Using local epidemiology to make a difficult diagnosis: a case of blastomycosis

OBSERVATIONS ON THE ROENTGEN PATTERNS IN BLASTOMYCOSIS OF BONE A REVIEW OF CASES FROM THE BLASTOMYCOSIS COOPERATIVE STUDY OF THE VETERANS ADMINISTRATION AND DUKE UNIVERSITY MEDICAL CENTERJOHN A. GEHWEILER, M.D., M. PAUL CAPP, M.D. and ERNEST W. CHICK, M.D.Audio Available | Share

Community acquired pneumonia (CAP) is one of the commonest severe and potentially life-threatening infections worldwide. Due to the limitations of microbiological diagnosis initial treatment of CAP is usually empirical, and remains so for a substantial proportion of patients. It is therefore essential that empirical therapy covers all the likely pathogens, which in hospitalized patients in Europe and North America are viral infections (mainly influenza), Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydophila pneumoniae Haemophilus influenzae or Staphylococcus aureus (Table 1). As a consequence European and American guidelines for CAP emphasize empirical treatment with a combination of a β lactam (active against S. pneumoniae, H. influenzae and S. aureus) with a macrolide (active against S. pneumoniae, M. pneumoniae and C. pneumoniae, although S. pneumoniae resistance is an increasing problem), or single-agent therapy with a respiratory fluoroquinolone (active against all the above pathogens). However given the immense variation in climate, geography and social conditions across the world the aetiology of CAP may vary between (and even within) countries, and guidelines suitable for one country may not be suitable for another. Two studies in this issue of Respirology provide further information on the aetiology of CAP in Asia that could influence empirical antibiotic therapy.1,2 C. pneumoniae and M. pneumoniae, along with Legionella pneumophila, Chlamydia psittaci and Coxiella burnetii, are often described as ‘atypical’ organisms due to their intracellular life cycle, the difficulty in culturing them, and because they are not sensitive to β lactams. With the exception of L. pneumophila, atypical organisms are generally considered to cause milder disease than other bacterial causes of CAP, and there has been some controversy whether empirical treatment for CAP should always include cover against atypical organisms. Lui et al. demonstrate that the incidence of CAP due to atypical organisms in a large series of patients admitted to a teaching hospital in Hong Kong was 24%, with the vast majority of infections due to M. pneumoniae and C. pneumoniae.1 The results support other studies from Asia that consistently demonstrate that atypical organisms cause over 20% of cases of CAP admitted to hospital, similar to the incidence in the rest of the world (Table 1). Patients with CAP due to atypical organisms were younger, had less dyspnoea and a lower mortality compared with other bacteria, but nonetheless over 35% had high severity scores (PSI IV or V) and the incidence of admission to intensive care was similar to patients with CAP not caused by atypical organisms.1 In common with other authors, Lui et al. found that clinical parameters could not reliably distinguish CAP caused by atypical organisms from CAP due to other bacteria. Overall this study provides additional data demonstrating CAP due to atypical organisms is common and can be severe, but is difficult to identify clinically. As treatment with empirical antibiotics against atypical organisms is associated with a faster recovery and a 4.1% fall in all cause mortality,3 this suggests empirical therapy for atypical organisms is important in Hong Kong and other Asian centres, as well as in Europe and North America. Although the incidence of CAP due to atypical organisms is remarkably similar across the word, studies in Asian countries clearly indicate that there are often significant differences in the aetiology of CAP to Europe and North America (Table 1). One immediate difference is the significant incidence of pulmonary tuberculosis (TB) presenting as CAP in some Asian countries, which is up to 29% in Hong Kong, Malaysia and Singapore. There are only limited data on viruses as a cause of CAP in Asia, but at least in Japan viral CAP is much less common than in European studies. CAP caused by non-H. influenzae Gram-negative bacteria such as coliforms and Pseudomonas aeruginosa is rare in European studies although causes up to 16% of cases in North America, probably due to a greater preponderance of elderly debilitated patients. In contrast, Gram-negative bacteria are a common cause of CAP in some Asian studies, and are even the predominant cause in Malaysia and Singapore (Table 1), mainly due to a much greater incidence of Klebsiella pneumoniae CAP. The incidence of K. pneumoniae CAP ranges from 4% in Japan to 23% of cases in Malaya, with an average of 15% in a pan-Asian study, compared with <1% in the United Kingdom (Table 1). As well as the high incidence of K. pneumoniae CAP, additional unusual bacterial pathogens can account for a significant proportion of cases of CAP in specific geographic areas. For example, Burkholderia pseudomallei, the cause of meliodosis, accounts for 1–2% of cases of CAP in urban centres in South East Asia, increasing to 32% in rural Thailand. As well as these differences in the endemic causes of CAP, epidemics of less common causes of CAP such as SARS, pneumonic plague (currently active in parts of China) and avian flu often originate in Asia and will be major causes of CAP on occasions. The above data demonstrate