In vitro activity of fosfomycin trometamol against pathogens from urinary tract infections: a Spanish multicenter study.

The in-vitro susceptibilities of a total of 1371 urinary tract pathogens to fosfomycin trometamol were determined. According to the NCCLS breakpoints, Enterobacteriaceae and gram-positive microorganisms were, in general, very sensitive to this antimicrobial. More than 90.0% of the Escherichia coli and Citrobacter spp. and more than 70.0% of the Klebsiella pneumoniae, K. oxytoca, Enterobacter spp., Proteus mirabilis, Staphylococcus aureus, coagulase-negative staphylococci and Enterococcus spp. strains tested were susceptible to fosfomycin trometamol. However, Pseudomonas aeruginosa and Acinetobacter spp. strains were more resistant. In general, recent clinical isolates from urinary tract infections (UTIs) in both community and hospital were also very sensitive (> 80.0%) to fosfomycin, its activity being higher than that of the rest of the antimicrobials commonly used for therapy of uncomplicated UTIs. More than 75.0% of the most frequently isolated pathogens from UTIs, except for P. aeruginosa (31.8%) and Acinetobacter spp. (11.1%), were susceptible to fosfomycin trometamol. The results obtained in this study, together with the infrequency of side effects and its pharmacokinetic properties, indicate that fosfomycin trometamol may be a useful alternative for single-dose therapy of uncomplicated UTIs.

[Evaluation of Mycobacterium fortuitum acyltrehaloses in the serologic diagnosis of pulmonary tuberculosis]. / Evaluación de aciltrehalosas de Mycobacterium fortuitum en el diagnóstico serológico de tuberculosis pulmonar.

BACKGROUND: Several glycolipids of Mycobacterium tuberculosis are antigenic and their use in the serodiagnosis of pulmonary tuberculosis has been postulated. Acyltrehaloses (SL-IV) are among the strongest antigenic glycolipids of M. tuberculosis; similar compounds have been found in M. fortuitum. The aim of the present study was to evaluate the usefulness of the acyltrehaloses of M. fortuitum in the serodiagnosis of pulmonary tuberculosis. METHODS: Two glycolipids, identified as triacyl- (TAT-MF) and diacyl- (DAT-MF) trehaloses, were studied by an ELISA method. Two independent analyses were carried out. In the first one, IgG and IgM were determined in sera from patients with pulmonary tuberculosis (84-24 bacteriologically not confirmed--), healthy individuals (46) and patients with respiratory pathologies other than pulmonary tuberculosis (38), using TAT-MF. In the second one, IgG was determined in sera from pulmonary tuberculosis patients (34) and from healthy individuals (20), using DAT-MF. RESULTS: The sensitivity of the IgG ELISA using TAT-MF varied, according to the cut-off point, between 79.8 and 39.3%; the specificity values ranged between 83.3 and 98.8%. In sera from bacteriologically not confirmed pulmonary tuberculosis patients the sensitivity was 87.5-45.8%. The sensitivity for IgM was very low using TAM-MF (10.7-2.3%), with specificity values ranging from 77.4 to 100%. The sensitivity and specificity values of IgG using DAT-MF were, respectively, 34.3-9.3% and 90-100%. CONCLUSIONS: The IgG ELISA using TAT-MF has similar values of sensitivity and specificity to those reported for the acyltrehaloses of M. tuberculosis, although this antigen, by itself, can not be used in the serodiagnosis of pulmonary tuberculosis. DAT-MF has no value in the serodiagnosis of pulmonary tuberculosis.

Treatment with various antibiotics of experimental endocarditis caused by penicillin-resistant Streptococcus sanguis.

