Epidemiological and clinical characteristics of Streptococcus tigurinus endocarditis.

BACKGROUND: Streptococcus tigurinus was recently described as a new streptococcal species within the viridans group streptococci (VGS). The objectives of the present work were to analyse the clinical and microbiological characteristics of S. tigurinus isolated from patients with bacteraemias, to determine the prevalence of S. tigurinus among VGS endocarditis in Spain, and to compare the clinical characteristics and outcomes of endocarditis caused by S. tigurinus and other VGS. METHODS: Retrospective nationwide study, performed between 2008 and 2016 in 9 Spanish hospitals from 7 different provinces comprising 237 cases of infective endocarditis. Streptococcal isolates were identified by sequencing fragments of their 16S rRNA, sodA and groEL genes. Clinical data of patients with streptococcal endocarditis were prospectively collected according to a pre-established protocol. RESULTS: Patients with endocarditis represented 7/9 (77.8%) and 26/86 (30.2%) of the bacteraemias caused by S. tigurinus and other VGS, respectively (p < 0.001), in two of the hospital participants. Among patients with streptococcal endocarditis, 12 different Streptococcus species were recognized being S. oralis, S. tigurinus and S. mitis the three more common. No relevant statistical differences were observed in the clinical characteristics and outcomes of endocarditis caused by the different VGS species. CONCLUSIONS: In this multicenter study performed in Spain, S. tigurinus showed a higher predilection for the endocardial endothelium as compared to other VGS. However, clinical characteristics and outcomes of endocarditis caused by S. tigurinus did not significantly differ from endocarditis caused by other oral streptococci.

Antimicrobial management of Tropheryma whipplei endocarditis: the Spanish Collaboration on Endocarditis (GAMES) experience.

OBJECTIVES: Tropheryma whipplei has been detected in 3.5% of the blood culture-negative cases of endocarditis in Spain. Experience in the management of T. whipplei endocarditis is limited. Here we report the long-term outcome of the treatment of previously reported patients who were diagnosed with infective endocarditis (IE) caused by T. whipplei from the Spanish Collaboration on Endocarditis-Grupo de Apoyo al Manejo de la Endocarditis Infecciosa en España (GAMES) and discuss potential options for antimicrobial therapy for IE caused by T. whipplei. PATIENTS AND METHODS: Seventeen patients with T. whipplei endocarditis were recruited between 2008 and 2014 in 25 Spanish hospitals. Patients were classified according to the therapeutic regimen: ceftriaxone and trimethoprim/sulfamethoxazole, doxycycline + hydroxychloroquine and other treatment options. RESULTS: Follow-up data were obtained from 14 patients. The median follow-up was 46.5 months. All patients completed the antibiotic treatment prescribed, with a median duration of 13 months. Six patients were treated with ceftriaxone and trimethoprim/sulfamethoxazole (median duration 13 months), four with doxycycline + hydroxychloroquine (median duration 13.8 months) and four with other treatment options (median duration 22.3 months). The follow-up after the end of the treatments was between 5 and 84 months (median 24 months). CONCLUSIONS: All treatment lines were effective and well tolerated. Therapeutic failures were not detected during the treatment. None of the patients died or experienced a relapse during the follow-up. Only six patients received antibiotic treatment in accordance with guidelines. These data suggest that shorter antimicrobial treatments could be effective.

Twenty-year experience with cryopreserved arterial allografts for vascular infections.

