[Recommendations in the empiric anti-infective agents of intra-abdominal infection]. / Recomendaciones en el tratamiento antibiótico empírico de la infección intraabdominal.

A significant number of patients with abdominal infection develop advanced stages of infection and mortality is still above 20%. Failure is multifactorial and is associated with an increase of bacterial resistance, inappropriate empirical treatment, a higher comorbidity of patients and poor source control of infection. These guidelines discuss each of these problems and propose measures to avoid the failure based on the best current scientific evidence.

[Anidulafungin]. / Anidulafungina.

Anidulafungin is a new echinocandin antifungal agent recently approved in Spain by the Spanish Drug Agency. As other echinocandins, it inhibits a selective target, 1,3- beta-D-glucan synthesis, a major structural component of the fungal cell wall which is not present in mammalian cells, this avoiding toxicity problems. It has fungicidal activity against many Candida spp., including fluconazole-resistant, and fungistatic activity against other yeast and moulds such as Aspergillus spp. Clinical trials have shown non-inferiority of anidulafungin to fluconazole for invasive, including candidemia, and non-invasive Candida infections. It is well-tolerated, and no drug-related serious adverse events have been reported. Anidulafungin, which has a very long half life, is slowly degraded by human peptidases and proteases and has a low drug-drug interaction profile based on its lack of interaction with the cytochrome P450 system. Thus, dosing adjustments of anidulafungin based on age, gender, body weight, disease status, concomitant therapy or renal or hepatic insufficiency is not necessary. As it does not interact with amphotericin B and voriconazole, cyclosporine, tacrolimus and other drugs, it can be used in combination with other antifungal agents and co-administered with immunosuppressant drugs. It is generally well-tolerated in clinical trials. Its most frequent adverse events are nausea, vomiting, moderate diarrhea, transient elevation of hepatic enzymes and headache. Some of the patients have mild, passing reactions such as facial blushing, nausea and dyspnea related with rapid intravenous perfusion. Its antifungal activity, clinical efficacy, safety profile, and pharmacokinetic characteristics make it a suitable alternative antifungal compound for therapy of mucosal candidiasis, candidemia and invasive candidiasis, above all in patients with some degree of renal and hepatic insufficiency.

[Recommendations of antifungal treatment in patients with low grade immunosuppression]. / Recomendaciones de tratamiento antifúngico en pacientes con bajo grado de inmunodepresión.

Because of the relevance that the systemic mycoses has acquired in non-highly immunocompromised patients, the treatment difficulties they have due to the increase of the non-albicans Candida species and the need to have a better and more rational use of the new antifungal agents (voriconazole, posaconazole, caspofungin, anidulafungin and micafungin), an experts' panel on infectious diseases in representation of the Spanish Society of Chemotherapy, Spanish Society of Internal Medicine, and Spanish Society of Pneumology and Thoracic Surgery has met in order to make a few recommendations based on the scientific evidence in an effort to improve their efficiency.

[Epidemiology of genotypic resistance of HIV-1 in Valencia. A 4-year study]. / Epidemiología de las resistencias genotípicas del VIH-1 en Valencia. Estudio de cuatro años.

HIV resistance to antiretroviral drugs was studied in 348 samples taken from patients at the Molecular Biology Unit of the Microbiology Department of the Hospital La Fe, from January 2003 to July 2007. Once the viral load in plasma was determined, resistance was detected using complete gene sequencing for protease up to position 3464 of the HIV-1 reverse transcriptase gene. The results were analyzed using the Omiga 1.2 (Oxford Molecular Group) and HIV db Genotypic Resistance Interpretation Algorithm Version 4.3.0 (Stanford University) programs. The drugs least affected by the presence of mutations leading to resistance were the protease inhibitors darunavir, tripanavir and lopinavir (sensitivity >80%), the nucleoside reverse transcriptase inhibitors tenofovir and lamivudine (sensitivity >90%) and the non-nucleoside reverse transcriptase inhibitor TMC125 (sensitivity >80%).

[The fungicidal activity and paradoxical effect of caspofungin against yeast. Influence of culture medium and incubation time]. / Actividad fungicida y efecto paradójico de la caspofungina sobre levaduras. Influencia del medio de cultivo y el tiempo de incubación.

