Factors associated with development of nephrotoxicity in patients treated with vancomycin versus daptomycin for severe Gram-positive infections: A practice-based study.

OBJECTIVE: To evaluate nephrotoxicity development in patients treated with vancomycin (VAN) and daptomycin (DAP) for proven severe Gram-positive infections in daily practice. METHODS: A practice-based, observational, retrospective study (eight Spanish hospitals) was performed including patients ≥18 years with a baseline glomerular filtration rate (GFR)>30 mL/min and/or serum creatinine level<2 mg/dL treated with DAP or VAN for >48h. Nephrotoxicity was considered as a decrease in baseline GRF to <50 mL/min or decrease of >10 mL/min from a baseline GRF<50 mL/min. Multivariate analyses were performed to determine factors associated with 1) treatment selection, 2) nephrotoxicity development, and 3) nephrotoxicity development within each antibiotic group. RESULTS: A total of 133 patients (62 treated with DAP, 71 with VAN) were included. Twenty-one (15.8%) developed nephrotoxicity: 4/62 (6.3%) patients with DAP and 17/71 (23.3%) with VAN (p=0.006). No differences in concomitant administration of aminoglycosides or other potential nephrotoxic drugs were found between groups. Factors associated with DAP treatment were diabetes mellitus with organ lesion (OR=7.81, 95%CI:1.39-4.35) and basal creatinine ≥0.9 mg/dL (OR=2.53, 95%CI:1.15-4.35). Factors associated with VAN treatment were stroke (OR=7.22, 95%CI:1.50-34.67), acute myocardial infarction (OR=6.59, 95%CI:1.51-28.69) and primary bacteremia (OR=5.18, 95%CI:1.03-25.99). Factors associated with nephrotoxicity (R2=0.142; p=0.001) were creatinine clearance<80 mL/min (OR=9.22, 95%CI:1.98-30.93) and VAN treatment (OR=6.07, 95%CI:1.86-19.93). Factors associated with nephrotoxicity within patients treated with VAN (R2=0.232; p=0.018) were congestive heart failure (OR=4.35, 95%CI:1.23-15.37), endocarditis (OR=7.63, 95%CI:1.02-57.31) and basal creatinine clearance<80 mL/min (OR=7.73, 95%CI:1.20-49.71). CONCLUSIONS: Nephrotoxicity with VAN was significantly higher than with DAP despite poorer basal renal status in the DAP group.

[A comparative study of aggression towards Primary Care and Hospital Health professionals in a Madrid health area (2009-2014)]. / Estudio comparativo de las agresiones a sanitarios entre Atención Primaria y Atención Especializada en una zona de Madrid (2009-2014).

INTRODUCTION: The aim of this paper is perform an analysis on the incidents and attacks against medical personnel that occurred in the area covered by the Prevention Service Group, comparing the results in Primary Care (PC) with Hospital Care (HC). MATERIAL AND METHODS: The information available in the database of the regional Madrid Register of Aggressions Conflict Health Worker between 2009 and 2014 was analysed. This included a total of 8,056 workers, of whom 1,605 were from PC. RESULTS: A total of 1,262 incidents have been reported, of which 61.2% took place in HC and 38.8% in PC (32.2 notifications/100,000 inhabitants, or 12.88 incidents/100 hospital workers compared to 168.98 notifications/100,000 inhabitants, or 30.53 incidents/100 PC workers). Nurses in CP have a higher incidence of assaults (47.4%), while in HC it is the physicians (53.1%) (P<.001). In PC the aggressor is usually the patient (56.9%), while in HC it is the relative or companion (45.3%) (P<.001). HC aggressions occur more frequently in emergency departments (35.5%) compared with 63.9% in PC, where they occur in the consulting room (P<.001). CONCLUSIONS: Although it is difficult to make comparisons with previous studies due to methodological differences, a higher incidence of aggression in PC is observed compared with HC. It is necessary to establish improvements in Madrid Register of Aggressions and Conflicts, designed to optimise data quality and use them for preventive purposes.