OBJECTIVES: The aim of this study was to analyse outcomes over 2 decades using cryopreserved vascular allografts to treat vascular infection. METHODS: We conducted a retrospective study of patients identified from our institutional database who were treated for primary or secondary vascular infection using implanted allografts. RESULTS: Between October 1992 and May 2014, 54 patients underwent surgery for vascular infection out of 118 patients implanted with cryopreserved vascular allografts. The 52 patients for whom we had full information form the basis of the study with a 96% follow-up. The average age was 64 ± 11 years; 87% were men; 65% had previous vascular surgery; 19% had emergency operations. A total of 75% of the patients had aortoiliofemoral infections. Five patients underwent surgery with cardiopulmonary bypass. Fifty percent required more than 1 allograft and 15% had concomitant procedures. Seventy-three percent (38/52) of specimen cultures yielded positive results with polymicrobial flora in 29%. Surgical specimens most frequently grew coagulase-negative staphylococci. The early postoperative reoperation rate was 15% for allograft-related complications. There were 20 (38%) early deaths, including deaths of acute myocardial infarction, anastomosis rupture and persistent sepsis and shock. Uncontrolled infection leading to septic shock and multiple organ failure was the cause of death in 50% of the cases. The mean duration of freedom from allograft reintervention was 12.2 years. The mean duration of freedom from allograft occlusion or limb loss was 12.1 years [95% confidence interval (CI) 9.9-14.4]. Of the 32 surviving patients, we had patency information for 66% obtained by angiography or computed tomography. The mean survival for the cohort was 5.9 years (95% CI 3.9-7.8). Mean freedom from cardiovascular infection-related death was 9.3 years (95% CI 7.2-11.4). CONCLUSIONS: Allografts can be indicated for treatment of primary/secondary infection and have remarkable results in multimorbid patients. Patients with vascular infection have a high-risk profile, around 40% mortality during the first 6 months, with reduction in overall mortality thereafter. We believe that allografts may play a role in the surgical treatment of vascular infection.

Development and validation of the INCREMENT-ESBL predictive score for mortality in patients with bloodstream infections due to extended-spectrum-ß-lactamase-producing Enterobacteriaceae.

Background: Bloodstream infections (BSIs) due to ESBL-producing Enterobacteriaceae (ESBL-E) are frequent yet outcome prediction rules for clinical use have not been developed. The objective was to define and validate a predictive risk score for 30 day mortality. Methods: A multinational retrospective cohort study including consecutive episodes of BSI due to ESBL-E was performed; cases were randomly assigned to a derivation cohort (DC) or a validation cohort (VC). The main outcome variable was all-cause 30 day mortality. A predictive score was developed using logistic regression coefficients for the DC, then tested in the VC. Results: The DC and VC included 622 and 328 episodes, respectively. The final multivariate logistic regression model for mortality in the DC included age >50 years (OR = 2.63; 95% CI: 1.18-5.85; 3 points), infection due to Klebsiella spp. (OR = 2.08; 95% CI: 1.21-3.58; 2 points), source other than urinary tract (OR = 3.6; 95% CI: 2.02-6.44; 3 points), fatal underlying disease (OR = 3.91; 95% CI: 2.24-6.80; 4 points), Pitt score >3 (OR = 3.04; 95 CI: 1.69-5.47; 3 points), severe sepsis or septic shock at presentation (OR = 4.8; 95% CI: 2.72-8.46; 4 points) and inappropriate early targeted therapy (OR = 2.47; 95% CI: 1.58-4.63; 2 points). The score showed an area under the receiver operating curve (AUROC) of 0.85 in the DC and 0.82 in the VC. Mortality rates for patients with scores of < 11 and ≥11 were 5.6% and 45.9%, respectively, in the DC, and 5.4% and 34.8% in the VC. Conclusions: We developed and validated an easy-to-collect predictive scoring model for all-cause 30 day mortality useful for identifying patients at high and low risk of mortality.

Enteric fever in Barcelona: Changing patterns of importation and antibiotic resistance.

BACKGROUND: Enteric fever's incidence is decreasing among residents of high-income countries, although it's rising in travelers coming from low-resource endemic settings. The study's aim is to describe epidemiological, clinical and laboratory features of patients with enteric fever. METHODS: Retrospective descriptive study of enteric fever cases diagnosed at a Tropical Medicine Unit in Barcelona, 1993-2012. RESULTS: Out of 40 patients, 31(77,5%) were returning travelers, and 70% of them had been in Southern Asia. In the rest of patients without an antecedent of a recent travel, the infection occurred mainly before year 2000. The more frequently reported symptoms were fever and diarrhea, lacking significant differences between S. typhi and S. paratyphi infections. Quinolones were used as empiric treatment in 47.2% of patients, 36.1% received 3rd generation cephalosporins, 2.78% azithromycin and 13.89% other combinations. Resistance to quinolones in the S. paratyphi group (66.7%) was significantly higher compared with the S. typhi group (20%) (p:0.02). 22.5% of patients had treatment failure and 23.6% patients presented complications, none of them had been previously vaccinated. CONCLUSIONS: The diagnosis of enteric fever was more frequent among travelers coming from Southern-East Asia. Quinolone resistance is widely spread, particularly in S. paratyphi serotypes and should not be considered as first choice treatment anymore.

