction (p < 0.05) of T4SS area under the curve compared to placebo. Rupatadine and levocetirizine caused no significant changes on nasal patency compared to placebo. CONCLUSIONS: These results suggest that both rupatadine and levocetirizine showed a tendency decrease toward nasal symptoms, but only rupatadine significally reduces the overall nasal symptoms (AUC) induced by PAF in SAR patients.

Efficacy of linezolid alone and in combination with rifampin in staphylococcal experimental foreign-body infection.

OBJECTIVES: The knowledge about efficacy of linezolid alone or in combination with rifampin in device infections is limited. We test their in vitro and in vivo efficacy in a rat model of foreign-body infection by methicillin-susceptible S. aureus. METHODS: In vitro studies for logarithmic and stationary bacteria were performed. In vivo efficacy (decrease in bacterial counts in tissue cage fluid) was evaluated at: (i) after 7-day therapy (groups: linezolid, cloxacillin, rifampin, linezolid-rifampin and cloxacillin-rifampin); and (ii) after 10-day therapy (groups: rifampin and linezolid-rifampin). RESULTS: After 7-day therapy all groups were significantly better than controls; linezolid (Delta log cfu/ml: -0.59, no resistant strains) and cloxacillin (-0.85) were the least effective therapy; linezolid was significantly less active (P<0.05) than rifampin (-1.22, resistance 90%), cloxacillin-rifampin (-1.3) and linezolid-rifampin (-1.14). After 10-day therapy linezolid-rifampin was the most effective treatment (Delta log -1.44, no resistance, P<0.05); in contrast, rifampin resulted ineffective (Delta log 0.1) due to the growth of resistant strains (100%). CONCLUSIONS: Linezolid alone showed moderate efficacy, whereas its combination with rifampin prevented the emergence of rifampin resistance. The efficacy of linezolid-rifampin combination was initially similar to that of rifampin alone, but in contrast to rifampin, it increased over time revealing the impact of protection against rifampin resistance and the benefits of rifampin activity.

Evaluation of fosfomycin alone and in combination with ceftriaxone or vancomycin in an experimental model of meningitis caused by two strains of cephalosporin-resistant Streptococcus pneumoniae.

OBJECTIVES: To study the in vitro and in vivo efficacy of fosfomycin, alone and in combination with ceftriaxone or vancomycin, against two strains of Streptococcus pneumoniae: HUB 2349 (fosfomycin and ceftriaxone, MICs 16 and 2 mg/L) and ATCC 51916 (MICs 4 and 32 mg/L). METHODS: Pharmacokinetics/pharmacodynamics data were collected from the study of eight infected animals after a single intravenous dose of 300 mg/kg of fosfomycin. Time-kill curves were plotted using CSF antibiotic concentrations achievable clinically. In the rabbit model, we studied the efficacy and effects on inflammation of treatment with fosfomycin 1200 mg/kg/day, ceftriaxone 100 mg/kg/day and vancomycin 30 mg/kg/day, over 26 h. RESULTS: Fosfomycin peak level in serum was 324.48 +/- 102.1 mg/L at 0.5 h; CSF penetration was 49.2%. Time-kill curves showed that fosfomycin was bactericidal against the ATCC 51916 strain and that the addition of fosfomycin to ceftriaxone or vancomycin was synergic against the HUB 2349 strain. Resistance to fosfomycin was detected both when fosfomycin was studied alone and in combination. In the rabbit model, fosfomycin showed bactericidal activity only against the ATCC 51916 strain. Combinations of fosfomycin with ceftriaxone or vancomycin were bactericidal against both strains; they improved efficacy and decreased CSF inflammatory parameters over monotherapies, without showing statistical differences in comparison with the combination of ceftriaxone and vancomycin. CONCLUSIONS: Fosfomycin in combination with ceftriaxone or vancomycin appeared to be effective for the treatment of experimental cephalosporin-resistant pneumococcal meningitis. These combinations are possible alternatives in cases of allergy or intolerance to first-line drugs or in rare meningitis caused by highly cephalosporin-resistant pneumococci.

Evaluation of ceftriaxone, vancomycin and rifampicin alone and combined in an experimental model of meningitis caused by highly cephalosporin-resistant Streptococcus pneumoniae ATCC 51916.

OBJECTIVES: The aim of the study was to assess the in vitro and in vivo efficacy of ceftriaxone, vancomycin and rifampicin alone and combined against Streptococcus pneumoniae ATCC 51916 (MIC of ceftriaxone: 32 mg/L). METHODS: In vitro killing curves were performed with clinically achievable CSF antibiotic concentrations. In the rabbit model of pneumococcal meningitis, we studied the efficacy of and effects on inflammation of treatment with ceftriaxone 100 mg/kg/day, vancomycin 30 mg/kg/day and rifampicin 15 mg/kg/day, alone and combined, over a 26 h period. RESULTS: Time-kill curves showed that vancomycin was bactericidal, and ceftriaxone and rifampicin produced a bacteriostatic effect. An additive effect was observed when combinations of ceftriaxone plus vancomycin were studied at subinhibitory concentrations. Emergence of resistance to rifampicin was detected both when rifampicin was studied alone and when combined with ceftriaxone or vancomycin. In the rabbit meningitis model, ceftriaxone was bacteriostatic, whereas rifampicin and vancomycin were bactericidal at 24 h. Although not synergistic, the combinations of ceftriaxone plus vancomycin or rifampicin, and vancomycin plus rifampicin, improved the efficacy of any antibiotic tested alone--all combinations were bactericidal from 6 h--and significantly decreased inflammatory parameters in CSF compared with control and ceftriaxone groups. CONCLUSION: Ceftriaxone plus vancomycin, and vancomycin plus rifampicin appeared to be effective in the therapy of experimental pneumococcal meningitis caused by highly cephalosporin-resistant strains such as ATCC 51916. Our results provide an experimental basis for using these combinations as empirical therapy for pneumococcal meningitis, regardless of the degree of cephalosporin resistance of the causative strain.