The effect of culture medium and incubation time on the fungicidal activity of caspofungin and on the frequency of paradoxical effect has been studied in 144 blood culture isolates (42, Candida tropicalis, 32 Candida glabrata, 21 Candida krusei, 20 Candida parapsilosis, 11 Candida guilliermondii, 4 Candida famata, 3 Candida lusitaniae, 3 Blastoschizomyces capitatus, 2 Saccharomyces cerevisiae, 2 Yarrowia lipolytica, 1 Candida inconspicua, 1 Candida lambica, 1 Candida sake y 1 Pichia ohmeri). The media assayed were standard RPMI 1640, Antibiotic Medium #3 (AM#3) and AM#3 with 2% of dextrose (AM#3-G). MIC(2) (>or= 50% growth inhibition) and MIC(0) (100% inhibition) at 24 and 48h and the minimum fungicidal concentration (MFC) were determined. The greatest activity of caspofungin was obtained in AM#3 medium followed by AM#3-G and RPMI. Geometric means (GM) MIC(2) at 24/48 h incubation were 0.06/0.12, 0.1/0.2 and 0.65/0.89 mg/l, respectively. GMMIC(0) was 0.1/0.17 (AM#3), 0.16/0.25 (AM#3-G) and 1.06/1.7 mg/l (RPMI). Caspofungin showed fungicidal activity in the three media (GM-MFC, 0.28, 0.38 and 3 mg/l in AM#3, AM#3-G and RPMI, respectively). The percentage of caspofungin tolerant isolates (MFC >or=8 x MIC(0)) was 8.09% (AM#3), 8.3% (AM#3-G) and 13.9% (RPMI). RPMI was the medium less affected by the incubation time and AM#3 the most affected (93.7 and 78.2% of isolates the MIC(2) increased or=2 mg/l (AM#3) and >or=4 mg/l (AM#3-G). The highest frequency was obtained in RPMI medium and C. tropicalis species and the lowest frequency for C. krusei y C. glabrata.

[In vitro activity of ertapenem against clinical bacterial isolates in 69 Spanish medical centers (E-test study)]. / Actividad in vitro de ertapenem frente a cepas bacterianas clínicas aisladas en 69 centros médicos españoles (Estudio E-test).

This study was conducted to assess the in vitro activity of ertapenem against clinical bacterial isolates from patients with community-acquired intra-abdominal and lower tract respiratory infections in Spain in 2003. As the study was conducted before the marketing of ertapenem, it was also useful to define a baseline susceptibility pattern for ertapenem in each of the participating hospitals for later surveillance studies. Each partipating site identified a variable number of aerobic and facultative bacteria isolated from patients with community-acquired intra-abdominal infection or pneumonia using standard procedures. E-test strips were used for determining the minimum inhibitory concentration (MIC) of ertapenem, while for other antimicrobials either quantitative dilution techniques or qualitative diffusion procedures were used according to each microbiology laboratory's routine practice. MIC breakpoints for categorization of susceptibility provided by the CLSI were used for interpreting MIC values. A total of 2,901 recent clinical isolates from patients with community-acquired intra-abdominal infection or pneumonia hospitalized in 69 Spanish medical centers were tested. These isolates included 2,039 Gram-negative bacteria (1,646 Enterobacteriaceae, 216 Haemophilus, 123 non-fermenting Gram-negative bacteria [NFGNB] and 54 others) and 862 Gram-positive bacteria (556 pneumococci, 159 staphylococci, 96 streptococci other than S. pneumoniae, 44 enterococci and 7 others). Ertapenem was very active in vitro against Enterobacteriaceae (99.8% susceptible), Haemophilus (96.3% susceptible), pneumococci (99.6% susceptible, of which 31% were penicillin non-susceptible strains), streptococci other than S. pneumoniae (99.0% susceptible) and methicillin-susceptible staphylococci (94.8% susceptible). For other Gram-positive and Gram-negative pathogens for which ertapenem susceptible breakpoints have not been defined, MIC(90) values were 0.38 and 0.064 mg/l, respectively. As expected, ertapenem had minimal activity in vitro against NFGNB, enterococci and methicillin-resistant staphylococci (MIC(90) of >32 mg/l for all three). Ertapenem was highly active in vitro against most bacteria isolated from patients with community-acquired intra-abdominal and lower respiratory tract infections.

