M. T. Jiménez de Anta

Pathogenic significance of methicillin resistance for patients with Staphylococcus aureus bacteremia

To assess whether methicillin resistance is a microbial characteristic associated with deleterious clinical outcome, we performed a cohort study on 908 consecutive episodes of Staphylococcus aureus bacteremia and a case-control study involving 163 pairs of patients matched for preexisting comorbidities, prognosis of the underlying disease, length of hospitalization, and age. Of 908 bacteremic episodes, 225 (24.8%) were due to methicillin-resistant S. aureus (MRSA). Multivariate analysis did not reveal that methicillin resistance was an independent predictor for mortality when shock, source of bacteremia, presence of an ultimately or rapidly fatal underlying disease, acquisition of the infection in an intensive care unit (ICU), inappropriate empirical therapy, female sex, and age were taken into account. Nonetheless, methicillin resistance was an independent predictor for shock. The case-control study could not confirm that shock was linked to MRSA when prior antimicrobial therapy, inappropriate treatment, ICU residence, and female sex were considered. Our data suggest that cohort studies tend to magnify the relationship of MRSA with clinical markers of microbial pathogenicity and that this effect is a shortcoming of these kind of studies that is caused by inadequate control for underlying diseases.

Rapid urinary antigen test for diagnosis of pneumococcal community-acquired pneumonia in adults

Streptococcus pneumoniae is suspected to cause an important proportion of community-acquired pneumonia (CAP) whose aetiology cannot be detected with conventional tests. In this study, the authors evaluated the diagnostic yield of a new immunochromatographic membrane test (ICT) for the detection of the S. pneumoniae antigen in the urine of patients admitted with diagnosed CAP. ICT was performed in unconcentrated and concentrated urine from all the patients. ICT was repeated 1 month after discharge in a group initially testing positive. The authors also studied the ICT in clinically stable human immunodeficiency virus type 1 (HIV1)-infected patients. S. pneumoniae antigen was detected in all of the 68 (100%) patients tested with definitive pneumococcal pneumonia. In five of these cases ICT was only positive when it had been performed on the patients. The S. pneumoniae antigen was also detected in 36 (69.2%) of 52 patients with probable pneumococcal pneumonia and in 50 of 277 (18%) patients without pneumococcal pneumonia. ICT remained positive in 16 (69.5%) of 23 patients, 1 month after hospital discharge. Nasopharyngeal colonisation with S. pneumoniae was detected in 8 (12%) of 68 clinically stable HIV1 infected patients, but none tested ICT positive. The Binax NOW® immunochromatographic membrane test is a rapid, sensitive and specific test for detecting pneumococcal community-acquired pneumonia in adults. The test may remain positive for several weeks after pneumococcal pneumonia.

A comparative study of different PCR-based DNA fingerprinting techniques for typing of the Acinetobacter calcoaceticus-A. baumannii complex

Different PCR-based DNA fingerprinting techniques were evaluated for typing 26 clinical isolates belonging to the Acinetobacter calcoaceticus-A. baumannii complex. Seven isolates belonged to a previously defined outbreak while 19 isolates were unrelated epidemiologically. The PCR-based DNA fingerprinting techniques used were: (i) repetitive extragenic palindromic (REP) PCR; (ii) enterobacterial repetitive intergenic consensus (ERIC) PCR; (iii) randomly amplified polymorphic DNA with M13 forward primer; (iv) restriction analysis of the amplified 16S rRNA gene (ARDRA-16S); and (v) restriction analysis of an amplified region containing the 16S-23S rRNA spacer region and part of the 23S rRNA gene (ARDRA 23S + spacer). The discrimination index for the PCR-based DNA fingerprinting techniques was: 0.99 for REP; 0.94 for ERIC; 0.87 for M13; 0.60 for ARDRA-16S digested with Hpa II and <0.50 for ARDRA 23S + spacer. It was concluded that REP-PCR possessed high discriminatory power and reproducibility in comparison with the other PCR-based DNA fingerprinting techniques, and is a simple and rapid typing method for use in epidemiological studies of isolates belonging to the A. calcoaceticus-A. baumannii complex.

