Jose Antonio Martinez

Analysis of 4758 Escherichia coli bacteraemia episodes: predictive factors for isolation of an antibiotic-resistant strain and their impact on the outcome.

OBJECTIVES To describe the predictive factors for the isolation of fluoroquinolone-resistant or extended- spectrum beta-lactamase (ESBL)-producing Escherichia coli and their impact on bacteraemia outcome. METHODS Analysis of E. coli bacteraemia episodes prospectively collected through a blood culture surveillance programme from January 1991 to December 2007. RESULTS Out of 18 080 episodes, 4758 (26%) E. coli bacteraemias were reported in the period of study. Mortality was noted in 440 cases (9%). Fluoroquinolone-resistant strains were reported in 1300 (27%) cases and ESBL-producing strains in 211 cases (4%). One hundred and seventy-eight strains out of 211 (84%) ESBL-producing E. coli were isolated since 2001. The two main independent risk factors for mortality were shock (OR: 10.28, P < 0.001) and inappropriate empirical therapy (OR: 4.83, P < 0.001). Inappropriate empirical therapy was significantly more frequent for infections caused by fluoroquinolone-resistant strains (n = 203, 16%, P < 0.001) and ESBL-producing strains (n = 110, 52%, P < 0.001). Independent factors associated with the isolation of a fluoroquinolone-resistant strain were: nosocomial origin (OR: 1.61, P < 0.001); urinary catheterization (OR: 2.44, P < 0.001); and previous therapy with a fluoroquinolone (OR: 7.41, P < 0.001). The independent risk factors associated with the isolation of an ESBL-producing strain were: nosocomial origin (OR: 1.68, P = 0.03); urinary catheterization (OR: 1.88, P = 0.001); and previous beta-lactam antibiotic therapy (OR: 2.81, P < 0.001). CONCLUSIONS Inappropriate empirical therapy was the strongest independent factor that we could modify to improve mortality in E. coli bacteraemia and was more frequent in cases caused by fluoroquinolone-resistant or ESBL-producing strains. Nosocomial acquisition, urinary catheterization and previous therapy with a fluoroquinolone or beta-lactam were predictive factors for infection with an antibiotic-resistant strain.

Differences in virulence factors among clinical isolates of Escherichia coli causing cystitis and pyelonephritis in women and prostatitis in men.

ABSTRACT Differences in the presence of nine urovirulence factors among clinical isolates of Escherichia coli causing cystitis and pyelonephritis in women and prostatitis in men have been studied. Hemolysin and necrotizing factor type 1 occur significantly more frequently among isolates causing prostatitis than among those causing cystitis (P < 0.0001) or pyelonephritis (P < 0.005). Moreover, the papGIII gene occurred more frequently in E. coli isolates associated with prostatitis (27%) than in those associated with pyelonephritis (9%) (P < 0.05). Genes encoding aerobactin and PapC occurred significantly less frequently in isolates causing cystitis than in those causing prostatitis (P < 0.01 and P < 0.0001, respectively) and pyelonephritis (P < 0.01 and P < 0.0001, respectively). No differences in the presence of Sat or type 1 fimbriae were found. Finally, AAFII and Bfp fimbriae are no longer considered uropathogenic virulence factors since they were not found in any of the strains analyzed. Overall, the results showed that clinical isolates producing prostatitis need greater virulence than isolates producing pyelonephritis in women or, in particular, cystitis in women (P < 0.05). Overall, the results suggest that clinical isolates producing prostatitis are more virulent that those producing pyelonephritis or cystitis in women.

Candida species bloodstream infection: epidemiology and outcome in a single institution from 1991 to 2008.

Candidaemia remains a major cause of morbidity and mortality in the healthcare setting. Candida spp. bloodstream infection episodes prospectively recorded through a blood culture surveillance programme in a single institution from 1991 to 2008 were included in the study. Data regarding candidaemia episodes were analysed, including specific fungal species and patient survival at 30 days after diagnosis. There were 529 candidaemia episodes during the study period (495 were nosocomial infections). The incidence of candidaemia caused by non-Candida albicans Candida spp. (52%) was higher than the incidence of candidaemia caused by C. albicans (48%). The overall crude 30 day mortality rate was 32%. Patients with Candida parapsilosis candidaemia had the lowest mortality rate (23%). Candida krusei candidaemia was most commonly associated with haematological malignancy (61%; P < 0.001), stem cell transplantation (22%; P = 0.004), neutropenia (57%; P = 0.001) and prior use of antifungal azole agents (26%; P < 0.001). Patients with C. krusei candidaemia had the highest crude 30 day mortality in this series (39%). Epidemiological studies are important to define clinical and microbiological candidaemia characteristics and to guide empirical treatment in every setting.