Quinolone resistance in female outpatient urinary tract isolates of Escherichia coli: age-related differences.

During a 1-year period, from November 2003 to October 2004, urinary Escherichia coli isolates were collected from 20 clinical microbiology laboratories across Spain. The main objective was to assess the resistance of E. coli to the antimicrobials most commonly prescribed for community-acquired urinary tract infections depending on the patient's age. A total of 2,230 valid E. coli strains from female outpatients were isolated and sent to a single central reference laboratory for confirmation and susceptibility testing using an agar dilution method. A two-sided chi-squared test was used to assess the differences in resistance between age groups (< or =65 and >65 years). E. coli resistance was found to be more common to ampicillin (52.1%), cotrimoxazole (26%) and quinolones (18%), whereas resistance to amoxicillin-clavulanic acid, cefuroxime axetil and fosfomycin were below 3%. In women older than 65 years, resistance to ciprofloxacin reached up to 29% compared with 13% of those in the under 65 age group (p <0.001). For cotrimozaxole, rates were 32% vs. 23% (p <0.001) and for ampicillin 56% vs. 50% (p=0.02), respectively. It was concluded that fosfomycin, amoxicillin-clavulanic acid and cefuroxime axetil are the most suitable antimicrobials for empirical treatment in Spain given the high 18% and 26% resistance rates to quinolones and cotrimoxazole, respectively. Being older than 65 years of age was associated with higher resistance rates to ciprofloxacin (29%). These results should be considered when recommending empirical therapy for acute cystitis in women.

Antimicrobial susceptibility of clinical Escherichia coli isolates from uncomplicated cystitis in women over a 1-year period in Spain.

High usage of antibiotics in Spain has led to an increase in resistance in urinary Escherichia coli isolates in different geographic regions. The problem of resistance in urinary E. coli in Spain was investigated by gathering a large number of isolates from 20 different sites nationwide over a 1-year period from November 2003 to October 2004 in a large population of women. The objectives of this study were to assess the resistance to the antibiotics most commonly prescribed for community-acquired urinary tract infections (UTIs), according to age and different geographical areas of Spain, and to evaluate the potential association between geographical differences in quinolone consumption and resistance to E. coli. A total of 2,292 valid E. coli strains from female outpatients were isolated and sent to a single central reference laboratory for confirmation and susceptibility testing. Of these, 2,230 isolates were available for the age analysis. A two-sided chi2 test was used to identify differences in resistance between age groups. Antibiotic units per province were purchased from IMS and consumption was expressed in units per 1,000 people per year. Univariate correlation (Pearson coefficient) between resistance to ciprofloxacin and quinolone consumption was calculated using a two-sided p-value. Resistance shown by E. coli was more common to ampicillin (52.1%) and cotrimoxazole (26%), followed by quinolones (18%), whereas resistance to amoxicillin-clavulanic acid, cefuroxime-axetil and fosfomycin was less than 3%. In the subgroup of women aged >65 years, resistance to ciprofloxacin was 29% compared to 13% for the subgroup of women <65 years (p<0.001). For these same subgroups, resistance rates were 32% vs. 23% for cotrimoxazole (p<0.001) and 56% vs. 50% for ampicillin (p=0.02), respectively. Statistically significant correlations were found between consumption of quinolones and E. coli resistance to ciprofloxacin (r=0.5; p=0.025). Resistance of E. coli isolates to quinolones varied significantly according to geographical areas, ranging from a high of 16.5% and 16.6% in the southern and eastern regions of Spain, respectively, to a low of 8% in the north in women aged <65 years. Additionally, the susceptibility to quinolones of E. coli isolates recovered from women aged >65 years was significantly lower across all regions of Spain than that of isolates recovered from younger women. Fosfomycin, amoxicillin/clavulanic acid and cefuroxime-axetil are the most suitable antibiotics for empirical treatment in Spain given the high 18% and 26% resistance rates to quinolones and cotrimoxazole, respectively. Higher resistance rates to ciprofloxacin were associated with being aged 65 years and over. These data need to be considered when recommending empirical therapy for acute cystitis.