Tropheryma whipplei endocarditis in Spain: Case reports of 17 prospective cases.

Tropheryma whipplei endocarditis is an uncommon condition with very few series and <90 cases reported in the literature. The aim of the study was to analyze the epidemiological, clinical, and outcome characteristics of 17 cases of T. whipplei endocarditis recruited in our country from a multicentric cohort from 25 Spanish hospitals from the Spanish Collaboration on Endocarditis-Grupo de Apoyo al Manejo de la Endocarditis infecciosa en España.From a total of 3165 cases included in the cohort, 14.2% were diagnosed of blood culture negative endocarditis (BCNE) and 3.5% of these had T. whipplei endocarditis. This condition was more frequent in men. The average age was 60.3 years. Previous cardiac condition was present in 35.3% of the cases. The main clinical manifestation was cardiac failure (76.5%) while fever was only present in the 35.3%. Ecocardiography showed vegetations in 64.7% of patients. Surgery was performed in all but 1 cases and it allowed the diagnosis when molecular assays were performed. A broad range rRNA 16S polymerase chain reaction was used for first instance in all laboratories and different specific targets for T. whipplei were employed for confirmation. A concomitant Whipple disease was diagnosed in 11.9% of patients. All patients received specific antimicrobial treatment for at least 1 year, with no relapse and complete recovery.T. whipplei endocarditis is an uncommon condition with an atypical presentation that must be considered in the diagnosis of BCNE. The prognosis is very good when an appropriate surgical management and antimicrobial-specific treatment is given.

Impact of the MIC of piperacillin/tazobactam on the outcome for patients with bacteraemia due to Enterobacteriaceae: the Bacteraemia-MIC project.

OBJECTIVE: Our objective was to evaluate the impact of low versus borderline MIC of piperacillin/tazobactam on the clinical outcomes of patients with bacteraemia caused by Enterobacteriaceae who were treated with that antimicrobial. PATIENTS AND METHODS: A prospective observational multicentre cohort study was conducted in 13 Spanish university hospitals. Patients >17 years old with bacteraemia due to Enterobacteriaceae who received empirical piperacillin/tazobactam treatment for at least 48 h were included. Outcome variables were clinical response at day 21, clinical response at end of treatment with piperacillin/tazobactam and all-cause 30 day mortality. Univariate and multivariate logistic regression analyses were performed. RESULTS: Overall, 275 patients were included in the analysis; 248 (90.2%) in the low MIC group (≤ 4 mg/L) and 27 (9.8%) in the borderline MIC group (8-16 mg/L). The biliary tract was the most common source of infection (48.4%) and Escherichia coli was the most frequent pathogen (63.3%). Crude 30 day mortality rates were 10.5% and 11.1% for the low MIC group and the borderline MIC group, respectively (relative risk = 1.06, 95% CI = 0.34-3.27, P = 1). Multivariate analysis of failure at day 21 and at end of treatment with piperacillin/tazobactam and 30 day mortality showed no trend towards increased clinical failure or mortality with borderline MICs (OR = 0.96, 95% CI = 0.18-4.88, P = 0.96; OR = 0.47, 95% CI = 0.10-2.26, P = 0.35; OR = 1.48, 95% CI = 0.33-6.68, P = 0.6). CONCLUSIONS: We did not find that higher piperacillin/tazobactam MIC within the susceptible or intermediate susceptibility range had a significant influence on the outcome for patients with bacteraemia due to Enterobacteriaceae.

Candida tropicalis bloodstream infection: Incidence, risk factors and outcome in a population-based surveillance.