BACKGROUND: Streptococcus sanguis currently accounts for one-half of viridans streptococci. Treatment has become complicated due to the increase in resistance to penicillin and cephalosporins. The aim of the study was to assess the efficacy of various antibiotics as monotherapy and in association with gentamicin, in a experimental model of infective endocarditis in rabbits. The effects were compared with a control group and a group given classical penicillin-gentamicin treatment. MATERIAL AND METHODS: Infective endocarditis was induced in 180 rabbits with a clinical isolate of Streptococcus sanguis. Treatment was started 48 h after infection, and lasted 5 days. The animals were divided into nine groups of 20 rabbits: G1, untreated controls; G2, penicillin-gentamicin; G3, clindamycin-gentamicin; G4, imipenem; G5, imipenem-gentamicin; G6, teicoplanin; G7, teicoplanin-gentamicin; G8, vancomycin and G9, vancomycin-gentamicin. Response to therapy was evaluated by mortality curves, as negative blood cultures, concentration of S. sanguis in aortic vegetations and rate of sterilization of vegetations. RESULTS: Vegetation weight was significantly lower in treated groups than in controls; lower weights were found in G5, 6, and 9. G9 sterilized 75% of the vegetations. Death occurred in 25% of the control group and in 4.76% of G6 and 7. Blood cultures became negative most rapidly in G9. CONCLUSIONS: Combined treatment with vancomycin-gentamicin may be highly efficacious in patients with endocarditis caused by penicillin-resistant Streptococcus sanguis. Other combinations, such as imipenem-gentamicin and teicoplanin-gentamicin, may be also advantageous.

A family of diacyltrehaloses isolated from Mycobacterium fortuitum.

A trehalose-containing glycolipid was detected in several strains of Mycobacterium fortuitum and characterized as 2,3-di-O-acyltrehalose (DAT) by combined NMR spectroscopy, IR spectroscopy, GLC and GLC-MS. Lipid constituents of the molecule were identified as a mixture of straight-chain (14-18 carbon atoms) and methyl-branched-chain (17-21 carbon atoms) fatty acyl groups. DAT was further fractionated by reverse phase TLC into four fractions that were designated DAT-I-DAT-IV. DAT-I contained 70-75% straight-chain acyl substituents (hexadecanoyl and octadecanoyl predominating) and 25-30% 2-methyl branched substituents (mainly 2-methyl octadecadienoyl). DAT-II was composed of a mixture in which the acyl groups were almost exclusively 2-methyl branched, with 2-methyl octadecadienoyl and 2-methyl octadecen-2-oyl predominating. DAT-III, which was the major isolated fraction, consisted of compounds in which the ratio linear to branched acyl groups varied between 0.8 to 0.9, 2-methyl octadecen-2-oyl, hexadecanoyl and octadecanoyl being the most abundant. Finally, DAT-IV comprised a mixture of DAT molecules containing mostly 2-methyl octadecadienoyl, 2-methyl octadecen-2-oyl, 2-methyl eicosadienoyl and 2-methyl eicosen-2-oyl groups.

Treatment with imipenem of experimental endocarditis caused by penicillin-resistant Streptococcus sanguis.

The efficacy of imipenem alone or in combination with gentamicin for the treatment of experimental endocarditis in rabbits caused by a penicillin resistant strain of Streptococcus sanguis was compared to that of gentamicin and penicillin G. In vitro, both beta-lactams were bactericidal in action and the combination of gentamicin and imipenem was synergistic after 4 h whereas penicillin G and gentamicin showed synergy after 8 h. Antibiotic treatment was started two days after initiating infection and groups of 20 animals were treated for 5 days with imipenem alone or in combination with gentamicin or with gentamicin and penicillin G. Two of 20 rabbits which received no therapy died whereas all other rabbits survived the treatment period. Blood cultures became negative in 19 rabbits on the second day of treatment with imipenem and gentamicin and sterilization of the vegetations was achieved in 12 animals. In contrast, eight animals given the alternative treatments remained bacteraemic and viable organisms were recovered from the vegetations in every case. However, bacterial counts and vegetation weights only differed significantly between treated animals and controls but not between the different treatment groups. Never the less, these data suggest that combined treatment with imipenem and gentamicin might provide an effective regimen for patients with endocarditis caused by penicillin resistant S. sanguis.

Treatment of experimental endocarditis caused by penicillin-resistant Streptococcus sanguis with different doses of teicoplanin.

