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Gardnerella vaginalis colonization and invasive disease of the genitourinary tract in women has been well described. In men, this organism uncommonly causes infection, and bacteremia is rare. We describe 2 cases of G vaginalis bacteremia in men and present a review of the literature. Our 2 patients each had underlying comorbid conditions that predispose to serious bacterial infection. One presented with symptoms of urinary tract infection, the other presented with sepsis. Urine, cultured under usual aerobic conditions, was negative in both cases, but blood cultures after prolonged incubation yielded G vaginalis. Treatment with antibiotics was successful in both cases. Our review of the medical literature revealed 12 previously reported cases of G vaginalis bacteremia in men. Almost all infections in men have originated in the genitourinary tract. Three patients had no reported history of or evidence for disease of the urinary tract, one each with endocarditis, empyema, and odontogenic abscess. Isolation and identification of G vaginalis is often delayed. Selection and duration of treatment have ranged widely in previously reported cases, likely due to the absence of reports on antibiotic susceptibility of G vaginalis and a lack of guidance regarding effective treatment. [ABSTRACT FROM AUTHOR]

Although it varies with age and geographical distribution, the global burden of infection with Streptococcus pneumoniae (pneumococcus) remains considerable. The elderly, and younger adults with comorbid conditions, are at particularly high risk of pneumococcal infection, and this risk will increase as the population ages. Vaccination should be the backbone of our current strategies to deal with this infection. Main body: This manuscript reviews the history of the development of pneumococcal vaccines, and the impact of different vaccines and vaccination strategies over the past 111 years. It documents the early years of vaccine development in the gold mines of South Africa, when vaccination with killed pneumococci was shown to be effective, even before the recognition that different pneumococci were antigenically distinct. The development of type-specific vaccines, still with whole killed pneumococci, showed a high degree of efficacy. The identification of the importance of the pneumococcal capsule heralded the era of vaccination with capsular polysaccharides, although with the advent of penicillin, interest in pneumococcal vaccine development waned. The efforts of Austrian and his colleagues, who documented that despite penicillin therapy, patients still died from pneumococcal infection in the first 96 h, ultimately led to the licensing first of a 14-valent pneumococcal polysaccharide in 1977 followed by the 23-valent pneumococcal polysaccharide in 1983. The principal problem with these, as with other polysaccharide vaccines, was that that they failed to immunize infants and toddlers, who were at highest risk for pneumococcal disease. This was overcome by chemical linking or conjugation of the polysaccharide molecules to an immunogenic carrier protein. Thus began the era of pneumococcal conjugate vaccine (PCV), starting with PCV7, progressing to PCV10 and PCV13, and, most recently, PCV15 and PCV20. However, these vaccines remain serotype specific, posing the challenge of new serotypes replacing vaccine types. Current research addresses serotype-independent vaccines which, so far, has been a challenging and elusive endeavor. Conclusion: While there has been enormous progress in the development of pneumococcal vaccines during the past century, attempts to develop a vaccine that will retain its efficacy for most pneumococcal serotypes are ongoing. [ABSTRACT FROM AUTHOR]

The article challenges the notion that only penicillin should treat neurosyphilis, citing comparative clinical evidence. Topics discussed include the efficacy of penicillin versus ceftriaxone, with studies showing similar or better outcomes for ceftriaxone in terms of CSF normalization and clinical response, questioning the absolute preference for penicillin.

Dexamethasone is another inexpensive generic drug that reduces COVID-19 mortality in patients who require oxygen treatment with or without mechanical ventilation.13 It is not effective in those not receiving respiratory support. ACE inhibitors, ARBs, COVID-19, generic drugs, next pandemic, statins, treatment In an earlier study, combination statin/ACE inhibitor treatment was associated with reduced inflammatory biomarkers in patients with coronary artery bypass surgery.20 1 TABLEObservational studies of the reduction in 28-30-day COVID-19 mortality following inhospital statin treatment and statin withdrawal. Keywords: ACE inhibitors; ARBs; COVID-19; generic drugs; next pandemic; statins; treatment EN ACE inhibitors ARBs COVID-19 generic drugs next pandemic statins treatment 1 4 4 08/17/22 20220801 NES 220801 Scientists are concerned about the origins of SARS-CoV-2, which has caused a devastating global pandemic. [Extracted from the article]

