Imma Grau

The effect of cephalosporin resistance on mortality in adult patients with nonmeningeal systemic pneumococcal infections

PURPOSE To evaluate the clinical relevance of cephalosporin (ceftriaxone/cefotaxime) resistance among patients with nonmeningeal systemic pneumococcal infection. SUBJECTS AND METHODS From January 1994 to October 2000, we prospectively studied 522 episodes of nonmeningeal systemic pneumococcal infections (448 pneumonias) in 499 adults who were treated according to hospital guidelines. In vitro antibiotic susceptibility, as the minimum inhibitory concentration (MIC), was determined by microdilution method. The MIC methods and breakpoints (cutoffs) were established by the National Committee for Clinical Laboratory Standards. RESULTS Of the 522 pneumococcal strains, 413 strains (79%) were susceptible to ceftriaxone/cefotaxime, MIC < or =0.5 microg/mL; 79 (15%) were intermediate, MIC = 1 microg/mL; and 30 (6%) were resistant, MIC = 2 microg/mL. After adjusting for several variables, including pneumococcal serogroups/serotypes, infections due to nonsusceptible (intermediate and resistant) pneumococcal strains were independently associated with prior antibiotic therapy, with an odds ratio of 5.9 (95% confidence interval: 2.6 to 13.6). Thirty-day mortality among the 185 patients who were treated with ceftriaxone (1 g/d) or cefotaxime (1.5 g every 8 hours) did not differ by cephalosporin susceptibility: 18% (26/148) among those with susceptible organisms, 13% (3/24) with intermediate organisms, and 15% (2/13) in resistant cases (P = 0.81). CONCLUSION Ceftriaxone or cefotaxime were effective in treating patients with nonmeningeal systemic pneumococcal infections caused by strains with MIC < or =2 microg/mL. These results support the newly established ceftriaxone/cefotaxime MIC breakpoints (cutoffs) for nonmeningeal pneumococcal infections.

Epidemiological and clinical characteristics of bacteraemia caused by Aeromonas spp. as compared with Escherichia coli and pseudomonas aeruginosa

We reviewed 75 episodes of Aeromonas spp. bacteraemia observed at our institution in 1979–2002, with special reference to episodes occurring in elderly patients (≥65 y) and to nosocomial episodes. In addition, we compared monomicrobial bacteraemic episodes caused by Aeromonas spp. (n=54) with those caused by Escherichia coli (n=108) and Pseudomonas aeruginosa (n=108), to assess differences in clinical presentation and outcome. The 75 episodes of Aeromonas spp. bacteraemia occurred mainly in males (72%), suffering from chronic liver disease (36%) or neoplasm (33%). They had an abdominal origin in 52% of cases, were recorded as primary bacteraemia in 40%, and showed a 30-d case fatality rate of 36%. 22 episodes (29%) were nosocomial, 36 (48%) occurred in elderly patients and 21 (28%) were polymicrobial infections. In comparison with Aeromonas spp., E. coli bacteraemia was more often associated with less severe underlying conditions, a community-acquired infection (74%), and a urinary tract (52%) or abdominal (27%) origin and had a 30-d case fatality rate of 24%. P. aeruginosa bacteraemia occurred mainly in patients with severe underlying conditions, was associated with nosocomial infection (69%), and had a 30-d case fatality rate of 43%. In conclusion, Aeromonas spp. bacteraemia is a serious infection that should be considered in patients with chronic liver disease or neoplasm. It may occur in the elderly and as a nosocomial infection, and differs in clinical findings from bacteraemia due to other common pathogens.