Streptococcus viridans continues to be the most frequent causal agent of infective endocarditis. Treatment has become more complicated due to the increase in resistance to penicillin and cephalosporins. In order to study the possible efficacy of teicoplanin at low and high doses, this antibiotic was investigated in rabbits as a monotherapy and in association with gentamicin. The effects were compared with a control group and a group given classical penicillin-gentamicin treatment. Infective endocarditis was induced in 120 rabbits with a clinical isolate of Streptococcus sanguis. Treatment was started 48 h after infection, and lasted 5 days. Animals were divided into 6 groups of 20 rabbits each: G1, untreated controls; G2, penicillin+gentamicin; G3 low-dose teicoplanin; G4, low-dose teicoplanin+gentamicin; G5, high-dose teicoplanin; and G6, high-dose teicoplanin+gentamicin. Response to therapy was evaluated with mortality curves, negativization of blood cultures, concentration of S. sanguis in aortic vegetations and rate of sterilization of vegetations. Vegetation weight was significantly lower in treated groups than in controls; lower weights were found in G4, the only treatment that sterilized 65% of vegetations. Death occurred only in the control group (10% mortality). Negativization of blood cultures was greatest and most rapid in G4, followed by G6. Concentrations of S. sanguis in aortic vegetations were significantly lower in all treated groups compared with controls, with the lowest being in groups G4 and G6. Combined treatment with teicoplanin+gentamicin may be highly efficacious in patients with endocarditis caused by penicillin-resistant Streptococcus sanguis. High-dose teicoplanin+gentamicin does not seem to be more efficacious than low-dose teicoplanin+gentamicin.

[Microbiological study via occluded telescopic catheter in patients under mechanical ventilation and suspected of pneumonia. Clinico-bacteriological follow up of the cases]. / Estudio microbiológico mediante catéter telescópico ocluido en pacientes bajo ventilación mecánica y sospecha de neumonía. Seguimiento clínico-bacteriológico de los casos.

Pneumonias related to mechanical ventilation pose a serious diagnostic challenge and are responsible for elevated mortality. Conventional diagnostic methods are of little help. The introduction of invasive techniques such as bronchial catling via an occluded telescopic catheter (OTC) has proven to be an important advance in diagnosis and therapy. We have compared the bacteriological results obtained using OTC with those using conventional diagnostic methods such as tracheobronchial pumps (TBP) and hemocultures, and we have undertaken a bacteriological, clinical follow-up of the cases. Seventy-four patients under mechanical ventilation and suspected of pneumonia were under study. The study consisted to two consecutive phases of collecting bacteriological samples throughout the patient's evolution. A total of 121 fibrobronchoscopies were performed. The sensitivity obtained with OTC was 76%, and the specificity was 100%. The two techniques, OTC and TBP, coincided in 38% of the cases. According to the bacteriological results obtained with OTC, the antibiotic treatment was modified in 44.5% of the patients. The sensitivity of the OTC was significantly less in those patients were the last doses of antibiotic was administered within two hours of performing the procedure. The procedure of gathering secretions from the inferior respiratory tract with OTC possesses greater sensitivity and diagnostic specificity in patients with mechanical ventilation and pulmonary infiltrates and improves the diagnosis performed by other conventional and routine techniques such as TBA and hemocultures.

[Right endocarditis caused by Staphylococcus aureus in parenteral drug addicts: evaluation of a combined therapeutic scheme for 2 weeks versus conventional treatment]. / Endocarditis derecha por Staphylococcus aureus en adictos a drogas por vía parenteral: valoración de un régimen terapéutico combinado de 2 semanas frente al tratamiento convencional.