Experiments in animals have played an integral role in furthering basic understanding of the pathophysiology, host immune response, diagnosis, and treatment of infectious diseases. However, competing demands of modern-day clinical training and increasingly stringent requirements to perform animal research have reduced the exposure of infectious disease physicians to animal studies. For practitioners of infectious diseases and, especially, for contemporary trainees in infectious diseases, it is important to appreciate this historical body of work and its impact on current clinical practice. In this article, we provide an overview of some major contributions of animal studies to the field of infectious diseases. Areas covered include transmission of infection, elucidation of innate and adaptive host immune responses, testing of antimicrobials, pathogenesis and treatment of endocarditis, osteomyelitis, intra-abdominal and urinary tract infection, treatment of infection associated with a foreign body or in the presence of neutropenia, and toxin-mediated disease. [ABSTRACT FROM AUTHOR]

Although it varies with age and geographical distribution, the global burden of infection with Streptococcus pneumoniae (pneumococcus) remains considerable. The elderly, and younger adults with comorbid conditions, are at particularly high risk of pneumococcal infection, and this risk will increase as the population ages. Vaccination should be the backbone of our current strategies to deal with this infection. Main body: This manuscript reviews the history of the development of pneumococcal vaccines, and the impact of different vaccines and vaccination strategies over the past 111 years. It documents the early years of vaccine development in the gold mines of South Africa, when vaccination with killed pneumococci was shown to be effective, even before the recognition that different pneumococci were antigenically distinct. The development of type-specific vaccines, still with whole killed pneumococci, showed a high degree of efficacy. The identification of the importance of the pneumococcal capsule heralded the era of vaccination with capsular polysaccharides, although with the advent of penicillin, interest in pneumococcal vaccine development waned. The efforts of Austrian and his colleagues, who documented that despite penicillin therapy, patients still died from pneumococcal infection in the first 96 h, ultimately led to the licensing first of a 14-valent pneumococcal polysaccharide in 1977 followed by the 23-valent pneumococcal polysaccharide in 1983. The principal problem with these, as with other polysaccharide vaccines, was that that they failed to immunize infants and toddlers, who were at highest risk for pneumococcal disease. This was overcome by chemical linking or conjugation of the polysaccharide molecules to an immunogenic carrier protein. Thus began the era of pneumococcal conjugate vaccine (PCV), starting with PCV7, progressing to PCV10 and PCV13, and, most recently, PCV15 and PCV20. However, these vaccines remain serotype specific, posing the challenge of new serotypes replacing vaccine types. Current research addresses serotype-independent vaccines which, so far, has been a challenging and elusive endeavor. Conclusion: While there has been enormous progress in the development of pneumococcal vaccines during the past century, attempts to develop a vaccine that will retain its efficacy for most pneumococcal serotypes are ongoing. [ABSTRACT FROM AUTHOR]

Background Long regarded as the second most common cause of community-acquired pneumonia (CAP), Haemophilus influenzae has recently been identified with almost equal frequency as pneumococcus in patients hospitalized for CAP. The literature lacks a detailed description of the presentation, clinical features, laboratory and radiologic findings, and outcomes in Haemophilus pneumonia. Methods During 2 prospective studies of patients hospitalized for CAP, we identified 33 patients with Haemophilus pneumonia. In order to provide context, we compared clinical findings in these patients with findings in 36 patients with pneumococcal pneumonia identified during the same period. We included and analyzed separately data from patients with viral coinfection. Patients with coinfection by other bacteria were excluded. Results Haemophilus pneumonia occurred in older adults who had underlying chronic lung disease, cardiac conditions, and alcohol use disorder, the same population at risk for pneumococcal pneumonia. However, in contrast to pneumococcal pneumonia, patients with Haemophilus pneumonia had less severe infection as shown by absence of septic shock on admission, less confusion, fewer cases of leukopenia or extreme leukocytosis, and no deaths at 30 days. Viral coinfection greatly increased the severity of Haemophilus , but not pneumococcal pneumonia. Conclusions We present the first thorough description of Haemophilus pneumonia, show that it is less severe than pneumococcal pneumonia, and document that viral coinfection greatly increases its severity. These distinctions are lost when the label CAP is liberally applied to all patients who come to the hospital from the community for pneumonia. [ABSTRACT FROM AUTHOR]

Background: Community-acquired pneumonia (CAP) guidelines have improved the treatment and outcomes of patients with CAP, primarily by standardization of initial empirical therapy. But current society-published guidelines exclude immunocompromised patients.Research Question: There is no consensus regarding the initial treatment of immunocompromised patients with suspected CAP.Study Design and Methods: This consensus document was created by a multidisciplinary panel of 45 physicians with experience in the treatment of CAP in immunocompromised patients. The Delphi survey methodology was used to reach consensus.Results: The panel focused on 21 questions addressing initial management strategies. The panel achieved consensus in defining the population, site of care, likely pathogens, microbiologic workup, general principles of empirical therapy, and empirical therapy for specific pathogens.Interpretation: This document offers general suggestions for the initial treatment of the immunocompromised patient who arrives at the hospital with pneumonia. [ABSTRACT FROM AUTHOR]