Quinolones Induce Partial or Total Loss of Pathogenicity Islands in Uropathogenic Escherichia coli by SOS-Dependent or -Independent Pathways, Respectively

ABSTRACT Escherichia coli is the most common microorganism causing urinary tract infections. Quinolone-resistant E. coli strains have fewer virulence factors than quinolone-susceptible strains. Several urovirulence genes are located in pathogenicity islands (PAIs). We investigated the capacity of quinolones to induce loss of virulence factors such as hemolysin, cytotoxic necrotizing factor 1, P fimbriae, and autotransporter Sat included in PAIs in three uropathogenic E. coli strains. In a multistep selection, all strains lost hemolytic capacity at between 1 and 4 passages when they were incubated with subinhibitory concentrations of ciprofloxacin, showing a partial or total loss of the PAI containing the hly (hemolysin) and cnf-1 (cytotoxic necrotizing factor 1) genes. RecA− mutants were obtained from the two E. coli strains with partial or total loss of the PAI. The inactivation of the RecA protein affected only the partial loss of the PAI induced by quinolones. No spontaneous loss of PAIs was observed on incubation in the absence of quinolones in either the wild-type or mutant E. coli strains. Quinolones induce partial or total loss of PAIs in vitro in uropathogenic E. coli by SOS-dependent or -independent pathways, respectively.

Enteroaggregative Escherichia coli Strains as a Cause of Traveler's Diarrhea: A Case-Control Study

To elucidate the importance of enteroaggregative Escherichia coli (EAggEC) strains as a cause of travelers diarrhea in Spanish travelers, a prospective case-control 1:1 study was done in a university hospital clinic for travelers. EAggEC strains were isolated from 23 of 165 case-patients and from 4 of 165 controls (P = .0003). In 16 patients, this was the only isolate recovered. Six of the EAggEC-positive isolates from the case-patients and 2 from the controls were positive for the enteroaggregative stable toxin type 1 gene. Other enteropathogens were also isolated. Shigella and enterotoxigenic E. coli strains showed significant differences between cases and controls (P = .0023 and P < .0001, respectively). Geographic distribution of the EAggEC strains was homogeneous, and the clinical symptom, secretory diarrhea, did not differ statistically with that for the enterotoxigenic E. coli strains. EAggEC strains are a cause of secretory diarrhea in Spaniards traveling to developing countries.

Daptomycin Is Effective for Treatment of Experimental Endocarditis Due to Methicillin-Resistant and Glycopeptide-Intermediate Staphylococcus epidermidis

