Housing data-based socioeconomic index and risk of invasive pneumococcal disease: an exploratory study.

We previously developed and validated an index of socioeconomic status (SES) termed HOUSES (housing-based index of socioeconomic status) based on real property data. In this study, we assessed whether HOUSES overcomes the absence of SES measures in medical records and is associated with risk of invasive pneumococcal disease (IPD) in children. We conducted a population-based case-control study of children in Olmsted County, MN, diagnosed with IPD (1995-2005). Each case was age- and gender-matched to two controls. HOUSES was derived using a previously reported algorithm from publicly available housing attributes (the higher HOUSES, the higher the SES). HOUSES was available for 92·3% (n = 97) and maternal education level for 43% (n = 45). HOUSES was inversely associated with risk of IPD in unmatched analysis [odds ratio (OR) 0·22, 95% confidence interval (CI) 0·05-0·89, P = 0·034], whereas maternal education was not (OR 0·77, 95% CI 0·50-1·19, P = 0·24). HOUSES may be useful for overcoming a paucity of conventional SES measures in commonly used datasets in epidemiological research.

Impact of healthcare-associated acquisition on community-onset Gram-negative bloodstream infection: a population-based study: healthcare-associated Gram-negative BSI.

We performed a population-based study to examine the influence of healthcare-associated acquisition on pathogen distribution, antimicrobial resistance, short- and long-term mortality of community-onset Gram-negative bloodstream infections (BSI). We identified 733 unique patients with community-onset Gram-negative BSI (306 healthcare-associated and 427 community-acquired) among Olmsted County, Minnesota, residents from 1 January 1998 to 31 December 2007. Multivariate logistic regression was used to examine the association between healthcare-associated acquisition and microbiological etiology and antimicrobial resistance. Multivariate Cox proportional hazards regression was used to evaluate the influence of the site of acquisition on mortality. Healthcare-associated acquisition was predictive of Pseudomonas aeruginosa (odds ratio [OR] 3.14, 95% confidence intervals [CI]: 1.59-6.57) and the group of Enterobacter, Citrobacter, and Serratia species (OR 2.23, 95% CI: 1.21-4.21) as causative pathogens of community-onset Gram-negative BSI. Healthcare-associated acquisition was also predictive of fluoroquinolone resistance among community-onset Gram-negative bloodstream isolates (OR 2.27, 95% CI: 1.18-4.53). Healthcare-associated acquisition of BSI was independently associated with higher 28-day (hazard ratio [HR] 3.73, 95% CI: 2.13-6.93) and 1-year mortality (HR 3.60, 95% CI: 2.57-5.15). Because of differences in pathogen distribution, antimicrobial resistance, and outcomes between healthcare-associated and community-acquired Gram-negative BSI, identification of patients with healthcare-associated acquisition of BSI is essential to optimize empiric antimicrobial therapy.

Influence of referral bias on the clinical characteristics of patients with Gram-negative bloodstream infection.

Referral bias can influence the results of studies performed at tertiary-care centres. In this study, we evaluated demographic and microbiological factors that influenced referral of patients with Gram-negative bloodstream infection (BSI). We identified 2919 and 846 unique patients with Gram-negative BSI in a referral cohort of patients treated at Mayo Clinic Hospitals and a population-based cohort of Olmsted County, Minnesota, residents between 1 January 1998 and 31 December 2007, respectively. Multivariable logistic regression analysis was used to determine factors associated with referral. Elderly patients aged ≥80 years with Gram-negative BSI were less likely to be referred than younger patients [odds ratio (OR) 0·43, 95% confidence intervals (CI) 0·30-0·62] as were females (OR 0·63, 95% CI 0·53-0·74). After adjusting for age and gender, bloodstream isolates of Escherichia coli (OR 0·50, 95% CI 0·43-0·58) and Proteus mirabilis (OR 0·49, 95% CI 0·30-0·82) were underrepresented in the referral cohort; and Pseudomonas aeruginosa (OR 2·26, 95% CI 1·70-3·06), Enterobacter cloacae (OR 2·31, 95% CI 1·53-3·66), Serratia marcescens (OR 2·34, 95% CI 1·33-4·52) and Stenotrophomonas maltophilia (OR 17·94, 95% CI 3·98-314·43) were overrepresented in the referral cohort. We demonstrated that demographic and microbiological characteristics of patients with Gram-negative BSI had an influence on referral patterns. These factors should be considered when interpreting results of investigations performed at tertiary-care centres.