Background Intensive studies have failed to identify an etiologic agent in >50% cases of community-acquired pneumonia (CAP). Bacterial pneumonia follows aspiration of recognized bacterial pathogens (RBPs) such as Streptococcus pneumoniae , Haemophilus influenzae , and Staphylococcus aureus after they have colonize the nasopharynx. We hypothesized that aspiration of normal respiratory flora (NRF) might also cause CAP. Methods We studied 120 patients hospitalized for CAP who provided a high-quality sputum specimen at, or soon after admission, using Gram stain, quantitative sputum culture, bacterial speciation by matrix-assisted laser desorption ionization time-of-flight, and viral polymerase chain reaction. Thresholds for diagnosis of bacterial infection were ≥105 colony-forming units (cfu)/mL sputum for RBPs and ≥106 cfu for NRF. Results Recognized bacterial pathogens were found in 68 of 120 (56.7%) patients; 14 (20.1%) of these had a coinfecting respiratory virus. Normal respiratory flora were found in 31 (25.8%) patients; 10 (32.2%) had a coinfecting respiratory virus. Infection by ≥2 RBPs occurred in 10 cases and by NRF together with RBPs in 13 cases. Among NRF, organisms identified as Streptococcus mitis , which share many genetic features of S pneumoniae , predominated. A respiratory virus alone was found in 16 of 120 (13.3%) patients. Overall, an etiologic diagnosis was established in 95.8% of cases. Conclusions Normal respiratory flora, with or without viral coinfection, appear to have caused one quarter of cases of CAP and may have played a contributory role in an additional 10.8% of cases caused by RBPs. An etiology for CAP was identified in >95% of patients who provided a high-quality sputum at, or soon after, the time of admission. [ABSTRACT FROM AUTHOR]

Because of the diverse etiologies of community-acquired pneumonia (CAP) and the limitations of current diagnostic modalities, serum procalcitonin levels have been proposed as a novel tool to guide antibiotic therapy. Outcome data from procalcitonin-guided therapy trials have shown similar mortality, but the essential question is whether the sensitivity and specificity of procalcitonin levels enable the practitioner to distinguish bacterial pneumonia, which requires antibiotic therapy, from viral pneumonia, which does not. In this meta-analysis of 12 studies in 2408 patients with CAP that included etiologic diagnoses and sufficient data to enable analysis, the sensitivity and specificity of serum procalcitonin were 0.55 (95% confidence interval [CI],.37–.71; I 2 = 95.5%) and 0.76 (95% CI,.62–.86; I 2 = 94.1%), respectively. Thus, a procalcitonin level is unlikely to provide reliable evidence either to mandate administration of antibiotics or to enable withholding such treatment in patients with CAP. [ABSTRACT FROM AUTHOR]

The article discusses a study by A. Rouze et al which compared the frequency of bacterial coinfection in patients requiring intensive care unit (ICU) care for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or influenza virus infections. Topics include the use of empiric antibiotics for patients admitted to the hospital for influenza and the result of the study suggesting that bacterial coinfection is less frequent in SARS-CoV-2 or COVID-19 than in influenza pneumonia.

Background: This document provides evidence-based clinical practice guidelines on the management of adult patients with community-acquired pneumonia.Methods: A multidisciplinary panel conducted pragmatic systematic reviews of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations.Results: The panel addressed 16 specific areas for recommendations spanning questions of diagnostic testing, determination of site of care, selection of initial empiric antibiotic therapy, and subsequent management decisions. Although some recommendations remain unchanged from the 2007 guideline, the availability of results from new therapeutic trials and epidemiological investigations led to revised recommendations for empiric treatment strategies and additional management decisions.Conclusions: The panel formulated and provided the rationale for recommendations on selected diagnostic and treatment strategies for adult patients with community-acquired pneumonia. [ABSTRACT FROM AUTHOR]

Background: This document provides evidence-based clinical practice guidelines on the management of adult patients with community-acquired pneumonia. Methods: A multidisciplinary panel conducted pragmatic systematic reviews of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations. Results: The panel addressed 16 specific areas for recommendations spanning questions of diagnostic testing, determination of site of care, selection of initial empiric antibiotic therapy, and subsequent management decisions. Although some recommendations remain unchanged from the 2007 guideline, the availability of results from new therapeutic trials and epidemiological investigations led to revised recommendations for empiric treatment strategies and additional management decisions. Conclusions: The panel formulated and provided the rationale for recommendations on selected diagnostic and treatment strategies for adult patients with community-acquired pneumonia. [ABSTRACT FROM AUTHOR]

