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The above patient, suffering from the late disseminated stage of Lyme disease, a tickborne illness, demonstrates apparent Lyme arthritis of the knee.
The term "community acquired" encompasses many infections that may be encountered in clinical practice, although not always on a common basis. The range of diseases embodied by this term continues to evolve in association with the ongoing diversification and aging of the population, climate change, and travel. From the reemergence of vaccine-preventable diseases to sporadic outbreaks of plague[1] to changing presentations of sexually transmitted infections (STIs), community-acquired infections have come under increasing scrutiny in the healthcare community and in the media.
This slideshow will focus on discussions of the following community-acquired conditions:
- Influenza (flu)
- Bacterial pneumonia
- Legionellosis (Legionnaires disease)
- Norovirus infection
- Botulism
- Asymptomatic bacteriuria
- Antimicrobial-resistant infections
- Human immunodeficiency virus (HIV) and viral hepatitis infections
- Lyme disease
- Coronavirus disease 2019 (COVID-19)
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Influenza (Flu)
Since 2010, seasonal influenza has resulted in an estimated 9.3-45 million illnesses in the United States annually, leading to an estimated 140,000-960,000 hospitalizations per year. Between the 2010-2011 and 2017-2018 flu seasons, flu-related deaths are estimated to have ranged from 12,000 to 79,000.[2,3]
Influenza vaccination offers the best available defense, even in years with lower effectiveness. It is recommended for all individuals over the age of 6 months, especially those in high-risk groups.[2] For pregnant women, the protective benefit extends to their newborns; maternal antibodies circulate for the first 6 months of life.[4,5] Healthcare and childcare professionals should receive influenza vaccine annually.[6]
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Flu virions spread up to 6 feet via large respiratory droplets from coughing, sneezing, or talking.[7] However, flu also spreads by people touching contaminated surfaces and then touching their eyes, nose, or mouth. The infection is transmissible for over 24 hours before the onset of symptoms,[7] and 30% or more of flu shedders are asymptomatic altogether.[8] Flu symptoms are typically more severe than those of other viral syndromes, consisting of myalgias, headaches, and occasional gastrointestinal symptoms, as well as fever, cough, nasal congestion, and pharyngitis.[9] Since the 2014-2015 flu season, several states have reported that some flu cases have manifested unusually with parotitis, primarily in children with influenza A (H3) infection.[10]
Those with flu experience downtime and missed productivity, as with any severe viral syndrome; however, a key feature of influenza is its cytopathic effect on upper and lower respiratory columnar epithelium, with the loss of protective cilia.[11] This predisposes to aspiration of pathogenic bacteria that are ordinarily cleared, such as Streptococcus pneumoniae and Staphylococcus aureus (the two most common causes of secondary bacterial pneumonia in flu patients[11]). Influenza also evades host immunity by rapid development of mutations or genetic reassortment among strains.[11]
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The above illustration details "antigenic drift," a mutational phenomenon of the flu virus (shown). It can also be found at https://www.flickr.com/photos/niaid/5102830852/.
Antigenic drift, the process by which the flu virus continually genetically mutates and replicates over time, produces the annual influenza epidemics that sweep across the globe.[12] "Antigenic shift," a larger, occasional, and more abrupt genetic reassortment in influenza A viruses, results in new hemagglutinin or new hemagglutinin and neuraminidase proteins in influenza viruses; the consequences are more severe disease and widespread pandemics (eg, the 2009 H1N1 pandemic).[12]
Type A influenza viruses undergo both antigenic drift and shift, whereas type B influenza viruses undergo the more gradual antigenic drift.[12] In more recent years, H3N2 strains have demonstrated increased antigenic variation and drift, and emergent variants have resulted in reduced effectiveness of flu vaccine against them.[13]
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The above graph shows the percentage of all deaths resulting from pneumonia and influenza in the United States.