Epidemiology and outcome of Gram-negative bloodstream infection in children: a population-based study.

Population-based studies of Gram-negative bloodstream infection (BSI) in children are lacking. Therefore, we performed this population-based investigation in Olmsted County, Minnesota, to determine the incidence rate, site of acquisition, and outcome of Gram-negative BSI in children aged ⩽18 years. We used Kaplan-Meier method and Cox proportional hazard regression for mortality analysis. We identified 56 unique children with Gram-negative BSI during the past decade. The gender-adjusted incidence rate of Gram-negative BSI per 100 000 person-years was 129·7 [95% confidence interval (CI) 77·8-181·6]) in infants, with a sharp decline to 14·6 (95% CI 6·0-23·2) and 7·6 (95% CI 4·3-10·9) in children aged 1-4 and 5-18 years, respectively. The urinary tract was the most commonly identified source of infection (34%) and Escherichia coli was the most common pathogen isolated (38%). Over two-thirds (68%) of children had underlying medical conditions that predisposed to Gram-negative BSI. The overall 28-day and 1-year all-cause mortality rates were 11% (95% CI 3-18) and 18% (95% CI 8-28), respectively. Younger age and number of underlying medical conditions were associated with 28-day and 1-year mortality, respectively. Nosocomial or healthcare-associated acquisition was associated with both 28-day and 1-year mortality.

Risk factor analysis of Histoplasma capsulatum fungemia.

The primary objective of the study was to investigate the risk factors for Histoplasma capsulatum fungemia. We conducted a retrospective case-control study among patients with histoplasmosis seen at Mayo Clinic in Rochester from 1 January 1991 through 31 December 2005. Blood cultures were prepared from specimens obtained from 111 patients with a diagnosis of histoplasmosis of which 55 had demonstrated H. capsulatum fungemia whereas the cultures of the remaining 56 patients were negative. The mean age of the patients was 56 years, of which 70% men and 95% were white. In univariate analysis, immunocompromised status (OR 2.9, P=0.008), peripheral leukocyte count (WBC)<3000 cells/mm(3) (OR 7.3, P<0.001), albumin<3.5 g/ dl (OR 3.1, P=0.018), and Charlson score of>4 (OR 2.9, P=0.022) were associated with H. capsulatum fungemia, but age>55 years was not (OR 1.4, P=0.38). In multivariable analysis, immunocompromised status (OR 2.4, P=0.043) and WBC<3000 cells/mm(3) (OR 6.5, P=0.001) remained significant factors associated with H. capsulatum fungemia. Immunocompromised status and WBC<3000 cells/ mm(3) are independent risk factors for the development of H. capsulatum fungemia.

International Society of Cardiovascular Infectious Diseases Guidelines for the Diagnosis, Treatment and Prevention of Disseminated Mycobacterium chimaera Infection Following Cardiac Surgery with Cardiopulmonary Bypass.

Mycobacterial infection-related morbidity and mortality in patients following cardiopulmonary bypass surgery is high and there is a growing need for a consensus-based expert opinion to provide international guidance for diagnosing, preventing and treating in these patients. In this document the International Society for Cardiovascular Infectious Diseases (ISCVID) covers aspects of prevention (field of hospital epidemiology), clinical management (infectious disease specialists, cardiac surgeons, ophthalmologists, others), laboratory diagnostics (microbiologists, molecular diagnostics), device management (perfusionists, cardiac surgeons) and public health aspects.

Incidence rate and outcome of Gram-negative bloodstream infection in solid organ transplant recipients.

Bacterial infections are common complications of solid organ transplantation (SOT). In this study, we defined the incidence, mortality and in vitro antimicrobial resistance rates of Gram-negative bloodstream infection (BSI) in SOT recipients. We identified 223 patients who developed Gram-negative BSI among a cohort of 3367 SOT recipients who were prospectively followed at the Mayo Clinic (Rochester, MN) from January 1, 1996 to December 31, 2007. The highest incidence rate (IR) of Gram-negative BSI was observed within the first month following SOT (210.3/1000 person-years [95% confidence interval (CI): 159.3-268.3]), with a sharp decline to 25.7 (95% CI: 20.1-32.1) and 8.2 (95% CI: 6.7-10.0) per 1000 person-years between 2 and 12 months and more than 12 months following SOT, respectively. Kidney recipients were more likely to develop Gram-negative BSI after 12 months following transplantation than were liver recipients (10.3 [95% CI: 7.9-13.1] vs. 5.2 [95% CI: 3.1-7.8] per 1000 person-years). The overall unadjusted 28-day all-cause mortality of Gram-negative BSI was 4.9% and was lower in kidney than in liver recipients (1.6% vs. 13.2%, p < 0.001). We observed a linear trend of increasing resistance among Escherichia coli isolates to fluoroquinolone antibiotics from 0% to 44% (p = 0.002) throughout the study period. This increase in antimicrobial resistance may influence the choice of empiric therapy.