In vitro activity of linezolid in combination with doxycycline, fosfomycin, levofloxacin, rifampicin and vancomycin against methicillin-susceptible Staphylococcus aureus.

The objective of this paper was to investigate the in vitro effects of linezolid combined with five antistaphylococcal antibiotics--doxycycline, fosfomycin, levofloxacin, rifampicin and vancomycin--upon methicillin-susceptible Staphylococcus aureus (MSSA). Five MSSA isolates from clinical specimens of human infections--hf008, hf095, hf295, hf602 and hf946--were used in this study. The checkerboard method was used to assess synergism between linezolid and the five antibiotics, and time-kill curves were carried out with the most active combinations. Indifference was the most common result achieved by the checkerboard method when linezolid was combined with rifampicin, vancomycin or doxycycline. The combination with levofloxacin yielded antagonism for two of the five isolates. However, four isolates showed synergy for the combination of linezolid plus fosfomycin with a fractional inhibitory concentration index (FICI) > or = 0.5. Neither linezolid nor fosfomycin alone inhibited growth at 1/4x minimum inhibitory concentration (MIC); but the combination of both drugs at 1/4 the respective MIC showed a synergistic bacteriostatic effect, a 2-3 log(10) decrease with respect to the most active antibiotic alone. In summary, the combination of subinhibitory.

[In vitro activity of voriconazole against yeast and algae isolates according to new resistance pattern cut-off points]. / Actividad in vitro del voriconazol frente a levaduras y algas con los nuevos puntos de corte del patrón de resistencia.

Voriconazole is a second-generation triazole derived from fluconazole but with greater potency and spectrum of activity, showing good in vitro activity against Candida, Cryptococcus and Aspergillus species, and other filamentous and dimorphic fungi. It can be administered orally or intravenously. It was initially approved in 2002 by the U.S. Food and Drug Administration as a treatment option for invasive aspergillosis and Fusarium and S. apiospermum infections showing resistance or intolerance to other antifungals; later on, it also received approval in the United States and Europe as a treatment option for esophageal candidiasis; candida infection in non-neutropenic patients; disseminated candidiasis of skin, abdomen, kidney and bladder; and injuries. Recently, the Clinical Laboratory Standard Institute established some provisional break points for voriconazole, classifying isolates with an MICor=4 mg/l as resistant. In line with these new data, we performed a systematic review of literature on in vitro activity of voriconazole against yeast and algae isolates, and compared it to that of fluconazole and itraconazole. The review included a total of 27,340 yeast isolates, 24,177 of Candida species, 2,726 of Cryptococcus species, 453 of other species, and 104 Prototheca. The yeast isolates resistant to voriconazole is approximately 1%, and 71% of fluconazole-resistant isolates are susceptible to voriconazole.

[Patterns of susceptibility to antibiotics of Enterobacteriaceae causing intra-abdominal infection in Spain: SMART 2003 study outcomes]. / Patrones de sensibilidad a antimicrobianos de Enterobacteriaceae causantes de infecciones intraabdominales en España: resultados del estudio SMART 2003.

SMART (Study for Monitoring Antimicrobial Resistance Trends) is an ongoing global antimicrobial surveillance program focused on clinical isolates from intra-abdominal infections. The objective of this subanalysis was to assess antimicrobial susceptibility patterns among Entero-bacteriaceae recovered at 13 participating Spanish sites during 2003. Antimicrobial susceptibility testing was performed using broth microdilution techniques according to the CLSI (formerly NCCLS) guidelines for MIC testing. The presence of extended-spectrum beta-lactamases (ESBL) was confirmed in isolates with a MIC of ceftriaxone, ceftazidime, or cefepime>or=2 mg/l by comparing cefepime MICs with and with-out clavulanate. A total of 981 Enterobacteriaceae recovered from 840 patients were tested, of which 398 (41%) were community-acquired. Escherichia coli was the most common isolate (571 isolates; 58%), followed by Klebsiella spp. (153; 16% Enterobacter spp. (97; 10%), and Proteus spp. (63; 6%). A total of 191 isolates (19%) from 176 patients produced inducible beta-lactamases. The carbapenems and amikacin were the most consistently active agents against the Enterobacteriaceae (susceptibility>or=99%). Resistance rates for ceftazidime, cipro-floxacin, and levofloxacin exceeded 10%. ESBLs were detected phenotypically in 61 (6%) isolates, being the most common E. coli (61%), Klebsiella spp. (20%), and Enterobacter spp. (8%). Antimicrobial resistance among Enterobacteriaceae isolated from intra-abdominal infections is a problem in Spain. A significant proportion of inducible beta-lactamase and ESBL-producing Enterobacteriaceae causing intra-abdominal infection were acquired in the community. The carbapenems ertapenem, imipenem and meropenem and the aminoglycoside amikacin were highly active in vitro against Enterobacteriaceae isolated from intra-abdominal sites, including ESBL-producing organisms.