BACKGROUND: Intravenous drug addicts (IVDA) are a group of patients in whom it is difficult to complete standard treatment of infectious endocarditis due to frequent antisocial behavior and in whom, once clinical improvement is achieved, voluntary discharge is frequently requested. This is why the evaluation of new treatment schedules tending to decrease the length of the same is of great interest. This non randomized study has the aim of knowing the efficacy of a short treatment with cloxacillin or vancomycin associated to gentamicin in right-sided endocarditis by methicillin-sensitive Staphylococcus aureus, comparing this with the standard schedule of 28 days. METHODS: This series was made up of IVDA patients diagnosed of right endocarditis by S. aureus. Inclusion criteria were the presence of intravenous drug addiction, isolation of methicillin-sensitive S. aureus in 2 or more blood cultures and achievement of the diagnostic criteria of right-sided endocarditis. Two schedules were used: a) standard: cloxacillin or vancomycin for 4 weeks, associating aminoglucoside in the first 3-5 days; b) short; cloxacillin or vancomycin associated to gentamicin for 2 weeks with no ulterior treatment. The study was not randomized and the treatment of 2 weeks was compared with historic controls treated for 4 weeks. The criteria evaluated were those of clinical cure, relapse, appearance of complications during treatment and mortality. RESULTS: Both the standard treatment and the combination of cloxacillin or vancomycin with gentamicin for 2 weeks cured 100% of the episodes of right endocarditis by S. aureus. There were no relapses and mortality was nul. Neither were there any differences between the two groups with regard to appearance of complications. CONCLUSIONS: In intravenous drug addict patients with right-sided endocarditis by methicillin S. aureus, the association of cloxacillin and gentamicin for 2 weeks is an effective alternative to long (4 week) treatments with only one antibiotic. The low number of cases treated with vancomycin does not allow conclusions to be drawn on its efficacy.

[Treatment with vancomycin of experimental endocarditis caused by Streptococcus sanguis II resistant to penicillin]. / Tratamiento de endocarditis experimental por Streptococcus sanguis II resistente a penicilina con vancomicina.

BACKGROUND: Streptococcus viridans continues to be the most frequent causal agent of infective endocarditis. Treatment has become more complicated due to the increase in resistance to penicillin and cephalosporins. In order to study the possible efficacy of vancomycin, this antibiotic was investigated in rabbits as a monotherapy and in association with gentamicin. The effects were compared with a control group and a group given classical penicillin-gentamicin treatment. MATERIAL AND METHODS: Minimum inhibitory concentration, minimum bactericidal concentration, lethality curves and synergism were determined against Streptococcus sanguis II. Infective endocarditis was induced in 80 rabbits, which were infected via catheter. Treatment was started 48 hours after infection, and lasted 5 days. The animals were divided into 4 groups of 20 rabbits each: 1, untreated controls; 2, penicillin-gentamicin; 3, vancomycin; 4, vancomycin-gentamicin. Response to therapy was evaluated with mortality curves, negativization of blood cultures, concentration of Streptococcus sanguis II in aortic vegetations, rate of sterilization of vegetations, body weight and serum bactericidal capacity. RESULTS: Vegetations weight was significantly lower in treated groups than in controls; lower weights were found in groups 2 and 4. The lowest vegetation weight was recorded in group 4, the only treatment that sterilized 75% of vegetations. Death occurred only in the control group (10%). Negativization of blood cultures was greatest and most rapid in group 4. Serum bactericidal capacity was greater after the two combined treatments, and highest in group 4. CONCLUSIONS: Combined treatment with vancomycin-gentamicin may be highly efficacious in patients with endocarditis caused by penicillin-resistant Streptococcus viridans.

Numerical analysis of fatty and mycolic acid profiles of Corynebacterium urealyticum and other related corynebacteria.

The fatty and mycolic acid profiles of 52 strains of clinical origin belonging to Corynebacterium urealyticum were subjected to numerical analysis along with those of representative members of Corynebacterium ammoniagenes, Corynebacterium bovis, Corynebacterium glutamicum, Corynebacterium jèikeium, Corynebacterium minutissimum, Corynebacterium pseudodiphtheriticum, Corynebacterium pseudotuberculosis, Corynebacterium xerosis, Corynebacterium renale, Corynebacterium cystitidis, "Corynebacterium ulcerans" and one strain of the Corynebacterium F1 group. Strains were divided into eight clusters at an amalgamation distance of 7.4. Corynebacterium urealyticum appeared as an homogeneous cluster clearly distant from others, that included several members of the genus Corynebacterium, and it was characterized by its content on unsaturated mycolic acids of mainly 28 (28:1) and 30 (30:3) carbon atoms. On the basis of these results the taxonomic "status" of Corynebacterium urealyticum, a new species within the genus Corynebacterium "sensu stricto", is further justified.

[Resistance in Haemophilus influenzae in Spain. 2d study (1990)]. / Resistencias en Haemophilus influenzae en España. Segundo estudio (1990).