Invasive Pneumococcal Disease in Healthy Adults: Increase of Empyema Associated with the Clonal-Type Sweden1-ST306

Background Adult invasive pneumococcal disease (IPD) occurs mainly in the elderly and patients with co-morbidities. Little is known about the clinical characteristics, serotypes and genotypes causing IPD in healthy adults. Methods We studied 745 culture-proven cases of IPD in adult patients aged 18–64 years (1996–2010). Patients were included in two groups: 1.) adults with co-morbidities, and 2.) healthy adults, who had no prior or coincident diagnosis of a chronic or immunosuppressive underlying disease. Microbiological studies included pneumococcal serotyping and genotyping. Results Of 745 IPD episodes, 525 (70%) occurred in patients with co-morbidities and 220 (30%) in healthy adults. The healthy adults with IPD were often smokers (56%) or alcohol abusers (18%). As compared to patients with co-morbidities, the healthy adults had (P<0.05): younger age (43.5+/−13.1 vs. 48.7+/−11.3 years); higher proportions of women (45% vs. 24%), pneumonia with empyema (15% vs. 7%) and infection with non-PCV7 serotypes including serotypes 1 (25% vs. 5%), 7F (13% vs. 4%), and 5 (7% vs. 2%); and lower mortality (5% vs. 20%). Empyema was more frequently caused by serotype 1. No death occurred among 79 patients with serotype 1 IPD. There was an emergence of virulent clonal-types Sweden1-ST306 and Netherlands7F-ST191. The vaccine serotype coverage with the PCV13 was higher in healthy adults than in patients with co-morbidities: 82% and 56%, respectively, P<0.001. Conclusion In this clinical study, one-third of adults with IPD had no underlying chronic or immunosuppressive diseases (healthy adults). They were often smokers and alcohol abusers, and frequently presents with pneumonia and empyema caused by virulent clones of non-PCV7 serotypes such as the Sweden1-ST306. Thus, implementing tobacco and alcohol abuse-cessation measures and a proper pneumococcal vaccination, such as PCV13 policy, in active smokers and alcohol abusers may diminish the burden of IPD in adults.

Smoking and alcohol abuse are the most preventable risk factors for invasive pneumonia and other pneumococcal infections

OBJECTIVES To determine the prevalence of smoking and alcohol abuse among patients with invasive pneumococcal disease (IPD) in order to promote prevention strategies. METHODS We prospectively studied all culture-proven IPD cases in patients aged ≥ 18 years during the period 1997-2011. The habits of smoking and alcohol abuse were evaluated. Pneumococcal serotyping was performed. RESULTS There were 1378 IPD cases, with a mean age of 61 ± 17 years; 65% were males. Compared to the general population aged 18-64 years, patients with IPD of the same age group were more often current smokers (57% vs. 35%, p < 0.001) and alcohol abusers (21% vs. 6%, p < 0.001). Among patients with IPD, young adults (aged 18-49 vs. 50-64 vs. ≥ 65 years) were more commonly current smokers (71% vs. 40% vs.14%, p < 0.001) and alcohol abusers (23% vs. 18% vs. 6%, p < 0.001). Males were more frequently smokers and alcohol abusers than females. Smokers and alcohol abusers more often had underlying diseases such as HIV infection and chronic liver disease. Pneumonia was more common in smokers and peritonitis in alcohol abusers. Alcohol abuse conferred higher mortality. Certain pneumococcal serotypes, such as serotypes 1, 8, and 23F, more frequently caused IPD in smokers, and serotypes 4, 11A, and 19F in alcohol abusers. CONCLUSIONS Smoking and alcohol abuse are the most preventable risk factors for IPD. Implementing smoking and alcohol abuse cessation programs and a pneumococcal vaccination schedule are essential to diminish the burden of pneumonia and other pneumococcal infections.