[In vitro susceptibility to antibiotics and the most common Streptococcus pneumoniae serotypes: a multicenter study]. / Sensibilidad in vitro a los antibióticos y serotipos más frecuentes de Streptococcus pneumoniae. Estudio multicéntrico.

The susceptibility and serotypes of 211 strains of Streptococcus pneumoniae collected from 12 Spanish hospitals in December 2003 were studied. Susceptibility tests for eight antibiotics were carried out by E-test, and the serotype classification was carried out using pneumococcus antiserum from the Copenhagen Statens Serum Institute. Overall, the most frequent serotypes were 19 (12.2%); 6 (10.7%); 23 (10.2%); 3 (8.1%); 9 (6.6%); 14 (6.1%); and 29 (5.1%). In blood, the most frequent were 19 (16.6%) and 14 (11.9%), and 8.6% were nontypable. Under NCCLS (M7-A5) criteria, 55.6% of the strains were susceptible to penicillin (MIC < or =0.06 mg/l) and 7.9% showed high resistance (MIC > or =2 mg/l). Susceptibility to other antibiotics was 98% to moxifloxacin; 97.1% to levofloxacin; 94.6% to amoxicillin-clavulanic acid; 71.2% to cefuroxime; 84.4% to ceftriaxone; and 63.1% to clarithromycin and azithromycin. Only 13.3% of the strains showed susceptibility to the antibiotics tested. The greatest percentage of strains resistant to other antibiotics was found among the strains resistant to penicillin. Nine resistant phenotypes were detected.

[Activity of voriconazole against yeasts isolated from blood culture determined by two methods]. / Actividad del voriconazol sobre levaduras aisladas de hemocultivo determinada por dos métodos.

The in vitro activity of voriconazole has been determined by two methods: the reference M27-A2 and the marketed Sensititre YeastOne microdilution colorimetric method. The agreement (+/-2 dilutions) and correlation between methods as well as the percentage of errors has been determined. A total of 144 yeasts (47 Candida albicans, 52 C. parapsilosis, 13 C. tropicalis, 10 C. krusei, 9 C. glabrata, 2 C. guilliermondii, 1 C. colliculosa, 1 C. dubliniensis, 2 Trichosporum asahii, 1 T. mucoide, 1 Trichosporum spp., 1 Kloakera apis, 2 Pichia ohmeri, and 2 Rhodotorula glutinis) isolated from blood culture between October 2002 and May 2005 were assayed. Voriconazole has shown good in vitro activity. The rate of voriconazole-susceptible (MIC < or =1 mg/l) strains was 97% and the MIC90 0.25 mg/l by the two methods. The overall percentage of agreement between methods was 86% (range 44.23-100%) and the Pearson's coefficient of correlation was 0.961. Categorical agreement was strain dependent and ranged from 84.6% for emergent yeasts to 100% for the other species tested except for C. glabrata (66.6%). No major or very major errors were found, the percentage of minor errors being 1.38%. Only one C. tropicalis and one C. glabrata strain were resistant (MIC > or =4 mg/l) to voriconazole (1.38%) by the reference method. The colorimetric method identified the voriconazole-resistant C. tropicalis strain, and classified the C. glabrata as susceptible-dose dependent. The colorimetric method is a potential alternative method for testing the susceptibility of yeast in a clinical laboratory and identifies the susceptible strains (100% agreement) very well. Nevertheless, further studies including more voriconazole-resistant strains are required to determine the ability of the method to identify resistance, which is the goal of susceptibility tests.