Evaluation of antibiotic therapy following valve replacement for native valve endocarditis.

We retrospectively evaluated 105 patients at the Mayo Clinic between 1970 and 2006 with native valve endocarditis who underwent acute valve surgery. The objective was to determine if outcomes differed based on whether they had received an antibiotic regimen recommended for native valve endocarditis or one for prosthetic valve endocarditis. Fifty-two patients had streptococcal and 53 had staphylococcal infections. Patients with each type of infection were divided into two groups: the first received postoperative monotherapy (with a beta-lactam or vancomycin), and the second received combination therapy (with an aminoglycoside for streptococcal infection, and gentamicin and/or rifampin for staphylococcal infection). The duration and types of antibiotics given pre- and postoperatively, valve cultures results, antibiotic-related adverse events, relapses, and mortality rates within 6 months of surgery were analyzed. Cure rates were similar regardless of the regimen administered. With the small number of patients in each group, a multicenter study with a larger cohort of patients is needed to better define optimal postoperative treatment regimens in this population.

Risk of Adverse Reactions to Oral Antibiotics Prescribed by Dentists.

Dentists prescribe a large portion of all oral antibiotics, and these are associated with a risk of adverse drug reactions (ADRs). The aim of this study was to quantify the risk of ADRs associated with oral antibiotics commonly prescribed by dentists. NHS Digital Prescribing data and Yellow Card Drug Analysis data for 2010 to 2017 were abstracted to quantify dental antibiotic prescribing in England, and the rate and types of ADRs associated with them. During the period of study, the mean number of actively practicing dentists in England was 23,624. Amoxicillin accounted for 64.8% of dental antibiotic prescribing and had the lowest reported rate of fatal ADRs (0.1/million prescriptions) and overall ADRs (21.5/million prescriptions). Indeed, amoxicillin was respectively 6 and 3 times less likely to cause an ADR than the other penicillins, penicillin V and amoxicillin + clavulanic acid, and appears to be very safe in patients with no history of penicillin allergy. In contrast, clindamycin, which is often used in patients with penicillin allergy, had the highest rate of fatal (2.9/million prescriptions) and overall (337.3/million prescriptions) ADRs, with Clostridiodes (formerly Clostridium) difficile infections pivotal to its ADR profile. Other amoxicillin alternatives, clarithromycin and metronidazole, while significantly worse than amoxicillin, were 3 and nearly 5 times less likely to cause an ADR than clindamycin. Ranked from least to most likely to cause an ADR, antibiotics most commonly prescribed were as follows: amoxicillin < cephalosporins < erythromycin < tetracyclines < azithromycin < metronidazole < amoxicillin + clavulanic acid < clarithromycin < penicillin V < clindamycin. This study confirmed the high level of safety associated with use of amoxicillin by dentists and the significantly worse rates of fatal and nonfatal ADRs associated with other penicillins and alternatives to amoxicillin for those who are penicillin allergic. In particular, clindamycin had the highest rate of fatal and nonfatal ADRs of any of the antibiotics commonly prescribed by dentists.

Association of serotypes of Streptococcus pneumoniae with disease severity and outcome in adults: an international study.

BACKGROUND: The introduction of conjugate pneumococcal vaccination for children has reduced the burden of invasive disease due to pneumococcal conjugate vaccine (PCV) types (i.e., serotypes 9V, 14, 6B, 18C, 23F, 19F, and 4) in adults. As nonvaccine serotypes become predominant causes of invasive disease among adults, it is necessary to evaluate the disease severity and mortality associated with infection due to nonvaccine serotypes, compared with PCV serotypes, in adults. METHODS: The association of pneumococcal serotype and host-related variables with disease severity and mortality was statistically examined (with multivariable analysis) in 796 prospectively enrolled, hospitalized adult patients with bacteremia due to Streptococcus pneumoniae. RESULTS: In multivariate analyses of risk in patients with invasive pneumococcal disease, older age (age, > or = 65 years; P = .004), underlying chronic disease (P = .025), immunosuppression (P = .035), and severity of disease (P < .001) were significantly associated with mortality; no association was found between nosocomial infection with invasive serotypes 1, 5, and 7 and mortality. The risk factors meningitis (P = .001), suppurative lung complications (P < or = .001), and preexisting lung disease (P = .051) were significantly associated with disease severity, independent of infecting serotype. No differences were seen in disease severity or associated mortality among patients infected with PCV serotypes, compared with patients infected with nonvaccine serotypes. CONCLUSIONS: Our data support the notion that host factors are more important than isolate serotype in determining the severity and outcome of invasive pneumococcal disease and that these outcomes are unlikely to change in association with nonvaccine serotype infection in the post-conjugate vaccine era.