Analysis of the discontinuation of protease inhibitor therapy in routine clinical practice

We evaluated the frequency of and reasons for discontinuation of protease inhibitor therapy in a cohort of HIV-infected patients in a prospective observational study. We included 230 HIV-infected patients who had started protease inhibitor therapy between November 1996 and July 1997. Mean baseline CD4 count was 138 cells/microl and HIV-RNA 4.5 log10. Forty-five percent of patients had prior AIDS and 77% had been treated with nucleoside analogues. Saquinavir-treated patients were at a less advanced stage of HIV disease. Overall, 41.3% of patients discontinued therapy, and their last HIV-RNA measured higher than that of patients who continued therapy: 4.07 vs. 2.70 log10 (p < 0.0001). Reasons for discontinuation of therapy were poor adherence (including abandonment) (18.6%), drug intolerance (12.1%), virological failure (7%) and physician decision (3.5%). In a multivariate model, factors associated with drug discontinuation were not taking indinavir (OR 0.26, 95% CI 0.12-0.59) and being pretreated with nucleoside analogues (OR 3.42, 95% CI 1.58-7.42). We concluded that in routine clinical practice a high proportion of patients discontinued protease inhibitors during the first 6 months of therapy, the main reason being the patients own decision (abandonment or poor adherence). Psychological support and counselling are warranted in patients when initiating protease inhibitor therapy.

An insidious nosocomial outbreak due to Salmonella enteritidis

OBJECTIVES To investigate an increase in the number of Salmonella enteritidis isolates detected in a large hospital to ascertain whether it was due to a nosocomial source, to identify the mechanisms of transmission, and to institute effective control measures to prevent future episodes. DESIGN Observational study, survey of all microbiological samples positive for S. enteritidis detected in the hospital, outbreak investigation, and review of the literature. SETTING A tertiary-care teaching hospital for adults in Barcelona, Spain. RESULTS During a 7-month period from May to November 1998, we identified 22 inpatients with S. enteritidis infection for whom nosocomial acquisition was strongly suspected. The attack rate was 0.138 per 1,000 patient-days. All affected patients were immunosuppressed and overall mortality was 41% (9 of 22). A sample of a meal cooked in the kitchen was culture positive for S. enteritidis. All isolates shared the same antibiotic susceptibility pattern and all except one shared the same pulsed-field gel electrophoresis (PFGE) pattern, but PFGE could not differentiate between outbreak-related and control strains. After compliance with kitchen hygiene procedures was emphasized and cleansing was intensified, no more cases were detected. CONCLUSIONS Apparently, sporadic cases of S. enteritidis may be part of an outbreak with a low attack rate. A small but persistent inoculum affecting only individuals with special predisposition for Salmonella infection might account for this. Suspicion should be raised in hospitals and institutions with a highly susceptible population.

The clinical epidemiology and malignancies associated with Streptococcus bovis biotypes in 506 cases of bloodstream infections

OBJECTIVES To determine the incidence of Streptococcus bovis (Sb) biotypes causing bacteraemia and associated malignancies. METHODS This is a retrospective analysis of patients with Sb bacteraemia, pulled out from a prospective surveillance protocol of bacteraemia cases, in three areas of Spain (1990-2013): a cattle area (Lugo), a fishing area (Ferrol) and an urban area (Barcelona). Colonoscopy and Sb biotypes (Sb-I and Sb-II) were determined in most cases. RESULTS 506 patients with Sb bacteraemia; mean age 68.1 (±14.1) years, and 66.2% were males. The cattle area, compared with the fishing and urban areas, had higher incidence of bacteraemia by SbI (40.29 vs 9.38 vs 6.15 cases/10(6) person-years, P < 0.001) and bacteraemia by Sb-II (29.07 vs 9.84 vs 13.37 cases/10(6) person-years, P < 0.001). The Sb-I cases (n = 224), compared with Sb-II cases (n = 270), had greater rates of endocarditis (77.6% vs 9.6%, P < 0.001) and colorectal neoplasm (CRN) (50.9% vs 16.6%, P < 0.001), and smaller rates of biliary tract infection (2.2% vs 29.6%, P < 0.001) and non-colorectal malignancy (8.9% vs 31.4%, P < 0.001). CONCLUSION There was a link between the cattle area and higher incidence of Sb bacteraemia. Sb-I differed from Sb-II cases in clinical findings and associated malignancies. Colonoscopy is mandatory in cases of endocarditis or bacteraemia caused by Sb-I.