Diagnostic and prognostic significance of flow cytometry immunophenotyping in patients with leptomeningeal carcinomatosis.

Some patients with epithelial-cell cancers develop leptomeningeal carcinomatosis (LC), a severe complication difficult to diagnose and with an adverse prognosis. This study explores the contribution of flow cytometry immunophenotyping (FCI) to the diagnosis and prognosis of LC. Cerebrospinal fluid (CSF) samples from patients diagnosed with LC were studied using FCI. Expression of the epithelial-cell adhesion molecule (EpCAM) was the criterion used to identify the epithelial cells. To test the diagnostic precision, 144 patients (94 diagnosed with LC) were included. The prognostic value of FCI was evaluated in 72 patients diagnosed with LC and eligible for therapy. Compared with cytology, FCI showed greater sensitivity and negative predictive value (79.79 vs. 50%; 68.85 vs. 51.55%, respectively), but lower specificity and positive predictive value (84 vs. 100%; 90.36 vs. 100%, respectively). The multivariate analysis revealed that the percentage of CSF EpCAM+ cells predicted an increased risk of death (HR: 1.012, 95% CI 1.000-1.023; p=0.041). A cut-off value of 8% EpCAM+ cells in the CSF distinguished two groups of patients with statistically significant differences in overall survival (OS) (p=0.018). This cut-off value kept its statistical significance regardless of the absolute CSF cell-count. The FCI study of the CSF improved the sensitivity for diagnosing LC, but refinement of the technique is needed to improve specificity. Furthermore, quantification of CSF EpCAM+ cells was revealed to be an independent prognostic factor for OS in patients with LC eligible for therapy. An 8% cut-off value contributed to predicting clinical evolution before initiation of therapy.

Breakthrough symptoms during the daytime in patients with restless legs syndrome (Willis-Ekbom disease).

BACKGROUND: It is often assumed that most patients with restless legs syndrome (RLS) only experience symptoms at night. However, previous studies have estimated the prevalence of daytime symptoms to be 10-60%. This study sought to investigate the prevalence and pattern of daytime symptoms in patients with moderate-to-severe RLS. METHODS: Observational, cross-sectional investigation. A self-administered questionnaire was sent out, on a random basis, to 310 patients with RLS by the Spanish RLS patient support group. Only individuals with a confirmed diagnosis of RLS were included in the final survey. RESULTS: In total, 224 individuals were included in the survey (response rate 72%). Over 55% of patients reported daytime crises on most (>3) days of the week, and 41% suffered daytime symptoms on a daily basis. These breakthrough crises were characterized by unexpected and sudden symptoms and were frequently precipitated by a reduction in daytime activity. The mean severity of these crises on a visual analogue scale (range 0-10) was 6.8 (standard deviation 2.1), and they had a major impact on quality of life. The prevalence of breakthrough crises was related to duration of illness but not to duration of treatment. CONCLUSION: This study suggests that breakthrough crises are common in moderate-to-severe RLS and have a negative effect on quality of life. More studies are needed to investigate whether breakthrough crises reflect disease progression or, at least for those patients undergoing dopaminergic treatment, whether they represent an early indication of RLS augmentation.

Serotype distribution and susceptibility of Streptococcus pneumoniae isolates from pleural fluid in Spain from 1997 to 2008.

Trends in serotype incidence and susceptibility (1997 to 2008) of Spanish Streptococcus pneumoniae pleural isolates (n = 831) were explored. Penicillin (oral) nonsusceptibility rates and the incidence of 7-valent pneumococcal conjugate vaccine (PCV-7) serotypes showed decreasing trends (R(2) ≥ 0.600; P ≤ 0.002). The incidence of serotypes 1 and 19A showed increasing trends (R(2) ≥ 0.759; P < 0.001), with no trends for serotype 3. Serotypes 19A, 1, and 3 represented 85% of pediatric isolates in 2008. In serotype 19A, the penicillin nonsusceptibility rate was 82.4% in 2008, associated with amoxicillin and cefotaxime nonsusceptibility in 21.4% of isolates. Inclusion of these serotypes in new vaccines offers the broadest coverage.