OBJECTIVE: To assess the current clinical features and determinants of outcome of Candida tropicalis bloodstream infection (BSI). METHODS: A population-based surveillance on Candida BSI was conducted from May 2010 to April 2011 in 29 Spanish hospitals. Antifungal susceptibility testing (EUCAST methodology) was centrally performed. The characteristics and outcome of C. tropicalis BSI episodes were compared with those due to other species. RESULTS: Fifty-nine out of 752 episodes (7.8%) were due to C. tropicalis (annual incidence: 0.62 cases per 100,000 population). Resistance to fluconazole and voriconazole was found in 23.2% and 26.8% of isolates. Breakthrough BSI occurred in 10.5% of episodes. Risk factors for C. tropicalis BSI were age (odds ratio [OR]: 1.01; P-value = 0.05), underlying leukaemia (OR: 4.77; P-value = 0.001) and chronic lung disease (OR: 2.62; P-value = 0.002). There were no differences in clinical failure (persistent BSI for ≥72 h after initiation of therapy and/or 30-day all-cause mortality) between C. tropicalis (39.6%) and non-C. tropicalis groups (45.6%). The appropriateness of antifungal therapy or the fluconazole MIC values had no significant impact on outcome, whereas early central venous catheter removal exerted a protective effect. CONCLUSIONS: C. tropicalis BSI was associated with advanced age, haematological malignancy and respiratory comorbidity. We found no correlation between the unexpectedly high resistance rate to azoles observed and outcome.

Candida norvegensis fungemia in a liver transplant recipient.

BACKGROUND: The incidence of candidemia due to non-Candida albicans Candida species has been progressively increasing in recent years. The use of fluconazole as antifungal prophylaxis has been described as a risk factor for the development of infections by fluconazole resistant Candida strains. We report a case of Candida norvegensis bloodstream infection in a liver transplant recipient. CASE REPORT: A 61-year-old man, who received a third liver allograft and became worse with the onset of ischemic cholangiopathy and recurrent episodes of cholangitis, was admitted to our hospital due to the development of intra-abdominal abscesses. He received multiple antibiotic schemes, and after 3 months he was discharged, maintaining parenteral antibiotic at home. While he was on fluconazole prophylaxis, a breakthrough candidemia due to C. norvegensis occurred. In vitro susceptibilities of the isolate to several antifungal agents were as follows: amphotericin B MIC 0.5 mg/l, flucytosine 64 mg/l, fluconazole 64 mg/l, itraconazole 4 mg/l, voriconazole 0.75 mg/l, and caspofungin 0.047 mg/l. He was treated with anidulafungin with resolution of candidemia. CONCLUSIONS: The use of fluconazole for antifungal prophylaxis may lead to the emergence of fluconazole-resistant Candida infections, with C. norvegensis being a possible emerging pathogen in organ transplant recipients.

Plasma resistin levels are associated with homocysteine, endothelial activation, and nitrosative stress in obese youths.

OBJECTIVE: To evaluate whether serum resistin levels are related to cardiovascular risk in obese children. DESIGN AND METHODS: Cross-sectional study of 110 children (40 normal weight and 70 severely obese). Clinical and biochemical parameters, including lipid profile, fasting glucose and insulin, and homocysteine, were determined. The levels of adipokines (adiponectin, leptin, and resistin), markers of inflammation (high-sensitivity C-reactive protein (hs-CRP)), endothelial activation (serum concentrations of soluble intercellular and vascular cellular adhesion molecule-1 (sICAM-1, sVCAM-1)), and oxidative/nitrosative stress (malondialdehyde and urinary nitrate/nitrite) were measured. RESULTS: A partial correlation adjusted by gender, Tanner stage, and body mass index in obese children showed that resistin was significantly related to central obesity (p<0.002), insulin resistance (p<0.005), and homocysteine (p<0.001). No association was found with other metabolic risk factors or hs-CRP levels. Malondialdehyde (p<0.043) and sVCAM-1 (p<0.002) were positively correlated whereas urinary nitrate/nitrite was negatively correlated (p<0.007). In multiple regression analysis homocysteine, sVCAM-1, and urinary nitrate/nitrite remained independent determinants of resistin levels (R(2) adjusted=0.347, p=0.000). CONCLUSIONS: Resistin could be considered as a promising marker for future cardiovascular disease in obese children.

High-dose daptomycin plus fosfomycin is safe and effective in treating methicillin-susceptible and methicillin-resistant Staphylococcus aureus endocarditis.

We describe 3 patients with left-sided staphylococcal endocarditis (1 with methicillin-susceptible Staphylococcus aureus [MSSA] prosthetic aortic valve endocarditis and 2 with methicillin-resistant S. aureus [MRSA] native-valve endocarditis) who were successfully treated with high-dose intravenous daptomycin (10 mg/kg/day) plus fosfomycin (2 g every 6 h) for 6 weeks. This combination was tested in vitro against 7 MSSA, 5 MRSA, and 2 intermediately glycopeptide-resistant S. aureus isolates and proved to be synergistic against 11 (79%) strains and bactericidal against 8 (57%) strains. This combination deserves further clinical study.