Reversible Inhibition of Mitochondrial Protein Synthesis during Linezolid-Related Hyperlactatemia

ABSTRACT The objective of the present study was to determine the mitochondrial toxicity mechanisms of linezolid-related hyperlactatemia. Five patients on a long-term schedule of linezolid treatment were studied during the acute phase of hyperlactatemia and after clinical recovery and lactate normalization following linezolid withdrawal. Mitochondrial studies were performed with peripheral blood mononuclear cells and consisted of measurement of mitochondrial mass, mitochondrial protein synthesis homeostasis (cytochrome c oxidase [COX] activity, COX-II subunit expression, COX-II mRNA abundance, and mitochondrial DNA [mtDNA] content), and overall mitochondrial function (mitochondrial membrane potential and intact-cell oxidative capacity). During linezolid-induced hyperlactatemia, we found extremely reduced protein expression (16% of the remaining content compared to control values [100%], P < 0.001) for the mitochondrially coded, transcribed, and translated COX-II subunit. Accordingly, COX activity was also found to be decreased (51% of the remaining activity, P < 0.05). These reductions were observed despite the numbers of COX-II mitochondrial RNA transcripts being abnormally increased (297%, P = 0.10 [not significant]) and the mitochondrial DNA content remaining stable. These abnormalities persisted even after the correction for mitochondrial mass, which was mildly decreased during the hyperlactatemic phase. Most of the mitochondrial abnormalities returned to control ranges after linezolid withdrawal, lactate normalization, and clinical recovery. Linezolid inhibits mitochondrial protein synthesis, leading to decreased mitochondrial enzymatic activity, which causes linezolid-related hyperlactatemia, which resolves upon discontinuation of linezolid treatment.

Decreased Invasive Capacity of Quinolone-Resistant Escherichia coli in Patients with Urinary Tract Infections

Quinolone-resistant (QR) Escherichia coli may have lower invasive capacity than does quinolone-susceptible E. coli. To evaluate this, we prospectively collected data regarding all cases of E. coli invasive urinary tract infections (IUTI) in 669 adults admitted to the Infectious Diseases Unit of our hospital during a 3-year period, as well as 10,950 patients with cystitis or asymptomatic bacteriuria who presented to the outpatient clinic during a 1-year period. QR E. coli was isolated in 20% of patients with cystitis, compared with 8% of those with IUTI (P<.05). The proportion of E. coli isolates that were quinolone resistant was similar in patients with bacteremic and nonbacteremic IUTI. The factors of urinary manipulation and structural abnormalities were independently associated with the presence of quinolone resistance. Old age was the only variable independently associated with blood invasion. QR E. coli is less likely to produce invasive disease (pyelonephritis and prostatitis) than is quinolone-susceptible E. coli. However, once pyelonephritis or prostatitis have developed, there is no difference in the incidence of bacteremia.

Clinical utility of blood cultures drawn from central venous or arterial catheters in critically ill surgical patients.

Objective To determine the sensitivity, specificity, and predictive values of cultures done with blood drawn through a central venous or arterial catheter compared with peripheral venipuncture. Design Retrospective cohort study of critically ill surgical patients in whom samples for paired cultures were drawn through a central venous or arterial catheter and peripheral venipuncture. Setting Tertiary-care, university-affiliated medical center. Patients Two hundred seventy-one patients hospitalized on a surgical and a cardiothoracic intensive care unit between November 1994 and August 1997. Interventions None. Measurements and Main Results Blinded assessments of culture results done by two physicians were used as the gold standard. Sensitivity, specificity, and positive and negative predictive values were compared for culture of blood from catheters and culture of blood from peripheral venipuncture. Of 499 observations, 426 were catheter-negative/venipuncture-negative, 19 were catheter-positive/venipuncture-positive, 18 were catheter-negative/venipuncture-positive, and 36 were catheter-positive/venipuncture-negative pairs. For catheter draws compared with peripheral venipuncture, sensitivity was 78% (confidence interval [CI], 65% to 90%) and 65% (CI, 50% to 79%) (p = .2), specificity was 95% (CI, 94% to 97%) and 98% (CI, 97% to 99%) (p = .002), positive predictive value was 63% (CI, 51% to 76%) and 78% (CI, 64% to 91%) (p = .1) and negative predictive value was 98% (CI, 96% to 99%) and 97% (CI, 95% to 98%) (p = .3). When central venous specimens as differentiated from arterial catheter specimens were compared with peripheral venipuncture, the difference between positive predictive values reached statistical significance (61% and 82%;p = .04). Conclusions In critically ill surgical patients, cultures of blood drawn through a catheter are less specific than those obtained from a peripheral venipuncture. Both types of cultures have an excellent negative predictive value. Positive predictive value of cultures of blood drawn through a catheter is low and, when obtained from a central line, statistically less than from a peripheral venipuncture. Additional cultures seem to be necessary for the proper interpretation of a positive culture drawn through a catheter in critical care patients.