ABSTRACT This study evaluated the daptomycin activity against two methicillin-resistant Staphylococcus epidermidis (MRSE) clinical isolates with different vancomycin susceptibilities: MRSE-375, with a vancomycin MIC of 2 μg/ml, and NRS6, a glycopeptide-intermediate S. epidermidis (GISE) strain with a vancomycin MIC of 8 μg/ml. The in vivo activity of daptomycin at two different doses (standard dose [SD-daptomycin], 6 mg/kg of body weight/day intravenously [i.v.]; high dose [HD-daptomycin], 10 mg/kg/day i.v.) was evaluated in a rabbit model of infective endocarditis and compared with that of a standard dose of vancomycin (SD-vancomycin; 1 g i.v. every 12 h) for 2 days. For the MRSE-375 strain, high-dose vancomycin (HD-vancomycin; 1 g i.v. every 6 h) was also studied. For MRSE-375, SD- and HD-daptomycin therapy sterilized significantly more vegetations than SD-vancomycin therapy (9/15 [60%] and 11/15 [73%] vegetations, respectively, versus 3/16 [19%] vegetations; P = 0.02 and P = 0.002, respectively). HD-daptomycin sterilized more vegetations than HD-vancomycin (11/15 [73%] versus 5/15 [33%] vegetations; P = 0.03) and was more effective than SD- and HD-vancomycin in reducing the density of bacteria in valve vegetations (0 log10 CFU/g vegetation [interquartile range {IQR}, 0 to 1 log10 CFU/g vegetation] versus 2 log10 CFU/g vegetation [IQR, 2 to 2 log10 CFU/g vegetation] and 2 log10 CFU/g vegetation [IQR, 0 to 2.8 log10 CFU/g vegetation]; P = 0.002 and P = 0.01, respectively). For the NRS6 strain, SD- and HD-daptomycin were significantly more effective than vancomycin in reducing the density of bacteria in valve vegetations (3.7 log10 CFU/g vegetation [IQR, 2 to 6 log10 CFU/g vegetation] versus 7.1 log10 CFU/g vegetation [IQR, 5.2 to 8.5 log10 CFU/g vegetation]; P = 0.02). In all treatment arms, isolates recovered from vegetations remained susceptible to daptomycin and vancomycin and had the same MICs. In conclusion, daptomycin at doses of 6 mg/kg/day or 10 mg/kg/day is more effective than vancomycin for the treatment of experimental endocarditis due to MRSE and GISE.

Trends in frequency and in vitro susceptibilities to antifungal agents, including voriconazole and anidulafungin, of Candida bloodstream isolates. results from a six-year study (1996–2001)

The frequency of isolation and antifungal susceptibility patterns to established and two new antifungal agents were determined for 218 Candida spp isolates causing bloodstream infection from 1996 to 2001. Overall, 41.7% of the candidemias were due to C. albicans, followed by C. parapsilosis (22%), C. tropicalis (16.1%), C. glabrata (11.9%), C. krusei (6%) and miscellaneous Candida spp (2.3%). Isolates of C. albicans C. parapsilosis and C. tropicalis (80% of isolates) were highly susceptible to fluconazole (94 to 100% at </= 8 microg/ml) and voriconazole (97 to 100% at </= 1 microg/ml). By comparison with the newer agents itraconazole was less active (77 to 97% at </=0.12 microg/ml). Only 77% and 15% of C. glabrata isolates were inhibited by fluconazole at </= 8 microg/ml and itraconazole at </=0.12 microg/ml, respectively. Voriconazole showed a remarkable in vitro potency against C. glabrata as well as C. krusei isolates (100% at </= 1 microg/ml). Anidulafungin was very active against Candida spp isolates (MIC90: </= 0.5 microg/ml), except C. parapsilosis (MIC90: 4 microg/ml) and two C. guilliermondii isolates (MIC: >/= 32 microg/ml).

Pseudomonas aeruginosa bacteremia in patients infected with human immunodeficiency virus type 1

Abstract A prospective analysis of 43 episodes of Pseudomonas aeruginosa bacteremia in HIV-1-infected subjects was performed and the results compared with the incidence and outcome of Pseudomonasaeruginosa bacteremia in other high-risk patients, such as transplant recipients, leukemia patients, or patients hospitalized in the intensive care unit. The incidence of bacteremia/fungemia as a whole and of gram-negative and Pseudomonasaeruginosa bacteremia in particular was greater in HIV-1-infected subjects than in the unselected general population admitted. In contrast, the incidence of Pseudomonasaeruginosa bacteremia in HIV-1-infected patients did not differ from that in patients with other high-risk conditions. In patients with HIV-1 infection, independent risk factors for presenting Pseudomonasaeruginosa bacteremia were nosocomial origin (OR, 2.7; 95% CI, 1.3–5.7), neutropenia (OR, 2.7; 95% CI, 1.07–6.8), previous treatment with cephalosporins (OR, 3.6; 95% CI, 1.1–11.6), and a CD4+ cell count lower than 50 cells/mm3 (OR, 3.1; 95% CI, 1.7–8.6). Primary bacteremia and pneumonia were the most common forms of presentation. Fourteen (33%) patients died as a consequence of the bacteremia. The presence of severe sepsis (OR, 17.5; 95% CI, 3.2–68) and the institution of inappropriate definitive antibiotic therapy (OR, 2.7; 95% CI, 1.1–13) were independently associated with a poor outcome. One year after the development of bacteremia, only eight (19%) patients remained alive.