Recent studies have shown an association between infections, such as influenza, pneumonia, or bacteremia, and acute cardiac events. We studied the association between foot infection and myocardial infarction, arrhythmia, and/or congestive heart failure. We analyzed the records of 318 consecutive episodes of deep soft tissue infection, gangrene, and/or osteomyelitis in 274 patients referred to a vascular surgery service at a tertiary center. We identified 24 acute cardiac events in 21 of 318 (6.6%) episodes of foot infection or foot gangrene. These 24 events included 11 new myocardial infarctions (3.5%), 8 episodes of new onset or worsening congestive heart failure (2.5%), and 5 new arrhythmias (1.6%). Tachycardia and systemic inflammatory response syndrome were associated with acute cardiac events (P < .05 for each). The 1-year survival of patients with acute cardiac events was 50.4%, significantly lower than the 91.7% 1-year survival of patients without acute cardiac events (P < .0015). Acute cardiac complications are not uncommon among patients presenting with severe foot infection and are associated with a high 1-year mortality. Primary care physicians, cardiologists, and vascular and orthopedic surgeons must keep a high index of suspicion for the occurrence of an acute cardiac event. [ABSTRACT FROM AUTHOR]

The article presents the discussion on treating lower respiratory tract infections especially exacerbations of chronic bronchitis and pneumonia. Topics include third-generation cephalosporins, carbapenems, advanced penicillins, and beta-lactamase blockers; and randomized controlled trials using doxycycline for treating community-acquired pneumonia of mild to moderate severity.

Before 1945, Streptococcus pneumoniae caused more than 90% of cases of pneumonia in adults. After 1950, the proportion of pneumonia caused by pneumococcus began to decline. Pneumococcus has continued to decline; at present, this organism is identified in fewer than fewer 10%-15% of cases. This proportion is higher in Europe, a finding likely related to differences in vaccination practices and smoking. Gram-negative bacilli, Staphylococcus aureus, Chlamydia, Mycoplasma, and Legionella are each identified in 2%-5% of patients with pneumonia who require hospitalization. Viruses are found in 25% of patients, up to one-third of these have bacterial coinfection. Recent studies fail to identify a causative organism in more than 50% of cases, which remains the most important challenge to understanding lower respiratory infection. Our findings have important implications for antibiotic stewardship and should be considered as new policies for empiric pneumonia management are developed. [ABSTRACT FROM AUTHOR]

Murine typhus occurs relatively commonly in southern Texas, as well as in California. We reviewed records of 90 adults and children in whom murine typhus was diagnosed during a 3-year period in 2 hospitals in southern Texas, USA. Most patients lacked notable comorbidities; all were immunocompetent. Initial signs and symptoms included fever (99%), malaise (82%), headache (77%), fatigue (70%), myalgias (68%), and rash (39%). Complications, often severe, in 28% of patients included bronchiolitis, pneumonia, meningitis, septic shock, cholecystitis, pancreatitis, myositis, and rhabdomyolysis; the last 3 are previously unreported in murine typhus. Low serum albumin and elevated procalcitonin, consistent with bacterial sepsis, were observed in >70% of cases. Rash was more common in children; thrombocytopenia, hyponatremia, elevated hepatic transaminases, and complications were more frequent in adults. Murine typhus should be considered as a diagnostic possibility in cases of acute febrile illness in southern and even in more northern US states. [ABSTRACT FROM AUTHOR]

Objectives: The primary objective of this study was to examine the appropriateness of candidemia management at a Veterans Affairs Medical Center as recommended by the 2009 Infectious Diseases Society of America (IDSA) guidelines for treatment of Candida infections. Methods: A retrospective analysis of 94 adult patients with blood cultures positive for Candida spp. was performed. Patients were stratified by severity of disease into two groups: non-neutropenic, mild-moderate disease (Group 1, n = 54, 56%) and non-neutropenic, moderate-severe disease (Group 2, n = 40, 42%). Results: Adherence to the IDSA recommendations for recommended antifungal drug, dose, and duration of therapy was low in both groups (16.7% in Group 1 and 17.5% in Group 2). Although adherence was not associated with higher clinical resolution of infection (P = 0.111), it was associated with a significantly lower mortality rate (P = 0.001) when compared to variance from the guidelines at 6 weeks. Conclusion: Although adherence to published guidelines for treating patients with candidemia was suboptimal at our institution, patients that were managed based on the guidelines had a statistically lower mortality rate. [ABSTRACT FROM AUTHOR]