Individuals at highest risk for flu complications are those aged 65 years or older, children younger than 5 years (particularly, <2 y), pregnant women, residents of nursing homes/long-term care facilities, Native Americans, and Alaska Natives.[14] In addition, persons with underlying conditions (eg, immune compromise/immunosuppression or cardiovascular, neurologic, endocrine, pulmonary, hepatic, or renal disease) are susceptible. However, a couple of at-risk populations have emerged with unexpected mortality: people with morbid obesity and younger adults.[14] In 2014, US hospitalizations from influenza in individuals aged 18-64 years rose to 61% from 35% in the previous three seasons, with a similar increase in deaths.[15] The 2017-2018 flu season was a high-severity season across all age groups and regions, with the mortality rate attributed to pneumonia and influenza being above 10% for 4 consecutive weeks.[3]
Once flu symptoms begin, individuals at high risk for complications should seek medical care. The diagnosis is primarily clinical, especially as flu season progresses, but during the COVID-19 pandemic, diagnostic analysis of nasopharyngeal swabs became available under US Food and Drug Administration (FDA) emergency use authorization (EUA), including testing for influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19.
Antiviral treatment for influenza with oseltamivir, zanamivir, peramivir, or baloxavir within 48 hours of symptomatic onset may reduce the illness duration and severity, as well as decrease viral shedding.[16] Patients with uncomplicated flu may be treated with supportive care or antiviral agents at their clinician's discretion.
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The above image provides a detailed illustration of the steps in creating the flu vaccine; it can also be found at https://www.flickr.com/photos/niaid/5102236843/.
Misconceptions persist about flu vaccines despite an extensive safety record, including during pregnancy, when women are at higher risk for severe flu complications. Flu vaccination during pregnancy does not require special review or permissions from a healthcare professional. Flu vaccine, whether standard or live attenuated, cannot cause influenza.[17] For all vaccines (not just flu), the incidence of anaphylaxis after administration is 1.31 per 1 million doses, and individuals with egg allergy may safely receive any licensed, age-appropriate flu vaccine. However, those who have had a severe allergic reaction to egg (more serious than hives) should be vaccinated in a medical setting under the supervision of a healthcare provider who is able to recognize and manage a severe allergic reaction.[18]
An estimated two thirds of cases of Guillain-Barré syndrome (GBS), a rare autoimmune disease that affects nerve cells, are triggered by various viral or bacterial pathogens, including influenza.[19] However, there is no definitive association between flu vaccine and GBS; therefore, for the general population, flu vaccination offers the best available protection from flu and GBS. Nonetheless, individuals who have previously had GBS may need to avoid any immune trigger, including vaccinations.[19]
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The radiographs show the progression of pneumonia in a 6-year-old boy infected with the 2009 HIN1 virus. Image A: on admission; B: before methylprednisolone therapy on hospital day 2; and C: 1 day after methylprednisolone treatment.
Bacterial Pneumonia
An estimated 1 million individuals in the United States are hospitalized with bacterial pneumonia every year; about 50,000 die from this disease.[20] Influenza predisposes to secondary bacterial pneumonia and mortality in children and adults, especially those younger than 2 years and persons older than 65 years.[14] Influenza enhances superinfection with S pneumoniae by various means, including mucociliary damage, which reduces mechanical clearance, and neuraminidase-enhanced bacterial adherence.[11] Influenza also sets off a complex immune and inflammatory cascade that increases host susceptibility to bacterial infection.[11]
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S pneumoniae (shown; round, lavender) remains a major cause of community-acquired pneumonia (CAP) and postinfluenza bacterial pneumonia, worldwide;[11,20] however, other common causative pathogens include S aureus, Mycoplasma pneumoniae, Haemophilus influenzae, and Chlamydophila pneumoniae.[21] Of concern is that vaccination of adults against the flu and pneumococcal pneumonia may begin to favor less common culprits isolated in past epidemics, such as Streptococcus pyogenes.[22] In addition, local epidemiology, such as an outbreak of legionellosis, should be considered when choosing empiric CAP therapy. About one third of CAP is caused by respiratory viruses, either alone or concurrently with a bacterial pathogen.
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The introduction of routine pediatric vaccination with the heptavalent pneumococcal conjugate vaccine (PCV7) in 2000 not only reduced pneumococcal pneumonia in children younger than 2 years by 65%, it also reduced all-cause pneumonia in the same age group by 39%.[23] The 13-valent pneumococcal conjugate vaccine (PCV13), introduced in 2010, has continued this trend.[24]
Since its introduction in 1983, the 23-valent pneumococcal polysaccharide vaccine (PPSV23) has been 60-70% effective in preventing invasive pneumococcal disease in adults, but its efficacy is questionable against pneumococcal pneumonia.[25]
As of 2016, the CDC has recommended both PCV13 and PPSV23 for adults aged 65 years or older. PCV13 should be given first, at least 1 year before administration of PPSV23. If the patient has already received PPSV23, administer PCV13 at least 1 year later.[26] If the patient received PPSV23 prior to age 65, a final dose should be given after age 65 at least 5 years from the last.