that the pathogens causing CAP in Asia can differ to those in Europe and North America, and this is reinforced by the second study published in this edition of Respirology.2 Leo et al. present a case series of eight patients in Singapore presenting with CAP and positive cultures for Acinetobacter baumannii.2A. baumannii is a Gram-negative pathogen that is often considered a skin contaminant and is usually associated only with nosocomial infections, but has also recently been described in US military personnel returning from Iraq and Afghanistan. However, A. baumannii was cultured from both blood and sputum in the majority of patients described by Leo et al., strongly suggesting it was the cause of the infection and supporting epidemiological studies that have shown Acinetobacter causes up to 2% of cases of CAP in several Asian countries (Table 1). Patients with A. baumannii CAP were relatively young and presented in a similar way to severe S. pneumoniae CAP, with a rapid onset of disease, purulent phlegm and lobar infection.2 Most patients had shock and respiratory failure, and the mortality was over 60%. Although this clinical presentation may be skewed by the unreliability of making a diagnosis of A. baumannii infection in the absence of septicaemia, these data suggest it is a cause of severe CAP. Despite its relatively low incidence, the severity of infection combined with the organisms' resistance to first line antibiotics make A. baumannii an important consideration when managing CAP in certain Asian countries. Why should there be a wider range of pathogens causing CAP in Asia? The increased incidence of TB as a cause of CAP in Asia reflects the overall higher incidence of TB compared with Europe and North America, so is perhaps predictable. The reasons causing the increase in K. pneumoniae CAP and occurrence of pathogens such as A. baumannii are less clear. In Europe K. pneumoniae pneumonia is classically associated with alcoholism but this is unlikely to explain the high incidence in some Asian countries. The prevalence of particularly virulent strains of K. pneumoniae may be higher in Asia, and this is supported by the observation that 94% of K. pneumoniae isolates from patients with CAP are mucoid and these strains are more virulent in mouse models of infection.18 Alternatively the increased incidence of K. pneumoniae CAP in Asia may reflect the effects of different environmental conditions on transmission, or possibly an increased frequency of host factors such as abnormal nutritional status, comorbidities or genetic background that may favour K. pneumoniae infection. Similar considerations could also apply to A. baumannii, but this is an environmental organism and the increased incidence of infection in Asia suggests exposure to an environmental reservoir of A. baumannii analogous to the situation with B. pseudomallei CAP. If an environmental source can be identified this may allow preventative measures. Overall, considerably more research is required to characterize why certain organisms are prevalent causes of CAP in some Asian countries. The more immediately practical question is whether the data on aetiology of CAP in Asia should affect management? The high incidence of TB suggests there should be a low threshold for specific microbiological investigations for TB, especially in patients who have had symptoms for longer than 2 weeks, upper lobe disease or cavitation.13 The increased range of bacterial causes of CAP, and in particular the higher incidence of infections with Gram-negative organisms, should probably also influence empirical therapy for CAP in some parts of Asia. For example, K. pneumoniae is often resistant to β lactams and macrolides, and Acinetobacter species are even resistant to some β lactam-stable agents (e.g. coamoxiclav) as well as second generation cephalosporins. CAP due to Gram-negative organisms tends to be more severe than other causes of CAP,19 emphasizing the importance of appropriate empirical therapy. Furthermore, in 25–70% of cases of CAP no microbiological diagnosis can be found, and in Europe these cases are assumed to be mainly due to S. pneumoniae. However, in Asia the larger range of organisms that can cause CAP suggests cases with no microbiological diagnosis will have a more varied aetiology than in Europe, and broader empirical therapy could therefore be necessary. Unfortunately this is likely to have a negative impact on antibiotic resistance and the costs of health care. Differences in the aetiology of CAP between countries could also have additional implications. First, CAP severity scores developed in Europe and North America may not be as useful in Asian patients infected with a different range of organisms. Second, vaccination programmes against S. pneumoniae might be less effective at reducing the incidence of CAP, and could even make empirical treatment more difficult by increasing the relative prevalence of unusual organisms as causes of CAP. The papers in this addition of Respirology shed more light on the causes of CAP in Asia, and how this might affect management. Although primary of importance to Asian countries, in the globalized world of today doctors treating an Asian patient visiting another country need to be aware that CAP could be due to a relatively unusual pathogen. These and other studies demonstrate the importance of each country having local data on the causes of infectious diseases to inform local guidelines, and so avoid potentially sub-optimal empirical therapy.