Background. An elevated white blood cell (WBC) count is a characteristic finding in pneumococcal pneumonia. Very low WBC counts, occurring in some cases, are often associated with overwhelming pneumonia and have been attributed to alcohol-induced suppression of bone marrow. However, a systematic study of neutropenia, leukocytosis, alcohol ingestion, and cirrhosis in pneumococcal pneumonia has not been previously reported. Methods. Using a database of patients with pneumococcal pneumonia at our medical center, we extracted data on WBC counts at admission, differential counts, alcohol ingestion, and cirrhosis, and we related these to 7-day and 30-day mortality. Results. White blood cell counts were <6000/mm3 in 49 of 481 patients (10.2%) with pneumococcal pneumonia and >25 000/mm3 in 40 (8.3%). Mortality at 7 days was 18.4% and 12.5%, respectively, 5-fold and 3-fold greater in patients with WBC <6000 or >25 000 than in those with WBC counts between 6000 and 25 000 (P < .001). Increased band forms were not associated with a worse outcome (P = .12). Alcohol use and cirrhosis were not associated with WBC counts <6000 (P = .63 and P = .41, respectively). Conclusions. In a large series of cases of pneumococcal pneumonia, WBC counts <6000 or >25 000 correlated significantly with increased 7-day mortality. More than 10% band forms was not associated with a poor outcome. Alcohol abuse was not associated with low WBC or increased mortality. Our findings suggest that greater consideration be given to more intense care for patients with bacterial pneumonia who have very high or very low WBC counts at the time of hospital admission. [ABSTRACT FROM AUTHOR]

It is unclear whether concurrent pneumonia and chronic obstructive pulmonary disease (COPD) have a higher mortality than either condition alone. Further, it is unknown how this interaction changes over time. We explored the effect of pneumonia and COPD on inpatient, 30-day and overall mortality. We used a Veterans Health Affairs database to compare patients who were hospitalized for a COPD exacerbation without pneumonia (AECOPD), patients hospitalized for pneumonia without COPD (PNA) and patients hospitalized for pneumonia who had a concurrent diagnosis of COPD (PCOPD). We studied records of 15,065 patients with the following primary discharge diagnoses: (a) AECOPD cohort (7,154 individuals); (b) PNA cohort (4,433 individuals); and (c) PCOPD (3,478 individuals), comparing inpatient, 30-day and overall mortality in the three study cohorts. We observed a stepwise increase in inpatient mortality for AECOPD, PNA and PCOPD (4.8%, 9.5% and 13.2%, respectively). These differences persisted at 30 days post-discharge (AECOPD = 6.7%, PNA = 12.4% and PCOPD = 14.6%;p< 0.0001), but not throughout the study period (median follow-up: 37 months). With time, the death rate rose disproportionally in patients who had been admitted for AECOPD (AECOPD = 64.5%; PNA = 57.4% and PCOPD 66.2%;p< 0.001). In multivariate analysis, PCOPD predicted the greatest inpatient mortality (p< 0.001). The data showed a progression in inpatient and 30-day mortality from AECOPD to PNA to PCOPD. Pneumonia and COPD differentially affected inpatient, 30-day and overall mortality with pneumonia affecting predominantly inpatient and 30-day mortality while COPD affecting the overall mortality. [ABSTRACT FROM PUBLISHER]

Background. Postobstructive community-acquired pneumonia (PO-CAP) is relatively common in clinical practice. The clinical syndrome is poorly defined, and the role of infection as a cause of the infiltrate is uncertain. We prospectively studied patients with PO-CAP and compared them to a cohort of patients with bacterial community-acquired pneumonia (B-CAP). Methods. We prospectively studied patients hospitalized for CAP; 5.4% had PO-CAP, defined as a pulmonary infiltrate occurring distal to an obstructed bronchus. Sputum and blood cultures, viral polymerase chain reaction, urinary antigen tests, and serum procalcitonin (PCT) were done in nearly all cases. Clinical and laboratory characteristics of patients with PO-CAP were compared to those of patients with B-CAP. Results. In a 2-year period, we identified 30 patients with PO-CAP. Compared to patients with B-CAP, patients with PO-CAP had longer duration of symptoms (median, 14 vs 5 days; P < .001). Weight loss and cavitary lesions were more common (P < .01 for both comparisons) and leukocytosis was less common (P < .01) in patients with PO-CAP. A bacterial pathogen was implicated in only 3 (10%) PO-CAP cases. PCT was <0.25 ng/mL in 19 (63.3%) patients. Although no differences were observed in disease severity or rates of intensive care unit admissions, 30-day mortality was significantly higher in PO-CAP vs B-CAP (40.0% vs 11.7%; P < .01). Conclusions. Although there is substantial overlap, PO-CAP is a clinical entity distinct from B-CAP; a bacterial cause was identified in only 10% of patients. Our study has important implications for the clinical recognition of patients with PO-CAP, the role of microorganisms as etiologic agents, and the use of antibiotic therapy. [ABSTRACT FROM AUTHOR]