In vitro interference of beta-lactams with biofilm development by prevalent community respiratory tract isolates.

Interference of cefditoren (CDN) and amoxicillin/clavulanic acid (AMC) with biofilm production was studied using 11 Streptococcus pneumoniae isolates with minimum inhibitory concentrations (MICs) ranging from 0.015microg/mL to 0.5microg/mL for CDN and from 0.06microg/mL to 2microg/mL for AMC (except for one isolate with an AMC MIC of 8microg/mL) and 5 Haemophilus influenzae isolates with MICs of 0.03-0.06microg/mL for CDN and 0.5-16microg/mL for AMC. Slime production was assessed in antibiotic-free medium and with 0.03microg/mL CDN or 1/0.5microg/mL AMC by measuring the optical density at 450nm (OD(450)). Significantly lower mean OD(450) values were obtained for S. pneumoniae with antibiotics compared with controls (CDN, 0.088 vs. 0.118, P=0.003; and AMC, 0.095 vs. 0.112, P=0.003), with significant correlation between both antibiotics (r=0.752; P=0.008). Percent reduction in OD(450) values was higher for CDN compared with AMC (24.02% vs. 15.92%; P=0.008). For H. influenzae, significantly lower mean OD(450) values were obtained with CDN compared with controls (0.083 vs. 0.096; P=0.043) but not with AMC (0.086 vs. 0.095; P=0.08). Comparing percent reductions in S. pneumoniae versus H. influenzae for each antibiotic, no differences were found for AMC (15.92% vs. 9.40%; P=0.36), with a tendency for CDN (24.02% vs. 13.79%; P=0.069). Different beta-lactams may have different capabilities of interfering with S. pneumoniae biofilm development when tested under the same experimental conditions.

Clinical response to ertapenem in severe community-acquired pneumonia: a retrospective series in an elderly population.

To evaluate in routine hospital practice the clinical response to ertapenem in comparison with other parenteral antibiotics in the treatment of community-acquired pneumonia (CAP), clinical records from patients with severe CAP treated with ertapenem from July 2002 to June 2006 in seven Spanish hospitals were retrospectively reviewed. Patients were classified according to the Pneumonia Severity Index (PSI). Each ertapenem-treated patient was matched with two patients in the same hospital treated with other antibiotics, according to age (difference 76 years). Comorbidities were present in 193 patients (95.5%). No differences were found in median hospital stay (7 days for ertapenem vs. 10 days for comparators, p 0.066). A slightly higher clinical response rate was obtained for ertapenem vs. comparators (88.7% vs. 77.1%; p 0.0465; OR 2.25; 95% CI 0.99-5.12), with significant differences in clinical response in patients coming from nursing homes (95.8% ertapenem vs. 63.8% comparators; p 0.0034) but not in non-institutionalized patients (85.4% ertapenem vs. 84.5% comparators; p 0.929). The higher clinical response to ertapenem vs. comparators in severe CAP was due to its significantly higher efficacy in healthcare-associated CAP in patients coming from nursing homes.

Safety profile of cefditoren. A pooled analysis of data from clinical trials in community-acquired respiratory tract infections.