The role of fibronectin binding in the rat model of experimental endocarditis caused by Streptococcus sanguis.

Inactivation of fibronectin (Fn) binding by insertional mutagenesis of Streptococcus sanguis with Tn916 reduces virulence of this bacterium in the rat model of infective endocarditis (IE). Transconjugants were screened for Fn adherence using an ELISA adherence test. One transconjugant had a decreased adherence to immobilized Fn. Southern hybridization demonstrated that the insertion occurred only once in this mutant. The parent strain and mutant strain JL113 were used as challenge strains in a rat endocarditis model. These experiments demonstrated that the mutant had a reduced ability (P less than 0.05) to produce IE. Spontaneous excision of Tn916 from JL113 produced strains identical to both the parental and mutant phenotypes. One strain (JLR-19) that retained the mutant phenotype and one (JLR-15) that regained the parental phenotype for Fn binding were tested for their ability to produce IE. These strains demonstrated that the ability to bind Fn and to produce IE were correlated after Tn916 excision. The reduced virulence of the mutant suggested that adherence of S. sanguis to immobilized Fn plays an important role in the production of IE.

International experts' practice in the antibiotic therapy of infective endocarditis is not following the guidelines.

OBJECTIVE: The management of infective endocarditis (IE) may differ from international guidelines, even in reference centres. This is probably because most recommendations are not based on hard evidence, so the consensus obtained for the guidelines does not represent actual practices. For this reason, we aimed to evaluate this question in the particular field of antibiotic therapy. METHODS: Thirteen international centres specialized in the management of IE were selected, according to their reputation, clinical results, original research publications and quotations. They were asked to detail their actual practice in terms of IE antibiotic treatment in various bacteriological and clinical situations. They were also asked to declare their IE-related in-hospital mortality for the year 2015. RESULTS: The global compliance with guidelines concerning antibiotic therapy was 58%, revealing the differences between theoretical 'consensus', local recommendations and actual practice. Some conflicts of interest were also probably expressed. The adherence to guidelines was 100% when the protocol was simple, and decreased with the seriousness of the situation (Staphylococus spp. 54%-62%) or in blood-culture-negative endocarditis (0%-15%) that requires adaptation to clinical and epidemiological data. CONCLUSION: Worldwide experts in IE management, although the majority of them were involved and co-signed the guidelines, do not follow international consensus guidelines on the particular point of the use of antibiotics.

Coagulase-negative staphylococcal endocarditis. Occurrence in patients with mitral valve prolapse.

Although coagulase-negative staphylococci (CoNS) are frequent etiologic agents in prosthetic valve endocarditis, they rarely infect native heart valves. We report three cases of CoNS endocarditis in patients with mitral valve prolapse (MVP). Review of other reports of MVP-associated endocarditis and of the limited experience with CoNS infection of native heart valves suggests that our experience is not unique. Coagulase-negative staphylococcal endocarditis superimposed on MVP may be difficult to recognize and to treat. The cardiac dysfunction can be quite subtle, the clinical course indolent, the blood culture results difficult to interpret, and the response to antimicrobial agents suboptimal.

Non-group A beta-hemolytic streptococcal cellulitis. Association with venous and lymphatic compromise.

Cellulitis occurring in the limbs of patients who have previously undergone saphenous venectomy and coronary bypass surgery has been the subject of several recent reports. Although isolation of pathogenic microorganisms from these lesions has been uncommon, this report describes three patients who had undergone venectomy previously and in whom non-group A beta-hemolytic streptococci were recovered either during acute episodes of cellulitis or during quiescent intervals. There are to date only four other reported cases of post-venectomy cellulitis from which beta-hemolytic streptococci were isolated: one was non-group A and the others were not serologically characterized. Moreover, studies in patients without bypass who have experienced cellulitis in extremities with compromised venous and/or lymphatic circulation have also yielded a substantial number of non-group A streptococci. The data thus far implicate non-group A beta-hemolytic streptococci as a major cause of cellulitis, especially in the setting of circulatory compromise.