AIM: To study the resistance to strains of H. influenzae simultaneously isolated during 1990 in 10 Spanish cities with this being the second multicentric study carried out in Spain. METHODS: Three hundred eight strains of H. influenzae were consecutively isolated with less than 50% being from the respiratory tract. The sensitivity by microdilution in supplement Isosensitest was studied. RESULTS: Thirty-five percent of the strains were producers of beta-lactamase which predominate among those isolated in systemic infections and specially among those from Madrid (58.78%) and Barcelona (61.8%). The strains producing beta-lactamase were more resistant to all the antimicrobials than the non producers. Five point two percent of the strains were resistant to ampicillin by non enzymatic mechanisms. Resistance to chloramphenicol is frequent (28.6%) especially among strains producing beta-lactamase, strains of ocular origin and ORL (46%) and systemic infections (74.3%). The distribution is irregular, being more frequent in Seville (66.7%) and not detectable in Barcelona. Resistance to tetracycline is also usually linked to the production of beta-lactamase and not necessarily to that of chloramphenicol. Resistance to cotrimoxazole is the most frequent (67.5%) specially in Valladolid (87.5%). Resistance to cefaclor is of 60.7% being the most frequent among those isolated from ocular processes and ORL. Only 28 strains (9.1%) were sensitive to all the antimicrobials tested. Thirty-nine percent were multiresistant. CONCLUSIONS: The authors found a slight increase in the high resistance detected in 1986. This increase was not uniform in all of Spain being significant in Madrid with producers of beta-lactamase, in Seville to chloramphenicol, to tetracycline in Bilbao and cotrimoxazole in Valencia.

Prophylaxis in transurethral surgery: oral lomefloxacin versus intravenous cefuroxime.

A randomized study compared the efficacy of a single dose of lomefloxacin given orally vs. cefuroxime given intravenously for prophylaxis against urinary tract infection in patients who were undergoing transurethral surgery. Patient groups were demographically similar; 25 received 400 mg lomefloxacin orally 2-6 h before surgery and 26 received 1.5 g cefuroxime intravenously 30-90 min before surgery. Urine cultures were obtained prior to surgery, 24 h after surgery and 3-5 days after surgery or before hospital discharge. Treatment was considered successful if bacterial culture showed < 10(5) CFU/ml. Clinical results expressed as success/failure rates showed success in 18 patients in the lomefloxacin group (72%) and 15 patients in the cefuroxime group (57.7%). Results demonstrated that lomefloxacin is superior to cefuroxime when used as prophylaxis against urinary tract infection following transurethral surgery. In addition, lomefloxacin may be preferable because of its convenient single-dose oral administration.

[Serodiagnosis in pulmonary tuberculosis. Clinical evaluation]. / Serodiagnóstico en la tuberculosis pulmonar. Valoración clínica.

The IgA, IgG, IgM and IgG subsets antibodies levels were determined in 200 patients with pulmonary tuberculosis and compared to three control groups: 80 healthy individuals (50 with negative PPD skin test, 30 with positive PPD skin test), 30 leprosy patients and 20 patients with different pulmonary diseases. The technique used was an enzyme linked assay. As antigens, purified tuberculin and Ag60 from M. bovis were used. There were not statistically significant differences between antibody levels among all control groups studied, but when we compare the level in control groups with that observed in tuberculous patients, they showed higher levels of IgA, IgG, IgM, IgG2 (p less than 0.01) and IgG4 (p less than 0.05). A definite diagnosis of tuberculosis of the lung should only be established if the patient showed to be positive to IgG plus IgA or IgM and in special cases to IgG1, reaching then a diagnostic efficacy of 90% in a patient population with a 68% of positive smears for acid-fast bacilli.

Comparison of the efficacy of three different treatments with imipenem versus the classical clindamycin plus tobramycin in experimental peritonitis.