People are much less aware of the humidity of the air than its temperature. We usually only notice when it is particularly humid or when we get static electricity shocks from metal surfaces because the air is dry. Unlike people, many objects are not much affected by temperature but undergo quite dramatic changes as the relative humididty changes. As we shall see, temperature is extremely important in determining the level of relative humidity, and there is a short section towards the end of the chapter about temperature as an agent of deterioration in its own right.

Empiric Carbapenems for Nosocomial Pneumonia: Is Hindsight Clearer in 2020?

Objective Ceftobiprole is an advance generation cephalosporin which has broad-spectrum bacterial activity (both against Gram-positive and negative pathogens) and was approved for the treatment of community-acquired pneumonia (CAP) and non-ventilated hospital-acquired pneumonia (HAP) in most European countries. We aimed to evaluate the efficacy and safety of ceftobiprole in the treatment of pneumonia in a cohort of severely ill patients admitted to the emergency department (ED). Methods 1-year observational retrospective mono-centric study. Were defined two primary endpoints: first, to evaluate the clinical cure at the test-of-cure (TOC); the second, to evaluate the early improvement, defined as a reduction of symptoms and inflammatory parameters 72 hours after the start of treatment. The secondary endpoint is to evaluate the reduction of antibiotic “burden” using ceftobiprole despite standard of care in severe hospital-acquired pneumonia. Results During the study period, a total of 48 patients with severe pneumonia received ceftobiprole: twenty-two patients (45.8%) as empiric therapy, 9 (18.5%) as a de-escalation option from previous combination therapies, 13 patients (27.1%) as an escalation therapy from ceftriaxone or amoxicillin/clavulanate and four patients (8.3%) as a targeted therapy based on microbiological results. Ceftobiprole mean duration therapy was 10.2 days. Forty-six patients with severe pneumonia had an early clinical improvement 72 hours after the start of treatment (95.8%). In general, ceftobiprole was well tolerated; only one patient suspended the drug because of poor tolerability. The clinical cure at TOC was 85.4% and 30-days crude mortality was 10.4%. Conclusions This study confirms that ceftobiprole is effective in severely ill patients with pneumonia at risk of poor outcomes.