INTRODUCTION: A high number of individuals in the population are exposed to antibiotics for the treatment of respiratory tract infections. It is important to review the adverse events profile related to antibiotic exposure during the clinical development of drugs that are or have been recently included in the therapeutic armamentarium. MATERIAL AND METHODS: Safety data from all 13 clinical trials of cefditoren on community acquired respiratory infections were reviewed. Safety population was defined as all randomized patients with at least one dose intake. Adverse events considered by investigators as related during antibiotic exposure were considered. RESULTS: The overall safety population consisted in 4,592 patients for cefditoren and 2,784 for comparators. Overall reported diarrhoea related to cefditoren administration was significantly higher (p < or = 0.001) than comparators (9.9% vs 6.9%) due to the significant difference in the pooled pharyngotonsillitis studies (8.3% vs 3.2%), while no significant differences in others pathologies were found, with 9.4% (with cefditoren) vs 10.3% (with comparators) in the case of community-acquired pneumonia (CAP). Dyspepsia and abdominal pain were reported as adverse events in < 2.7% patients regardless the treated disease. In females population lower related vaginosis rate was found in cefditoren vs comparators, mainly due to differences among patients treated for sinusitis (4.5% vs 8.1%) and CAP (2.3% vs 5.5%) although differences were not significant (p = 0.017 and p = 0.008, respectively). CONCLUSION: This study analysing reported adverse events from clinical trials showed an adverse events profile of cefditoren similar to those of standard antibiotics used in the treatment of respiratory tract infections.

[Tinidazole: a classical anaerobical drug with multiple potential uses nowadays]. / Tinidazol: un anaerobicida clásico con múltiples usos potenciales en la actualidad.

Tinidazole is a 5-nitroimidazole active in vitro against a wide variety of anaerobic bacteria and protozoa. Tinidazole is an effective treatment against anaerobic microorganisms based on its pharmacokinetic characteristics (C(max) 51 microg/ml, t(1/2) 12.5 h) and its excellent in vitro activity. Its long half-life allows once a day regimens. Tinidazole is as effective as metronidazole in the treatment of infections caused by T. vaginalis, giardiasis and amebiasis and bacterial vaginosis, malaria, odontogenic infections, anaerobic bacterial infections (pelvic inflammatory disease, diabetic foot), surgical prophylaxis (abdominal and hysterectomy) and Helicobacter pylori eradication. Tinidazole was recently approved by the Food and Drug Administration (FDA) for the treatment of infections caused by Trichomonas vaginalis, Entamoeba histolytica and Giardia lamblia.

Temporal trends of invasive Streptococcus pneumoniae serotypes and antimicrobial resistance patterns in Spain from 1979 to 2007.

Temporal trends of serotypes from invasive pneumococcal disease (IPD) in Spain from 1979 to September 2007 under antibiotic and vaccine pressure were analyzed. A significant trend in pneumococcal conjugate 7-valent vaccine (PCV7) serotypes (except serotype 4) was found, whereby the prevalence increased from the early 1980s and decreased in the 2000s for all but serotype 23F, which began decreasing in the late 1980s. Among the major non-PCV7 serotypes, a significant decrease was observed for serotypes 1, 5, and 7F in the 1980s. From the late 1990s, serotypes 1, 5, 6A, 7F, and 19A increased significantly, while serotypes 3 and 8 showed similar but nonsignificant trends over time. The incidence of IPD cases was 10.7/100,000 for the period 1996 to 2006, with reporting coverage ranging from 18% to 43%. A significant decrease in IPD incidence due to PCV7 serotypes was observed, while the incidence of non-PCV7 serotypes increased, with the consequence that there was no clear pattern in the overall incidence of IPD. Penicillin nonsusceptibility was correlated with the proportion of PCV7 serotypes. Erythromycin nonsusceptibility increased in association with long-half-life macrolide consumption and then decreased in 2004 to 2007. The increase in PCV7 serotypes and antibiotic nonsusceptibility related to antibiotic consumption in the 1980s and 1990s was reversed in the 2000s, probably as a result of PCV7 immunization. The decrease in IPD incidence due to PCV7 serotypes was mirrored by an increase in that of non-PCV7 serotypes. The impact of various preventive/therapeutic strategies on pneumococcal evolution is serotype dependent, and the dynamics remain unpredictable.

Antimicrobial efficacy in vivo of a new formulation of 2-butanone peroxide in n-propanol: comparison with commercial products in a cross-over trial.