This study compares the efficacy of three different treatment modalities of imipenem/cilastatin and the conventional clindamycin plus tobramycin in an experimental model of intra-abdominal sepsis. 145 Wistar rats were used. 40 served as control and 105 as study groups. A capsule with 0.5 ml of inoculum was surgically implanted in the peritoneal cavity. The inoculum was prepared from human feces of healthy volunteers, with a composition of E. coli 10(6), E. faecalis 10(6), B. fragilis, Clostridium sp 10(5) to 10(6) and anaerobic streptococci 10(5) to 10(6). Eighty animals were treated with imipenem/cilastatin and divided in 3 subgroups: "short pretreatment"--29 animals treated 1 hour prior to surgery and 3 days after; "short"--26 animals starting treatment 2 hours post-surgery and continuing it for 3 days; and "long"--25 animals treated for 10 days, starting 2 hours post-surgery. 25 animals received clindamycin plus tobramycin for 10 days. Mortality and the presence of visceral and peritoneal abscesses were the endpoints of the study. The control group had 100% mortality. There were no statistically significant differences among the treated groups although lower mortality was obtained with "short pretreatment" and "long" treatment with imipenem. The presence of abscesses were statistically significant between the imipenem and the combination group. In the imipenem groups, the "short pretreatment" and the long treatment had fewer abscesses than the short one. We conclude that imipenem may be a good alternative monotherapy to conventional therapy with clindamycin plus tobramycin. The "short pretreatment" seemed as good as the long one and better than the short treatment.

[Antimicrobial sensitivity of 402 strains of Neisseria gonorrhoeae isolated in 7 Spanish cities]. / Sensibilidad a antimicrobianos de 402 cepas de Neisseria gonorrhoeae aisladas en 7 ciudades de España.

To study N. gonorrhoeae resistance in Spain. We evaluate 402 strains consecutively isolated in 7 Spanish cities (Barcelona, Bilbao, Madrid, Murcia, Seville, Valencia and Valladolid). The MIC to 9 antimicrobial agents was determined by agar-dilution (DST) method. We found a high incidence (15.7%) of penicillinase producer strains (NGPP). Most (53.3%) of all non-NGPP strains showed reduced sensitivity to penicillin and 1.5% of the strains had chromosomally mediated resistance. All NGPP strains and 90% of non-NGPP strains showed reduced sensitivity to tetracycline (MIC greater than 0.23 mg/l). We did not found any strain with high-level tetracycline resistance. MIC90 for the other drugs tested were: erythromycin, 0.125 mg/l; spectinomycin, 16 mg/l; cefoxitin, 2 mg/l; cefuroxime 0.06 mg/l; ceftriaxone 0.0037 mg/l; ofloxacin 0.06 mg/l and ciprofloxacin, 0.0018 mg/l. NGPP are very prevalent in Spain. Most of these strains had chromosomally mediated resistance to penicillin and tetracycline. We did not found resistance to other antimicrobial agents.

[Cerebral abscess in a general hospital. Analysis of 66 consecutive cases]. / Los abscesos cerebrales en un hospital general. Análisis de 66 casos consecutivos.

BACKGROUND: Analysis of the epidemiologic characteristics of cerebral abscesses and comparison with 2 therapeutic schedules. METHODS: The clinical history of 66 patients with cerebral abscesses admitted over 14 years in the Neurosurgical Ward of the Virgen de la Arrixaca Hospital in Murcia were reviewed. Two therapeutic groups were designed of 33 and 31 patients respectively treated with classical or modern schedules and clinical efficacy was evaluated. RESULTS: Infections in the ORL area, craneoencephalic trauma, and brain surgery were the predisposing factors in 63% of the cases. The most frequent symptoms were migraine, fever, and alteration of consciousness in 75, 68 and 68% respectively. The most frequent locations were the temporal (36%), parietal (26%) and frontal lobes (23%). Microbiological studies were positive in 75% of the patients with the most frequent microorganisms being group A Streptococcus, Proteus mirabilis, Staphylococcus aureus and anaerobes. Mortality was 14%. Twenty-two percent of the patients had neurological sequelae. The rate of mortality was significantly associated to age greater than 40 years, fatal underlying disease, coma, initial clinical criteria and inadequate antibiotic treatment. The combination of cephotaxime-metronidazole was significantly associated to greater cure in comparison with the classical antibiotic combination although no significant differences were found in either the rate of mortality or relapse. CONCLUSIONS: The combination of cephotaxime-metronidazole may constitute an interesting advance in the treatment of these processes. The epidemiological data obtained confirm those of larger series.