Disseminated histoplasmosis associated with the acquired immune deficiency syndrome.

Disseminated histoplasmosis developed in a previously healthy man as the initial manifestation of the acquired immune deficiency syndrome. Following apparently successful therapy with intravenous amphotericin B, he presented two months later with a subacute pneumonitis syndrome diagnosed by bronchoscopy as Pneumocystis carinii pneumonia. He showed response to intravenous trimethoprim/sulfamethoxazole with resolution of his symptoms and clearing of chest radiographic findings. While he was receiving antibiotics, oral candidiasis developed and has persisted for more than two months despite topical therapy and discontinuation of all antibiotics.

Long-term suppressive therapy for Candida parapsilosis-induced prosthetic valve endocarditis.

Prompt valve replacement is advocated in patients in whom candidal prosthetic valve endocarditis develops. Unfortunately, some patients with this condition are considered nonsurgical candidates, and they are unable to tolerate long-term administration of amphotericin B with or without flucytosine. Herein we describe a patient with Candida parapsilosis-induced prosthetic valve endocarditis in whom oral administration of fluconazole during an 11-month period successfully suppressed the fungal infection. Three previously published cases indicate that long-term noncurative suppressive therapy for C. parapsilosis-induced prosthetic valve endocarditis may allow prolonged symptom-free survival for such patients.

Risk factor assessment for the acquisition of fluoroquinolone-resistant isolates of Pseudomonas aeruginosa in a community-based hospital.

A case-control study was performed in a community-based nonteaching hospital to assess patient risk factors for the acquisition of fluoroquinolone-resistant isolates of Pseudomonas aeruginosa. Fifty-five patients who were hospitalized between July 1, 1993 and December 31, 1993 and who had P. aeruginosa recovered from a clinical specimen were included in the analysis. Two patient populations were designated based on the fluoroquinolone susceptibility of their P. aeruginosa isolates. Statistical evaluation using univariate analysis of demographic and clinical data from the 42 patients with quinolone-susceptible P. aeruginosa and the 13 patients with quinolone-resistant P. aeruginosa demonstrated that prior receipt of a fluoroquinolone was the only significant risk factor for the subsequent emergence of fluoroquinolone resistance among P. aeruginosa isolated from patients hospitalized in this small community-based institution (p = 0.0196). Multivariate analysis supported the finding that prior receipt of a fluoroquinolone was the major risk factor for the isolation of fluoroquinolone-resistant P. aeruginosa (p = 0.0004); isolation of this Gram-negative bacillus from sputum (p = 0.0306) and a history of recent surgery (p = 0.0058) were also significantly associated as risk factors for resistance.

Dual infections with Staphylococcus aureus and Streptococcus pyogenes causing toxic shock syndrome. Possible synergistic effects of toxic shock syndrome toxin 1 and streptococcal pyrogenic exotoxin C.

We describe a 35-year-old woman with clinical, microbiologic, and serologic findings suggesting that the patient developed toxic shock syndrome as a result of dual infections caused by toxin-producing strains of Staphylococcus aureus and Streptococcus pyogenes. Certain aspects of the pathogenesis of this toxin-related syndrome are reviewed.

Comparison of microbiologic characteristics of pathogenic and saprophytic coagulase-negative staphylococci from patients on continuous ambulatory peritoneal dialysis.

Twenty-one microbiologically documented episodes of coagulase-negative staphylococcal peritonitis occurred in 21 continuous ambulatory peritoneal dialysis patients. All strains involved in these infections were tested for antimicrobial susceptibility and in vitro adherence assays. Twenty of the strains were species identified using two commercially available systems. For comparison, 20 saprophytic strains of coagulase-negative staphylococci obtained from the nares and axillae of 10 uninfected, peritoneal dialysis patients were included for in vitro characterization. Staphylococcus epidermidis was the species most often identified for both clinical and saprophytic strains. Eighteen of the 21 (86%) clinical strains were resistant to penicillin G. Methicillin resistance, which was present in five clinical strains, was not found in saprophytic strains. Adherence assay determinations showed marked differences between clinical versus colonization strains, with the clinical isolates significantly more adherent (p less than 0.025) than colonization strains. Electron microscopic examination of silastic catheter segments incubated with a strain of S. epidermidis in used and unused dialysis fluids demonstrated marked differences in attachment of bacteria to catheter material.