Prevalence of enterotoxins among Escherichia coli isolates causing bacteraemia.

The most frequent cause of bacteraemia among Gram-negative bacteria is Escherichia coli. Analysis of the genes encoding the Shigella enterotoxin 1 (ShET-1), ShET-2, enteroaggregative heat stable toxin 1 (EAST-1) toxins and AggR factor in E. coli strains causing bacteraemia revealed that set1 genes were presented significantly more frequently among quinolone-susceptible strains (P<0.0001), in phylogenetic group B2 (P=0.0004) and in biofilm strains (P=0.02). In contrast, sen genes were significantly more frequent among nalidixic acid-resistant isolates (15% vs. 6%, P=0.046) and in phylogenetic group B1 (P=0.0001). This is the first study in which ShET1, ShET2 and EAST-1 have been found in E. coli collected from blood.

Risk factors and prognosis of nosocomial bloodstream infections caused by extended-spectrum-beta-lactamase-producing Escherichia coli.

Extended-spectrum-beta-lactamase (ESBL)-producing Escherichia coli (ESBLEC) is an increasing cause of community and nosocomial infections worldwide. However, there is scarce clinical information about nosocomial bloodstream infections (BSIs) caused by these pathogens. We performed a study to investigate the risk factors for and prognosis of nosocomial BSIs due to ESBLEC in 13 Spanish hospitals. Risk factors were assessed by using a case-control-control study; 96 cases (2 to 16% of all nosocomial BSIs due to E. coli in the participating centers) were included; the most frequent ESBL was CTX-M-14 (48% of the isolates). We found CTX-M-15 in 10% of the isolates, which means that this enzyme is emerging as a cause of invasive infections in Spain. By repetitive extragenic palindromic sequence-PCR, most isolates were found to be clonally unrelated. By multivariate analysis, the risk factors for nosocomial BSIs due to ESBLEC were found to be organ transplant (odds ratio [OR]=4.8; 95% confidence interval [CI]=1.4 to 15.7), the previous use of oxyimino-beta-lactams (OR=6.0; 95% CI=3.0 to 11.8), and unknown BSI source (protective; OR=0.4; 95% CI=0.2 to 0.9), and duration of hospital stay (OR=1.02; 95% CI=1.00 to 1.03). The variables independently associated with mortality were a Pitt score of >1 (OR=3.9; 95% CI=1.2 to 12.9), a high-risk source (OR=5.5; 95% CI=1.4 to 21.9), and resistance to more than three antibiotics, apart from penicillins and cephalosporins (OR=6.5; 95% CI=1.4 to 30.0). Inappropriate empirical therapy was not associated with mortality. We conclude that ESBLEC is an important cause of nosocomial BSIs. The previous use of oxyimino-beta-lactams was the only modifiable risk factor found. Resistance to drugs other than penicillins and cephalosporins was associated with increased mortality.

Community-onset bacteremia due to extended-spectrum beta-lactamase-producing Escherichia coli: risk factors and prognosis.

BACKGROUND: There is little clinical information about community-onset bloodstream infections (COBSIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (ESBLEC). We investigated the prevalence and risk factors for COBSI due to ESBLEC, and described their clinical features and the impact of COBSI caused by ESBLEC on 14-day mortality. METHODS: Risk factors were assessed using a multicenter case-control-control study. Influence of ESBL production on mortality was studied in all patients with COBSI due to E. coli. Isolates and ESBLs were microbiologically characterized. Statistical analysis was performed using multivariate logistic regression. Thirteen tertiary care Spanish hospitals participated in the study. RESULTS: We included 95 case patients with COBSI due to ESBLEC, which accounted for 7.3% of all COBSI due to E. coli. The ESBL in 83 of these (87%) belonged to the CTX-M family of ESBL, and most were clonally unrelated. Comparison with both control groups disclosed association with health care (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.2-3.8), urinary catheter use (OR, 3.1; 95% CI, 1.5-6.5), and previous antimicrobial use (OR, 2.7; 95% CI, 1.5-4.9) as independent risk factors for COBSI due to ESBLEC. Mortality among patients with COBSI due to ESBLEC was lower among patients who received empirical therapy with beta-lactam/beta-lactam inhibitor combinations or carbapenems (8%-12%) than among those receiving cephalosporins or fluoroquinolones (24% and 29%, respectively). Mortality among patients with COBSI due to E. coli was associated with inappropriate empirical therapy irrespective of ESBL production. CONCLUSIONS: ESBLEC is an important cause of COBSI due to E. coli. Clinicians should consider adequate empirical therapy with coverage of these pathogens for patients with risk factors.