Prevalence of hepatitis B markers in the population of catalonia (Spain). Rationale for universal vaccination of adolescents

The prevalence of hepatitis B markers was determined in a representative sample of the general population of Catalonia (Spain). HBsAg was found in 0.5% of children (less than 15 years of age) and in 1.7% of adults (more than 15 years of age), and anti HBs in 1.6% and 18%, respecitvely. Age-specific prevalence for both markers showed a low risk for hepatitis B before puberty, and a progressive rise since adolescence, suggesting that perinatal transmission and horizontal transmission in children are relatively uncommon in Spain. Prevalence of hepatitis B markers was significantly higher among subjects with low education level, residing in an urban area and born outside Catalonia, but in the stratified analysis, a statistical significant difference was only maintained in the prevalence of HBV markers between those who live in urban and rural areas, and between those who were born outside Catalonia and in Catalonia. These data may be used as a basis for a strategy of hepatitis B prevention in Spain which include universal vaccination of adolescents, passive-active immunization of newborns to HBsAg positive mothers and vaccination of susceptible adults subjects from high-risk groups.

Addition of Gentamicin or Rifampin Does Not Enhance the Effectiveness of Daptomycin in Treatment of Experimental Endocarditis Due to Methicillin-Resistant Staphylococcus aureus

ABSTRACT This study evaluated the activity of daptomycin combined with either gentamicin or rifampin against three methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates in vitro and one isolate in vivo against a representative strain (MRSA-572). Time-kill experiments showed that daptomycin was bactericidal against these strains at concentrations over the MIC. Daptomycin at sub-MIC concentrations plus gentamicin at 1× and 2× the MIC yielded synergy, while the addition of rifampin at 2 to 4 μg/ml resulted in indifference (two strains) or antagonism (one strain). The in vivo activity of daptomycin (6 mg/kg of body weight once a day) was evaluated ± gentamicin (1 mg/kg intravenously [i.v.] every 8 h [q8h]) or rifampin (300 mg i.v. q8h) in a rabbit model of infective endocarditis by simulating human pharmacokinetics. Daptomycin plus gentamicin (median, 0 [interquartile range, 0 to 2] log10 CFU/g vegetation) was as effective as daptomycin alone (0 [0 to 2] log10 CFU/g vegetation) in reducing the density of bacteria in valve vegetations (P = 0.83), and both were more effective than daptomycin plus rifampin (3 [2 to 3.5] log10 CFU/g vegetation; P < 0.05) for the strain studied. In addition, daptomycin sterilized a ratio of vegetations that was similar to that of daptomycin plus gentamicin (10/15 [67%] versus 9/15 [60%]; P = 0.7), and both regimens did so more than daptomycin plus rifampin (3/15 [20%]; P = 0.01 and P = 0.02, respectively). No statistical difference was noted between daptomycin plus gentamicin and daptomycin alone for MRSA treatment. In the combination arm, all isolates from vegetations remained susceptible to daptomycin, gentamicin, and rifampin. Sixty-one percent of the isolates (8/13) acquired resistance to rifampin during monotherapy. In the daptomycin arm, resistance was detected in only one case, in which the daptomycin MIC rose to 2 μg/ml among the recovered bacteria. In conclusion, the addition of gentamicin or rifampin does not enhance the effectiveness of daptomycin in the treatment of experimental endocarditis due to MRSA.