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.

Tuberculosis transmission patterns among Spanish‐born and foreign‐born populations in the city of Barcelona

During a 2-year period (2003-2004), tuberculosis (TB) transmission in Barcelona and the factors related to transmission among the Spanish- and foreign-born populations were studied by molecular epidemiology. Data were obtained from TB cases and Conventional Contact Tracing registries and genotyping was performed using restriction fragment length polymorphism (RFLP)-IS6110 and MIRU12 as a secondary typing method. Of the 892 TB cases reported, 583 (65.3%) corresponded to Spanish-born and 309 (34.6%) to foreign-born. Six hundred and eighty-seven cases (77%) were confirmed by culture. RFLP typing of 463/687 (67.4%) isolates was performed, revealing 280 (60.5%) unique and 183 (39.5%) shared patterns, which were grouped into 65 clusters. Spanish-born individuals were significantly more clustered than foreign-born individuals (44.6% vs. 28.8%; p 0.016). Clustering in foreign-born individuals was associated with HIV (p 0.051, odds ratio = 3.1, 95% confidence interval 1-10.9) and alcohol abuse (p 0.022), whereas, in the Spanish-born individuals, clustering was associated with age in the range 21-50 years, (p 0.024). Of the total clusters, 36/65 (55.3%) included only Spanish-born patients, whereas 22/65 (33.8%) included individuals from both populations. In mixed clusters, the index case was Spanish-born in 53% and foreign-born in 47%. Among the foreign-born, 2.8% were ill on arrival, 30% developed TB within the first year and 50.3% developed TB within the first 2 years; 58.3% were from South America. In conclusion, half of the foreign-born TB patients developed the disease during the first 2 years after arrival, which, in most cases, was the result of endogenous reactivation. Recent TB transmission among Spanish-born and foreign-born populations, as well as bidirectional transmission between communities, contributed significantly to the burden of TB in Barcelona, suggesting the need to improve Public Health interventions in both populations.

Expression of Interleukin-8 Receptors (CXCR1 and CXCR2) in Premenopausal Women with Recurrent Urinary Tract Infections

ABSTRACT The migration of neutrophils through infected tissues is mediated by the CXC chemokines and its receptors (CXCR1 and CXCR2). It has been proposed that a CXCR1 deficiency could confer susceptibility to acute pyelonephritis in children. The objective of the study is to assess the surface expression of CXCR1 and CXCR2 and the existence of polymorphisms in the CXCR1 gene in premenopausal women with recurrent urinary tract infections. The study included 20 premenopausal women with recurrent urinary infections, with normal urinary tracts, and without diseases potentially associated with relapsing urinary infections and 30 controls without previous urinary infections. The levels of CXCR1 and CXCR2 expression on neutrophils were measured and analyzed by flow cytometry by measuring the mean fluorescence intensity (MFI) channel. The promoter and coding regions of the CXCR1 gene were analyzed for the presence of polymorphisms by a sequence-based typing method. Patients with recurrent urinary tract infections exhibited median levels of CXCR1 expression, determined from MFI values, similar to those of the controls. The analysis of CXCR2 showed that patients with recurrent urinary infections had lower median levels of expression, determined from the MFI values, than the controls (P = 0.002, Mann-Whitney U test). No polymorphisms were detected at the promoter or at the exon 1 region of the CXCR1 gene either in the patients or in the controls. Polymorphisms were detected at the exon 2 of CXCR1, but their frequencies did not differ between patients and controls. We have found a low level of CXCR2 expression in patients with recurrent urinary tract infections. These results suggest that a low level of CXCR2 expression may increase the susceptibilities of premenopausal women to urinary tract infections.