Emergency departments (EDs) play a central role in the evaluation and treatment of sexually transmitted infections, particularly for patients with limited access to outpatient care. National guidelines recommend empiric treatment for Neisseria gonorrhea and Chlamydia trachomatis when clinical concern is present or follow-up cannot be ensured. However, there are limited data on how empiric treatment is applied across pregnancy status and patient demographics in the ED setting. To compare empiric treatment rates between pregnant and nonpregnant patients evaluated for N gonorrhea and C trachomatis infection in EDs and to examine demographic differences in empiric treatment within these groups. Repeated cross-sectional study using aggregate encounter-level data from Epic Cosmos, a national deidentified electronic health record database, from January 1, 2016, to December 31, 2024, of ED patients for whom N gonorrhea or C trachomatis testing was performed. Data were analyzed from January 21 to 25, 2026. Pregnancy status at the time of the ED encounter. The primary outcome was empiric treatment, defined as administration of a guideline-recommended antibiotic regimen for N gonorrhea or C trachomatis infection during the same ED encounter as the testing. Associations between patient characteristics and empiric treatment were estimated using unadjusted odds ratios with 95% CIs, calculated from aggregate counts. Among 4 904 343 ED encounters with N gonorrhea or C trachomatis testing, 49 419 of 454 048 pregnant patients (10.9%) and 1 699 393 of 4 450 295 nonpregnant patients (38.2%) received empiric treatment. Pregnant patients had substantially lower odds of empiric treatment than nonpregnant patients (odds ratio, 0.20; 95% CI, 0.20-0.20). For both pregnant and nonpregnant patients, empiric treatment was more common among younger patients, those with noncommercial insurance, and patients whose primary language was English. Differences by race and ethnicity were observed but varied by pregnancy status. These findings suggest that in a national ED sample, empiric treatment for patients tested for N gonorrhea and C trachomatis differed markedly by pregnancy status and across demographic characteristics. These differences may reflect a combination of guideline interpretation, communication, and structural barriers to follow-up rather than uniform clinician bias. Understanding how empiric treatment aligns with population-level risk and access to care may inform more equitable management of sexually transmitted infections in ED settings.

Preoxygenation and Prevention of Desaturation During Emergency Airway Management

Background Since reaching its nadir in 2000, syphilis has re-emerged as a public health threat in the U.S. The incidence of syphilis is disproportionately high in Atlanta, the epicenter of the HIV epidemic in the U.S. South. Given that syphilis infection is a strong predictor of HIV infection, identifying patients with syphilis is an important and underutilized method for connecting patients to HIV prevention and care services. Emergency departments (EDs) act as a critical access point to care in safety net health systems. We describe the recognition and empiric treatment of syphilis in the ED of Grady Healthcare System, a safety net hospital serving Atlanta. Methods We performed a retrospective chart review on all reactive rapid plasma reagin (RPR) tests collected from patients 18 years and older at the Grady ED from 5/1/20 to 10/31/20. We abstracted reported reason for testing, diagnosis, treatment administered, and location of treatment from the electronic health record. Results From 5/1/20 to 10/31/20, 148 patients with reactive RPR tests were identified. Reasons for testing were broad and included the evaluation of neurologic symptoms (47), genital/anal lesions (31), and a history of syphilis (18) (Table 1). 74 patients had presumed active syphilis (50%), 34 had previously treated syphilis (23%), 12 had false positives (8%), and 28 had an unclear diagnosis (19%) (Table 2). Of those with presumed primary syphilis who were discharged from the ED, 53% (8/15) received empiric treatment in the ED; 59% (10/17) of those with secondary syphilis received empiric treatment prior to discharge. Of the patients discharged from the ED, clinical follow up was indicated for 52% (31/59) given lack of empiric treatment or of confirmed prior treatment. Contact was attempted for 39% (12/31), but only 29% (9/31) were ultimately treated at Grady. Table 1: Abstracted Reasons for Testing for Syphilis in the ED For ED patients from 5/1/20-10/31/20 who had reactive RPRs, reasons for syphilis testing were taken from the chief complaint, history, or medical decision making documentation of ED providers, admitting providers, or consultants. Table 2: Syphilis Diagnoses of ED patients with reactive RPRs ED patients with a positive RPR from 5/1/20-10/31/20 were chart reviewed to determine their diagnosis. Previous RPR, treponemal antibodies, CSF results, media images, progress notes, and descriptions by medical staff were reviewed to attempt to retroactively determine the most likely syphilis diagnosis. Conclusion Reactive RPRs were common in this acute care setting and most represented active syphilis infection. Empiric treatment was most likely to be provided for patients with clear syphilis syndromes. However, a majority of patients who were discharged without empiric treatment did not receive follow up. Institutional protocols for following up reactive tests after discharge represent an opportunity to connect patients with syphilis treatment and HIV prevention services. Disclosures All Authors: No reported disclosures