Rationale: Detection of the C-polysaccharide of Streptococcus pneumoniae in urine by an immune-chromatographic test is increasingly used to evaluate patients with community-acquired pneumonia.Objectives: We assessed the sensitivity and specificity of this test in the largest series of cases to date and used logistic regression models to determine predictors of positivity in patients hospitalized with community-acquired pneumonia.Methods: We performed a multicenter, prospective, observational study of 4,374 patients hospitalized with community-acquired pneumonia.Measurements and Main Results: The urinary antigen test was done in 3,874 cases. Pneumococcal infection was diagnosed in 916 cases (21%); 653 (71%) of these cases were diagnosed exclusively by the urinary antigen test. Sensitivity and specificity were 60 and 99.7%, respectively. Predictors of urinary antigen positivity were female sex; heart rate≥125 bpm, systolic blood pressure<90 mm Hg, and SaO2<90%; absence of antibiotic treatment; pleuritic chest pain; chills; pleural effusion; and blood urea nitrogen≥30 mg/dl. With at least six of all these predictors present, the probability of positivity was 52%. With only one factor present, the probability was only 12%.Conclusions: The urinary antigen test is a method with good sensitivity and excellent specificity in diagnosing pneumococcal pneumonia, and its use greatly increased the recognition of community-acquired pneumonia due to S. pneumoniae. With a specificity of 99.7%, this test could be used to direct simplified antibiotic therapy, thereby avoiding excess costs and risk for bacterial resistance that result from broad-spectrum antibiotics. We also identified predictors of positivity that could increase suspicion for pneumococcal infection or avoid the unnecessary use of this test. [ABSTRACT FROM AUTHOR]

Objectives: Staphylococcus aureus bacteriuria has been associated with invasive S. aureus disease. The current project describes the clinical significance of S. aureus bacteriuria. Methods: We conducted a retrospective chart review of patients who had S. aureus bacteriuria at the Michael E. DeBakey Veterans Affairs Medical Center, 2008-2010. Results: A total of 326 patients were included. Invasive S. aureus disease was documented within 12 months of bacteriuria in 56 patients (22.3% of methicillin-resistant S. aureus (MRSA) cases and 8.4% of methicillin-sensitive S. aureus (MSSA), p = 0.002). Multiple logistic regression indicated that MRSA bacteriuria (odds ratio (OR) 2.91, p = 0.010), absence of symptoms suggestive of a urinary tract infection (UTI) (OR 3.21, p = 0.019), inpatient status (OR 4.72, p = 0.003), and receipt of antibiotics active against S. aureus (OR 6.41, p < 0.001) were significantly associated with the presence of invasive S. aureus disease. Seventy-seven patients (23.6%) died within 12 months of the documented S. aureus bacteriuria. Age (OR 1.02, p = 0.025), absence of pyuria (OR 2.00, p = 0.029), the presence of invasive S. aureus disease (OR 2.05, p = 0.033), and inpatient status (OR 3.62, p < 0.001) were significantly associated with death. Conclusions: S. aureus bacteriuria is associated with significant morbidity and mortality. Patients without UTI symptoms, those with MRSA bacteriuria, and those without pyuria were more to likely to have worse outcomes (invasive S. aureus disease or death). Obtaining blood cultures should be considered in these cases. [ABSTRACT FROM AUTHOR]

Streptococcus pneumoniae is a leading cause of pneumonia, meningitis, and bacteremia, estimated to cause 2 million deaths annually. The majority of pneumococcal mortality occurs in developing countries, with serotype 1 a leading cause in these areas. To begin to better understand the larger impact that serotype 1 strains have in developing countries, we characterized virulence and genetic content of PNI0373, a serotype 1 strain from a diseased patient in The Gambia. PNI0373 and another African serotype 1 strain showed high virulence in a mouse intraperitoneal challenge model, with 20% survival at a dose of 1 cfu. The PNI0373 genome sequence was similar in structure to other pneumococci, with the exception of a 100 kb inversion. PNI0373 showed only 15 lineage specific CDS when compared to the pan-genome of pneumococcus. However analysis of non-core orthologs of pneumococcal genomes, showed serotype 1 strains to be closely related. Three regions were found to be serotype 1 associated and likely products of horizontal gene transfer. A detailed inventory of known virulence factors showed that some functions associated with colonization were absent, consistent with the observation that carriage of this highly virulent serotype is unusual. The African serotype 1 strains thus appear to be closely related to each other and different from other pneumococci despite similar genetic content. [ABSTRACT FROM AUTHOR]