The use of hand rub to obtain maximum decrease in bacterial load is important because the reduction needed to avoid transmission is unknown. The monomer of 2-butanone peroxide is a peroxygen derivative with potential biocidal use in hospitals. The aim of this study was to compare the efficacy of hand rub with an alcoholic solution of peroxide 2-butanone versus five antiseptic products, against E. coli K12 (CECT 433) transient flora acquired by hand immersion in a broth culture following the UNE-EN-1500 standard. Isopropanol 60% (control) obtained 99.99% reductions, driving down the bacterial load from 10(6) cfu/mL in the initial inocula to <100 cfu/mL. Products A, B and C (different alcoholic solutions ranging from 65% to 75% with low amounts of biguanidines and/or quaternary ammonium compounds) resulted in significantly lower amounts, reducing initial inocula to approximately 500 cfu/mL. Products D and E (70-75% alcohol solutions containing higher amounts of different quaternary ammonium compounds and triclosan in the case of product E) produced reductions similar to that of isopropanol, with significantly larger reductions than products A, B and C. The product with the solution of 2-butanone peroxide produced the same effect as products D and E with mean reductions of approximately 4log(10) (99.99%), driving the initial inocula down to < or = 100 cfu/mL, despite the low concentration (35%) of propanol in the solution. This novel peroxygen biocide offers high in-vivo cidal activity against acquired E. coli transient flora, offering an alternative to products with higher alcohol concentrations.

Tinidazole inhibitory and cidal activity against anaerobic periodontal pathogens.

The in vitro activity of tinidazole against anaerobic periodontal pathogens (25 Prevotella buccae, 18 Prevotella denticola, 10 Prevotella intermedia, 6 Prevotella melaninogenica, 5 Prevotella oralis, 10 Fusobacterium nucleatum and 8 Veillonella spp.) was determined by agar dilution. MIC(90) values (minimum inhibitory concentration for 90% of the organisms) were 8 microg/mL for Veillonella spp., 4 microg/mL for P. intermedia, 2 microg/mL for P. buccae, 1 microg/mL for Fusobacterium spp. and 0.5 microg/mL for other Prevotella spp. Cidal activity was studied by killing curves with tinidazole and amoxicillin (alone and in combination) at concentrations similar to those achieved in crevicular fluid (41.2 microg/mL tinidazole and 14.05 microg/mL amoxicillin) against an inoculum of ca. 10(7)colony-forming units/mL of four bacterial groups, each one composed of four different strains of the following periodontal isolates: Prevotella spp., Fusobacterium spp. and Veillonella spp. (anaerobes) and one amoxicillin-susceptible Streptococcus spp. (facultative) in a proportion of 1:1:1:1. When only beta-lactamase-negative Prevotella or Fusobacterium strains were tested, significantly higher reductions were found with amoxicillin (>4 log reduction at 48 h) versus controls. The presence of beta-lactamase-positive Prevotella spp. or F. nucleatum strains rendered amoxicillin inactive (no reductions at 48 h), with no differences from controls. Amoxicillin+tinidazole produced >3 log reduction at 24h and >4 log reduction at 48 h regardless of the presence or not of beta-lactamase-positive strains. The presence in crevicular fluid of beta-lactamases produced by beta-lactamase-positive periodontal pathogens may have ecological and therapeutic consequences since it may protect beta-lactamase-negative periodontal pathogens from amoxicillin treatment. In vitro, tinidazole offered high antianaerobic activity against beta-lactamase-positive and -negative periodontal pathogens, avoiding amoxicillin inactivation.

Has the licensing of respiratory quinolones for adults and the 7-valent pneumococcal conjugate vaccine (PCV-7) for children had herd effects with respect to antimicrobial non-susceptibility in invasive Streptococcus pneumoniae?