Declining mortality from adult pneumococcal infections linked to children's vaccination

OBJECTIVE To determine changes in mortality among adults with invasive pneumococcal disease (IPD) after introducing pneumococcal conjugate vaccines (PCVs) in children. METHODS An active surveillance of adults with culture-proven IPD in Barcelona. Serotype-specific mortality and rates of disease and death were analysed in three periods: baseline (1994-2001), PCV7 (2002-2009) and PCV13 (2010-2013). RESULTS Overall, IPD caused by PCV7 serotypes was associated with increased case fatality rate (24 percent). In patients 18-64 years (baseline vs. PCV7 vs. PCV13 periods), case fatality rate from IPD decreased (22 vs.14 vs. 12 percent), and it was associated with a decline in PCV7 serotypes (3.56 vs. 2.80 vs. 1.49 cases/10(5) person-years) and in PCV7 serotypes-specific death (0.74 vs. 0.53 vs. 0.09 deaths/10(5) person-years). In patients ≥65 years, case fatality rate did not change (24 vs. 22 vs. 24 percent); however, there was a decline in PCV7 serotypes-specific death (4.94 vs. 3.58 vs. 2.45 deaths/10(5) person-years), and an increase in non-PCV serotypes-specific death (2.55 vs. 3.70 vs. 4.09 deaths/10(5) person-years). CONCLUSIONS The use of PCVs for children was associated with a reduction of mortality from IPD in adults 18-64 years, through the indirect effect of herd protection. In older adults, age-related factors could play a role in IPD mortality.

Clinical outcomes after combination treatment with ceftazidime/avibactam and aztreonam for NDM-1/OXA-48/CTX-M-15-producing Klebsiella pneumoniae infection

novel family of tetracycline-inactivating enzymes. Chem Biol 2015; 22: 888–97. 9 Bruin JP, Ijzerman EP, den Boer JW et al. Wild-type MIC distribution and epidemiological cut-off values in clinical Legionella pneumophila serogroup 1 isolates. Diagn Microbiol Infect Dis 2012; 72: 103–8. 10 EUCAST. Antimicrobial Susceptibility Testing of Legionella pneumophila. http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/General_doc uments/Legionella_guidance_document_20160909.pdf.

Colorectal neoplasm in cases of Clostridium septicum and Streptococcus gallolyticus subsp. gallolyticus bacteraemia

BACKGROUND Bacteremia with Clostridium septicum (CS) and Streptococcus gallolyticus subsp. gallolyticus (SGG) have both been associated with colorectal neoplasms (CRN) and colonoscopic examination is advised, however the differences and similarities in colorectal findings are not well known. METHODS This is a multicenter, comparative study of patients with CS bacteremia [44 of 664 cases (6.6%) of Clostridium spp.] and SGG bacteremia [257 of 596 cases (44.2%) of S. bovis group], carried out in three hospitals from Spain. Clinical findings related to bacteremia and associated CRN were collected. RESULTS The main sources of infection were abdominal (77.7%) for CS bacteremia and endovascular (75%) for SGG bacteremia. CS bacteremia was more often associated with malignancies, (72.6% vs. 19.4%) and neutropenia (29.5% vs. 3.1%), and was more acute, with shock at presentation (63.6% vs. 3.9%) and higher 30-day mortality (47.7% vs. 9.7%) compared to SGG (P<0.05 for all). Both, patients with CS and SGG bacteremia often had concomitant CRN (43.1% vs. 49.8%) and most of them presented as occult CRN (73.7% vs. 91.4%; P=0.02). CS cases more often had invasive carcinomas (94.7% vs. 19.5%), location of CRN in the right colon (73.7% vs. 23.4%), larger tumor size (median 7 vs. 1.5cm), and a higher overall CRN related mortality rate (68.4% vs. 7.8%) compared to SGG cases (P<0.05 for all). CONCLUSIONS Both, CS and SGG bacteremia are associated with occult CRN. CS cases more often had advanced carcinomas than SGG cases, suggesting a distinct temporal association with CRN.