Background: The relationship between invasive medical devices and infective endocarditis (IE) has not been comprehensively assessed. We describe our experience of patients with IE, with particular attention to the role of pre-existing intravascular catheters and implanted cardiac devices in the pathogenesis. Methods: We performed a retrospective review of hospital records over a 10-y period (1997-2007), and included patients with 'definite' or 'possible' IE as per the modified Duke criteria. The complete electronic medical record was reviewed for the presence of intravascular devices prior to the onset of IE, including intravascular catheters and implanted cardiac devices (defibrillators and pacemakers). Results: We identified 155 patients with IE. Infection involved a native valve in 124 (80%) patients and a prosthetic valve in 15 (9.7%). In the remaining 16 (10.3%) patients, infection was attributed to an implanted cardiac device. The most commonly identified source of infection was a central venous catheter, accounting for 17.4% of patients, followed by an implanted cardiac device in 10.3% of patients. Staphylococcus aureus was the most commonly isolated organism in catheter-associated IE and cardiac device-associated IE (31.9% and 62.5%, respectively). Thirty-five (22.5%) patients died within 90 days. Mortality was 31.9% in patients with IE caused by methicillin-resistant S. aureus (MRSA). Conclusions: Intravascular catheters and cardiac implantable devices are common sources of infection leading to IE, and the intracardiac devices themselves often become infected, with MRSA as the predominant pathogen. [ABSTRACT FROM AUTHOR]

Objectives Trimethoprim/sulfamethoxazole effectively treats community-acquired soft tissue infections and urinary tract infections, both of which occur in patients with risk factors for renal impairment. We systematically studied the adverse renal effects of trimethoprim/sulfamethoxazole in a middle-aged veteran population. Methods We reviewed complete electronic records for all patients who, during a 3 year period, had received ≥6 days of treatment with trimethoprim/sulfamethoxazole and for whom a baseline and follow-up determination of serum creatinine and blood urea nitrogen (BUN) were available. Results Of 573 patients who met inclusion criteria, 64 (11.2%) had increases in both serum creatinine and BUN that met predetermined criteria for acute kidney injury (AKI): in 33 (5.8%), AKI was judged likely due to trimethoprim/sulfamethoxazole; in 28 (4.9%), possibly due to trimethoprim/sulfamethoxazole; and in 3 (0.52%), unrelated to trimethoprim/sulfamethoxazole. Five additional patients (0.9%) had elevations only in serum creatinine. In nearly all cases likely due to trimethoprim/sulfamethoxazole, AKI resolved promptly after discontinuation of therapy, but one patient required dialysis. Pyuria appeared in only 2 of 37 patients who had urinalyses; eosinophiluria was not observed. In a multivariate model, patients with hypertension and diabetes mellitus had increased risk for renal insufficiency, especially if these conditions were considered poorly controlled. Conclusions In a middle-aged male inpatient population treated for a minimum of 6 days, AKI is much more common with trimethoprim/sulfamethoxazole therapy than previously reported. Intrinsic renal impairment rather than interstitial nephritis or competition for creatinine clearance appears responsible for the great majority of cases, and neither an effect of dose nor duration was detected in a univariate analysis. Impairment is transient if therapy is discontinued. [ABSTRACT FROM PUBLISHER]

Hantavirus is known to cause 2 distinct clinical syndromes: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome. Seoul virus is an Old World hantavirus known to cause HFRS. We report a case attributed to domestically acquired Seoul hantavirus with prominent pulmonary involvement and a fatal outcome. [ABSTRACT FROM AUTHOR]

Background. Necrotizing pneumonia is generally considered a rare complication of pneumococcal infection in adults. We systematically studied the incidence of necrotizing changes in adult patients with pneumococcal pneumonia and examined the severity of infection, role of causative serotypes, and association with bacteremia. Methods. We used a database of all pneumococcal infections identified at our medical center between 2000 and 2010. Original readings of chest X-rays (CXR) and computerized tomography (CT) were noted. Images were then independently reevaluated by 2 radiologists. The severity of disease at admission was assessed using SMART-COP and Pneumonia Outcomes Research Team (PORT) scoring systems. Results. In 351 cases of pneumococcal pneumonia, necrosis was reported in no (0%) original CXR readings and in 6 of 136 (4.4%) CTs. With rereading, 8 of 351 (2.3%) CXR and 15 of 136 (11.0%) CT had necrotizing changes. Overall, these changes were identified in 23 of 351 (6.6%) patients. The incidence of bacteremia and the admitting SMART-COP and PORT scores were similar in patients with and without necrosis (P = 1.00, P = .32, and P = .54, respectively). Type 3 pneumococcus was more commonly isolated from patients with necrosis than from patients without necrosis (P = .05), but 10 other serotypes were also implicated in 16 cases for which the organism was available for typing. Conclusions. Necrotizing changes in the lungs were seen in 6.6% of a large series of adults with pneumococcal pneumonia but were often overlooked on initial readings. Patients with necrosis were not more likely to have bacteremia or more severe disease. Type 3 pneumococcus was the most commonly identified serotype. [ABSTRACT FROM AUTHOR]