OBJECTIVES: The aim of the study was to analyse the evolution of antibiotic non-susceptibility in Spanish invasive Streptococcus pneumoniae after licensure of respiratory-quinolones for adults and 7-valent pneumococcal conjugate vaccine (PCV-7) for immunization of children. METHODS: All invasive pneumococci received in the Reference Laboratory (January 2000-August 2007; n = 12 957 isolates) were serotyped, and susceptibility to penicillin/erythromycin/levofloxacin was determined. Antibiotic consumption and PCV-7 doses/year were provided by IMS and the manufacturer, respectively. RESULTS: In 2000-07, PCV-7 distribution (doses/1000 inhabitants

In vitro activity of oral cephalosporins against pediatric isolates of Streptococcus pneumoniae non-susceptible to penicillin, amoxicillin or erythromycin.

The aim of this study was to evaluate the effects of penicillin, amoxicillin or erythromycin resistance on the in vitro activity of oral cephalosporins against Streptococcus pneumoniae pediatric isolates. A total of 282 pediatric isolates received during 2005 in the Spanish Reference Pneumococcal Laboratory were tested by agar dilution: 104 strains were penicillin-susceptible, 72 intermediate, and 106 resistant. Serotypes 9 and 14 were the most troublesome with <10% susceptibility to oral cephalosporins. Cefditoren exhibited the highest intrinsic activity against penicillin/amoxicillin-resistant pneumococci, with MIC(90s )of 0.5 microg/ml, followed by cefotaxime (2 microg/ml), cefpodoxime (4 microg/ml), cefuroxime (16 microg/ml), and cefaclor/cefixime (>or= 32 microg/ml), with 0% susceptibility to cefaclor, cefuroxime and cefpodoxime. Cefditoren 0.5 microg/ml inhibited 95.3%, 95.5%, and 98.6% of penicillin-, amoxicillin-, and erythromycin-resistant isolates, respectively. Susceptibility to oral cephalosporins shifted from >90% in penicillin-susceptible isolates to approximately 38% for cefuroxime/cefpodoxime and approximately 7% for cefaclor in penicillin-intermediate, and to 0% in resistant isolates. Despite the different in vitro activity of oral cephalosporins, full resistance to penicillin or amoxicillin implied lack of susceptibility to all oral cephalosporins with defined CLSI breakpoints, rendering them inadequate as empirical treatment in countries with a high prevalence of penicillin resistance.

Efficacy of cefditoren in the treatment of upper respiratory tract infections: a pooled analysis of six clinical trials.

OBJECTIVE: A pooled analysis of all upper respiratory tract infection studies performed with cefditoren (CDN) was performed. METHODS: Studies were prospective, comparative, multicentre and randomised. Comparators were penicillin V (pharyngitis) and cefuroxime or amoxicillin/clavulanate (sinusitis). A total of 1,322 patients were randomized, 1,241 included in intention-to-treat (ITT) and 1,010 in per-protocol populations (PP) in pharyngotonsillitis studies, and 1,819 randomized, 1,726 included in ITT and 1,589 in PP in acute sinusitis studies. RESULTS: No significant differences in pharyngitis clinical response were found (success rates: 89.4 % to 95.3 %). S. pyogenes eradication was higher with cefditoren at end of therapy (EOT) (90.4% vs. 82.7%; p=0.002) and follow-up (84.7% vs. 76.7%; p=0.008), although no statistically significant (p<0.001). In both groups, clinical failures were significantly higher (p<0.001) in patients showing S. pyogenes persistence than in those showing eradication (> or =98.5% vs. 51.4 %). No differences in sinusitis clinical response were found between CDN and comparators both at EOT (80.2% vs. 84.8%) and at end of follow-up (71.2% vs. 77.4%). CONCLUSION: Cefditoren had similar point estimates of clinical efficacy to comparators in pharyngotonsillitis and sinusitis, and a tendency to higher S. pyogenes eradication in pharyngotonsillitis.

Cidal activity of oral third-generation cephalosporins against Streptococcus pneumoniae in relation to cefotaxime intrinsic activity.