Treatment and experimental therapeutics of blastomycosis

A CONFUSING CASE OF PNEUMONIA IN A PATIENT WITH HUMAN IMMUNODEFICIENCY VIRUS

Antimicrobial resistance in urinary tract infections at a large urban ED: Factors contributing to empiric treatment failure

133 Sepsis and Empiric Antibiotics: Should We Consider “Health Care Associated” Urinary Tract Infections?

BackgroundComplicated urinary tract infection (cUTI) is a common emergency department (ED) diagnosis. Results of urine culture and antimicrobial susceptibility testing are usually not available for up to 48 hours after an ED visit; therefore, diagnosis and treatment decisions are empiric and based on symptoms, physical findings, and underlying risk of resistance. We sought to understand the epidemiology and incidence of resistance to commonly used oral antibiotics among patients presenting to US EDs with cUTI.MethodsA retrospective multi-center study using data from the Premier Healthcare Database (2013-18) was performed. Inclusion criteria: (1) age ≥ 18 years, (2) primary cUTI ED/inpatient discharge diagnosis, (3) positive blood or urine culture between index ED service days -5 to +2. Transfers from acute care facilities were excluded. We examined rates of resistance to the following drugs/classes: 3rd generation cephalosporins, fluoroquinolones, trimethoprim-sulfamethoxazole, fosfomycin, and nitrofurantoin in patients presenting to the ED, stratified by those who were ultimately admitted as inpatients vs. not. Regional variation by US Census Division was examined.Results187,789 patients met inclusion criteria; 119,668 (63.7%) were admitted to the hospital. 4.6% had positive cultures only with gram-positive bacteria; the remainder had at least one gram-negative pathogen. E. coli was the most common infecting pathogen, present in 72.1% of ED-only infections and 51.4% of those admitted. 44.7% and 58.4% of ED-only and admitted patients, respectively, were resistant to at least 1 of the 5 drugs/classes examined (see table). We saw substantial regional variation; resistance to at least 3 of 5 drugs/classes across all patients ranged from 5.0% in West North Central region to 11.1% in East South Central region (national average: 9.1%).Resistance Rates by Drug/Drug Class and Hospital Admission StatusConclusionPatients with cUTI infections presenting to EDs in the US are frequently resistant to many commonly used oral antibiotics, even in patients not admitted to the hospital. Local epidemiology and resistance should be considered when making empiric treatment decisions in the ED. New oral options for cUTI patients are needed to address the growing challenge of resistance.DisclosuresThomas Lodise, PharmD, PhD, Paratek Pharmaceuticals, Inc. (Consultant) Teena Chopra, MD, MPH, Spero Therapeutics (Consultant, Advisor or Review Panel member) Brian Nathanson, PhD, Spero Therapeutics (Independent Contractor) Katherine Sulham, MPH, Spero Therapeutics (Independent Contractor)