Experimental study on the efficacy of combinations of glycopeptides and beta-lactams against Staphylococcus aureus with reduced susceptibility to glycopeptides.

OBJECTIVES: The combination of glycopeptides and beta-lactams has been proposed as an alternative therapy against infections due to Staphylococcus aureus with reduced susceptibility to glycopeptides, though its role is still controversial. Our aim was to evaluate the efficacy (decrease in bacterial concentration after 24 h therapy) of these combinations both in vitro and in vivo. METHODS: Four strains of S. aureus with different glycopeptide susceptibility (MICs of vancomycin from 1 to 8 mg/L) were used. In vitro experiments were performed by means of time-kill curves while we used the mouse peritonitis model for in vivo evaluation. RESULTS: Combinations of glycopeptides and beta-lactams showed synergy in in vitro time-kill curves against the four staphylococcal strains, the highest efficacy being detected against the glycopeptide-intermediate S. aureus (GISA) strain (MIC = 8 mg/L) (Deltalog 24 h = -3.19 cfu/mL for vancomycin at 1/2 x MIC and oxacillinat 1/64 x MIC versus -0.56 cfu/mL for vancomycin alone at 1/2 x MIC). On the other hand, no significant increase in efficacy was observed in vivo in the experimental model. The efficacy of the combinations decreased in correlation to the decreasing susceptibility of the strains to glycopeptides, showing only residual activity against the GISA strain (Deltalog 24 h = -1.42 cfu/mL for vancomycin and cloxacillin versus -1.22 cfu/mL for vancomycin). CONCLUSIONS: In the in vivo setting we were unable to demonstrate the synergism between glycopeptides and beta-lactams observed in vitro; nor did combinations show antagonism against any of the strains. Though the usefulness of these combinations cannot be totally ruled out in highly specific clinical conditions, it seems unlikely that they will provide a serious therapeutic alternative in most hGISA and GISA infections in the coming years.

Antibiotic combinations for serious infections caused by carbapenem-resistant Acinetobacter baumannii in a mouse pneumonia model.

OBJECTIVES: Successful therapy of carbapenem-resistant Acinetobacter baumannii strains has been reported with colistin, but recently we argued against its use as monotherapy because of the poor results obtained in a mouse pneumonia model. Our aim was to identify antibiotic combinations that were valid therapeutic alternatives in the same model. METHODS: We used two carbapenem-resistant A. baumannii strains (D and E; MICs of imipenem, 8 and 512 mg/L, respectively). MICs of tobramycin, rifampicin and colistin for both strains were 8, 8 and 0.5 mg/L, respectively. RESULTS: In infections caused by strain D, lung bacterial counts (log(10) cfu/g, mean +/- s.d.) were: controls (10.86+/-0.25), imipenem (5.99+/-0.59, P < 0.05 versus controls), and colistin (10.43 +/- 1.09); imipenem + tobramycin was the most active combination (5.46+/-0.62, P < 0.05 versus controls). In infections caused by strain E, results were: controls (10.82+/-0.33), rifampicin (5.62+/-0.26, P < 0.05 versus controls), colistin (8.38+/-1.22, P < 0.05 versus controls), and imipenem (11.01+/-0.2); rifampicin + imipenem (3.79+/-0.99) and rifampicin + tobramycin (3.96+/-0.30) were the most active combinations (P < 0.05); results with rifampicin + colistin (5.59+/-1.17) were similar to those with rifampicin alone. CONCLUSIONS: Our data indicate that imipenem can still be the best alternative for carbapenem-resistant A. baumannii infections with moderate levels of imipenem resistance, preferably combined with aminoglycosides. For strains highly resistant to imipenem, a combination of rifampicin with imipenem, tobramycin or colistin may be useful, if resistance to rifampicin is only moderate.

[Experimental meningitis due to a high-level cephalosporin-resistant strain of Streptococcus pneumoniae serotype 23F]. / Meningitis experimental producida por una cepa de Streptococcus pneumoniae serotipo 23F con elevada resistencia a cefalosporinas.

INTRODUCTION: The increasing prevalence of high-level cephalosporin-resistant strains of Streptococcus pneumoniae could complicate the treatment of severe infections such as meningitis. There are still questions as to the characteristics of these strains, their ability to produce severe infection, and the inflammatory response they induce in CSF. METHODS: Using a rabbit model of meningitis, we sought to determine the pathogenicity and differences in inflammatory parameters in two serotype 23F S. pneumoniae strains with different susceptibility to betalactams. Minimal inhibitory concentrations of the two strains were as follows: strain A--PEN 4 micro g/mL, CRO/CTX 2 micro g/mL--and strain B--PEN 0.12 micro g/mL, CRO/CTX 32 micro g/mL. RESULTS: Strain A resulted in a greater incidence of secondary bacteremia and higher inflammatory parameters during the early phases of infection. Strain B caused brain edema, a more severe inflammatory response and significantly higher mortality at the end of the experiment. CONCLUSIONS: Both strains induced meningitis in the animal model. The differences in inflammatory response produced by the two strains could be related to the variations that determine the betalactam resistance level.