Previous ciprofloxacin exposure is associated with resistance to beta-lactam antibiotics in subsequent Pseudomonas aeruginosa bacteremic isolates.

BACKGROUND: Pseudomonas aeruginosa cross-resistance to ceftazidime, imipenem, meropenem, piperacillin, and fluoroquinoles has been shown in experimental studies, but information regarding its impact in the clinical setting is scarce and inconsistent. The aim of this study was to assess whether previous exposure to ciprofloxacin influences on the sensitivity of those antibiotics in subsequent P aeruginosa bacteremic isolates. METHODS: Patients with P aeruginosa bacteremia were recorded from a blood culture surveillance program (1997-2007). Demographic characteristics, underlying diseases, setting of the infection, source of infection, previous antibiotic exposure, and antibiotic sensitivity were analyzed. RESULTS: We studied 572 cases of P aeruginosa bacteremia. There were 327 men (57.2%), and the mean age was 61.2 +/- 18 years. The bacteremia was nosocomial in 62.4% of episodes. Resistance rates of P aeruginosa isolates were 15.5% for ceftazidime, 16.7% for imipenem, 11.2% for meropenem, 12.3% for piperacillin-tazobactam, and 23.1% for ciprofloxacin. Exposure to ciprofloxacin during the previous 30 days was an independent predictor of resistance to ceftazidime (odds ratio [OR], 3; 95% confidence interval [CI]: 1.7-5.3; P < .001), imipenem (OR, 2; 95% CI: 1.1-3.7; P = .02), meropenem (OR, 2.7; 95% CI: 1.4-5.3; P = .004), piperacillin-tazobactam (OR, 2.4; 95% CI: 1.3-4.7; P = .007), ciprofloxacin (OR, 2.9; 95% CI: 1.7-4.9; P < .001), and multidrug resistance (OR, 2.5; 95% CI: 1.2-5.2; P = .02). CONCLUSION: P aeruginosa bacteremic isolates from patients who have been exposed to ciprofloxacin during the 30 days prior to the development of bacteremia have an increased risk of being resistant to ceftazidime, imipenem, meropenem, piperacillin-tazobactam, or ciprofloxacin and to have multidrug resistance.

Polymorphic receptors of the innate immune system (MBL/MASP-2 and TLR2/4) and susceptibility to pneumococcal bacteremia in HIV-infected patients: a case-control study.

UNLABELLED: Some deficient genetic polymorphisms of the innate immune system have been correlated to a higher susceptibility to different infections, especially in immunocompromised patients. The possible association between an increased incidence of pneumococcal bacteremia in HIV-infected patients, and deficient polymorphisms of the mannose-binding lectin (MBL), MBL-associated serine protease 2 (MASP-2), and toll-like receptors (TLR) 2 and 4 is analyzed by means of a case-control study. CASES: HIV-infected patients with pneumococcal bacteremia. CONTROLS: HIV-infected patients without previous pneumococcal bacteremia matched with cases by sex and CD4 count in a 2:1 ratio. Fifty-seven cases and 114 controls were studied. Demographics, HIV infection status, antiretroviral therapy, risk factors for pneumococcal disease, and genotypes of MBL2, MASP2, TLR2 and TLR4 were analyzed. The prevalence of the MBL2, MASP2, TLR2 and TLR4 gene polymorphisms was similar in both groups. No statistical significance was found (OR 0.77, IC 95% 0.27 - 2.13) when analyzing the possible association of MBL2 deficient polymorphisms with pneumococcal bacteremia. In HIV infected patients, no association between the presence of deficient polymorphisms of MBL2, MASP2, TLR2 and TLR4 and the incidence of pneumococcal bacteremia was found.