Nosocomial pneumonia or hospital-acquired pneumonia (HAP) causes considerable morbidity and mortality. It is the second most common nosocomial infection and the leading cause of death from hospital-acquired infections. In 1996 the American Thoracic Society (ATS) published guidelines for empirical therapy of HAP. This review focuses on the literature that has appeared since the ATS statement. Early diagnosis of HAP and its etiology is crucial in guiding empirical therapy. Since 1996, it has become clear that differentiating mere colonization from etiologic pathogens infecting the lower respiratory tract is best achieved by employing bronchoalveolar lavage (BAL) or protected specimen brush (PSB) in combination with quantitative culture and detection of intracellular microorganisms. Endotracheal aspirate and non-bronchoscopic BAL/PSB in combination with quantitative culture provide a good alternative in patients suspected of ventilator-associated pneumonia. Since culture results take 2–3 days, initial therapy of HAP is by definition empirical. Epidemiologic studies have identified the most frequently involved pathogens: Enterobacteriaceae, Haemophilus influenzae, Streptococcus pneumoniae and Staphylococcus aureus (‘core pathogens’). Empirical therapy covering only the ‘core pathogens’ will suffice in patients without risk factors for resistant microorganisms. Studies that have appeared since the ATS statement issued in 1996, demonstrate several new risk factors for HAP with multiresistant pathogens. In patients with risk factors, empirical therapy should consist of antibacterials with a broader spectrum. The most important risk factors for resistant microorganisms are late onset of HAP (≥5 days after admission), recent use of antibacterial therapy, and mechanical ventilation. Multiresistant bacteria of specific interest are methicillin-resistant S. aureus (MRSA), Pseudomonas aeruginosa, Acinetobacter calcoaceticus- baumannii, Stenotrophomonas maltophilia and extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. Each of these organisms has its specific susceptibility pattern, demanding appropriate antibacterial treatment. To further improve outcomes, specific therapeutic options for multiresistant pathogens and pharmacological factors are discussed. Antibacterials developed since 1996 or antibacterials with renewed interest (linezolid, quinupristin/dalfopristin, teicoplanin, meropenem, new fluoroquinolones, and fourth-generation cephalosporins) are discussed in the light of developing resistance.Since the ATS statement, many reports have shown increasing incidences of resistant microorganisms. Therefore, one of the most important conclusions from this review is that empirical therapy for HAP should not be based on general guidelines alone, but that local epidemiology should be taken into account and used in the formulation of local guidelines.

Continuous ambulatory peritoneal dialysis (CAPD) is a major form of therapy for chronic end stage renal disease patients, which may lead to CAPD-associated peritonitis. The spectrum of organisms associated with CAPD peritonitis varies geographically. Not much data is available regarding this from southern India. The aim of this study was to characterize the spectrum of organisms associated with CAPD peritonitis in this region and observe the utility of automated blood culture systems to culture peritoneal dialysate. Ninety episodes of peritonitis were cultured over a span of 3 years using an automated blood culture system. The yield of culture positivity was 50%. The most predominant organism was found to be coagulase-negative Staphylococcus spp. (21.1%) followed by Enterobacteriaceae (12.2%). Other organisms isolated were non-fermenting Gram-negative bacilli (4.4%), Pseudomonas aeruginosa (3.3%), α-haemolytic Streptococci (3.3%), Candida spp. (2.2%), Staphylococcus aureus (1.1%), β-haemolytic Streptococci (1.1%) and Micrococci (1.1%). A high degree of resistance to third generation cephalosporins (66.7%) was noted amongst the Gram-negative bacilli. Also, all the Gram-negative bacilli isolated from patients who had prior empirical antibiotic therapy of ceftazidime before arrival at the centre, were resistant to third generation cephalosporins. A varied spectrum of organisms isolated from peritoneal dialysate compared to the global scenario was observed. Also, a high degree of third generation cephalosporin resistance was noted amongst the Gram-negative bacilli. Thus, it is suggested that the empirical therapy should be dependent on the local epidemiology.