This study explores the killing kinetics within 12 h of four oral third-generation cephalosporins against ten Streptococcus pneumoniae strains exhibiting cefotaxime minimum inhibitory concentrations (MICs) from 0.03 to 2 microg/ml. Killing curves were performed with concentrations achievable in serum after standard doses (0.015-4 microg/ml). Reductions of 90% were achieved with all compounds at serum-achievable concentrations for strains exhibiting cefotaxime MIC < or = 0.5 microg/ml. Against strains with cefotaxime MIC > or = 1 microg/ml, only cefditoren reached a 90% reduction with concentrations of 0.5-1 microg/ml doses. At 4 microg/ml, cefditoren and cefotaxime reached 99.9% reduction in seven of the ten strains studied. At serum-achievable concentrations, cefdinir and cefixime were not bactericidal against strains exhibiting cefotaxime MIC > or = 0.25 microg/ml and > or = 0.5 microg/ml, respectively. Cefditoren showed the best killing kinetic profiles and this observation may be important when choosing an oral third-generation cephalosporin as initial or sequential therapy.

Strong slime production is a marker of clinical significance in Staphylococcus epidermidis isolated from intravascular catheters.

Biofilm production was assessed in 52 Staphylococcus epidermidis isolates from the catheters of 52 patients with catheter-related bloodstream infections (CR-BSI) and compared with 14 isolates from the skin of healthy volunteers by spectrophotometry. The isolates were classified as non- (G1), weak- (G2) or strong- (G3) slime producers based on optical density, and as producers and non-producers based on the results of the Congo red agar test. Differences (p = 0.012) in the proportion of G1, G2 and G3 among the isolates were found between catheter and healthy skin strains: there was a higher percentage of G1 types among the healthy skin strains (35.7 vs. 11.5%; p = 0.046) and a higher percentage of G3 types among the catheter isolates (44.2 vs. 0%; p = 0.001). No significant differences were found with the Congo red agar test. G3 is a phenotypic marker for CR-BSI.

Influence of penicillin/amoxicillin non-susceptibility on the activity of third-generation cephalosporins against Streptococcus pneumoniae.

To study the influence of penicillin/amoxicillin non-susceptibility on the activity of third-generation cephalosporins, 430 consecutive penicillin non-susceptible Streptococcus pneumoniae 2007 isolates received in the Spanish Reference Pneumococcal Laboratory were tested. For comparative purposes, 625 penicillin-susceptible 2007 isolates were also tested. Susceptibility was determined by agar dilution using Mueller-Hinton agar supplemented with 5% sheep blood. Penicillin-susceptible strains were susceptible to amoxicillin, cefotaxime and ceftriaxone, 99.8% to cefpodoxime and 99.5% to cefdinir, and were inhibited by 0.12 microg/ml of cefditoren and 4 microg/ml of cefixime. Penicillin-intermediate strains were susceptible to cefotaxime and ceftriaxone, with <50% susceptibility to cefdinir and cefpodoxime. The MIC(50) and MIC(90) values of cefditoren were 0.25 microg/ml and 0.5 microg/ml, respectively, whereas cefixime exhibited only marginal activity (MIC(90)=16 microg/ml). Penicillin-resistant strains were resistant to cefdinir and cefpodoxime, with 74.8% and 94.1% susceptibility to cefotaxime and ceftriaxone, respectively. Cefditoren MIC(50)/MIC(90) (0.5/1 microg/ml) were lower than cefotaxime and ceftriaxone. Among amoxicillin non-susceptible strains, susceptibility to cefdinir and cefpodoxime was <10%, and susceptibility to cefotaxime decreased from 87.9% in the intermediate category to 63.0% in the resistant group. Cefditoren MIC(50)/MIC(90) (0.5/1 microg/ml) were lower than cefotaxime. In conclusion, the activity of cefixime, cefdinir and cefpodoxime was highly affected by penicillin/amoxicillin non-susceptibility, while parenteral third-generation cephalosporins exhibited higher intrinsic activity (MIC(90)=1 microg/ml for penicillin-resistant and 2 microg/ml for amoxicillin-resistant strains). Cefditoren exhibited one-dilution lower MIC(90) values for these strains, even against those of the most troublesome serotypes.