Dyspnea is a common presenting complaint. Trepopnea, an under-recognized form of dyspnea, is difficult breathing in only one lateral decubitus position. One cause of trepopnea is unilateral diaphragmatic paralysis, which in itself is an uncommon diagnosis. We report a unique case of a 55-year-old diabetic man who presented with trepopnea and was found to have unilateral diaphragmatic paralysis secondary to isolated diabetic phrenic neuropathy. This case highlights the importance of recognizing trepopnea as an early clinical symptom of diaphragmatic paralysis and discusses diabetic phrenic neuropathy which can occur in the absence of peripheral neuropathy. [ABSTRACT FROM AUTHOR]

Background: The purpose of this investigation was to determine if disruption of the colonic epithelium during Clostridium difficile infection (CDI) is associated with bacteraemia due to secondary bacterial invasion by enteric organisms. Methods: We reviewed the medical records of 505 randomly selected individuals from a database of patients who tested positive for C. difficile toxin and identified bacteraemias that occurred in 2 periods--the pre-CDI and post-CDI periods. Medical records were reviewed to determine a source for each case of bacteraemia. Staphylococcal bacteraemias were excluded from the analysis. Results: In the pre-CDI period, 28 of 505 (5.5%) patients had non-staphylococcal bacteraemia. A focus of infection was found in 24 of 28 (85.7%) cases. During CDI, 30 of 505 (5.9%) patients had non-staphylococcal bacteraemia; in the majority (19 cases, 63.3%) a focus of infection was not identified ( p < 0.001). In the pre-CDI period, 16 of 28 (57.1%) blood cultures yielded Gram-negative pathogens compared to 9 of 30 (30%) in the CDI period ( p == 0.04). Seven of 28 (25%) blood cultures in the pre-CDI period yielded enterococci compared to 15 of 30 (50%) in the CDI period ( p == 0.05). Conclusions: The incidence of non-staphylococcal bacteraemias in the pre- and post-CDI periods was nearly the same. Cases of bacteraemias in the CDI period more frequently involved organisms of unknown source and uncertain pathogenicity, and were usually not found to require antimicrobial therapy. The data favour the assumption that CDI-associated bacteraemia may be associated with bacterial invasion of the damaged colonic epithelium. [ABSTRACT FROM AUTHOR]

Vaccination with protein-conjugate pneumococcal vaccine (PCV) provides children with extraordinary protection against pneumococcal disease, although the protective effect may be blunted by the emergence of replacement strains. Studies in adults have compared PCV with pneumococcal polysaccharide vaccine (PPV) using surrogate markers of protection, namely, serum anticapsular IgG antibody and opsonic activity. Results suggest that PCV is at least as effective as PPV for the strains covered, but a definitive and consistent advantage has not been demonstrated. Unfortunately, persons who are most in need of vaccine do not respond as well as otherwise healthy adults to either vaccine. Newer formulations of PCV will protect against the most prevalent of the current replacement strains, but replacement strains will create a moving target for PCVs. Unless an ongoing trial comparing 13-valent PCV with placebo (not to PPV) demonstrates a clearly better effect than that seen in the past with PPV, cost-effectiveness considerations are likely to prevent widespread use of PCV in adults. [ABSTRACT FROM AUTHOR]

Background. This study assessed antibody levels for 5 years after primary vaccination or revaccination with 23-valent pneumococcal polysaccharide vaccine (PN23). Methods. Subjects were enrolled into 4 study groups by age (50-64 or ⩾65 years) and prior vaccination status (no prior vaccination or 1 vaccination 3-5 years previously). Blood was obtained on day 0 (before primary vaccination or revaccination), day 30, day 60, and annually during years 2-5. Levels of immunoglobulin G (IgG) to 8 vaccine serotypes were measured by enzyme-linked immunosorbent assay. Results. Of 1008 enrolled subjects, 551 completed year 5. For each serotype and age group, baseline geometric mean concentrations (GMCs) of IgG were higher in revaccination than primary vaccination subjects. Primary vaccination or revaccination with PN23 induced significant increases in levels of antibody to all serotypes tested. Although day 30 and 60 antibody levels tended to be modestly lower after revaccination, study groups had similar GMCs at later time points. For serotypes 4, 6B, 8, 9V, 12F, 14, and 23F, GMCs during years 2-5 after primary vaccination or revaccination remained higher than in vaccine-naive persons. Levels of antibody to serotype 3 returned to baseline by year 2. Conclusions. Both primary vaccination and revaccination with PN23 induce antibody responses that persist during 5 years of observation. [ABSTRACT FROM AUTHOR]