In older adults, influenza vaccination is up to 60% effective in preventing hospitalization and 80% effective in preventing influenza-related complications.[25] Influenza vaccination has also been found to be 40-60% effective in research evaluating the prevention of bacterial pneumonia that often follows influenza.[27]
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The chest x-ray shows extensive bilateral infiltrates of the lower two thirds of the lung fields in a patient with legionellosis.
Legionellosis (Legionnaires Disease)
In 2015, US cases of Legionella disease cases rose strikingly; this included over 140 cases in Bronx, NY, as related to outbreaks involving a hotel over the summer and in association with water distribution systems in two communities in September.[28] Also, 54 people fell ill at an Illinois veterans home, with 12 deaths,[29] and over 80 inmates were struck at a California state prison.[30] In 2018, the number of US legionellosis cases rose to a record high of 9933.[31] Two outbreaks occurred in Washington Heights, NY; a summer outbreak traced to a cooling tower sickened 27 people, killing one, and a fall outbreak afflicted 32 people, also killing one.[32]
Legionellosis has been a nationally reportable condition since 1976, when an outbreak occurred at a Philadelphia American Legion convention, lending its name to the disease and its causative bacterium.[33] An annual 8000-18,000 US patients are hospitalized with legionellosis.[33] Contributing factors may include increased awareness and screening; climate change, which may promote environmental reservoirs; and an aging population with more risk factors.[34,35] Healthcare facilities, especially long-term care institutions, with large building water systems and a susceptible population, are at risk for healthcare-associated outbreaks. Early recognition and screening, as well as effective water management, may mitigate such risks.[36]
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The above radiograph (left) demonstrates a left hilar mass extending down toward the left lower lobe in a patient with HIV and L pneumophila coinfection. The chest computed tomography (CT) scan (right) shows left-sided pneumonia in the same patient.
Legionella is a common intracellular parasite of amoebae in aquatic environments; it similarly infects human respiratory macrophages.[37] Natural sources of Legionella have not been associated with human disease.[37]L pneumophila multiplies optimally in warm temperatures (77°-108°F [25°-42°C]) and becomes virulent when consumed by amoebae, hijacking enzymatic functions, inhibiting lysosomal fusion, and multiplying in its host. Unable to digest its amplifying meal, the protozoan eventually ruptures, spilling organisms primed with immune-disarming products.[37]
The environmental factors key to human acquisition of Legionella include heat, biofilms, and recent plumbing work; the parasite is then aspirated from the throat or inhaled in aerosols.[36-38] Thermal changes and sheltering biofilms favor overgrowth of L pneumophila.[36] The most common sources of Legionella infection have been associated with large-facility water distribution systems, decorative fountains, misters, cooling towers, hot springs, and drinking water.[38-40] The organism colonizes cooling systems, water heaters, and "dead leg" pipes (noncirculated lines) in facility plumbing systems.[33,36,39] It is not transmitted from person to person.
Presenting symptoms/signs of legionellosis include nonproductive cough, dyspnea, fever, myalgias/headaches, diarrhea, and diffuse to lobar pulmonary infiltrates.[21,33]
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L pneumophila causes 70-92% of US and European laboratory-detected Legionella disease and about 50% of Australian cases.[38] It should be considered in the differential diagnosis of any person with CAP who requires hospitalization, in patients with healthcare-associated pneumonia, in those with immune suppression/immunocompromise, and in individuals who have traveled within the preceding 2 weeks.[33] Heavy smoking, diabetes, renal or liver disease, and chronic lung disease increase not only the likelihood of clinical infection following exposure but also the disease severity. Mortality is 10% in the general population.[41]
Note that hospital ice machines have also been implicated in nosocomial illness; a water reservoir situated near the compressor in these machines may create a warm, favorable environment for growth.[33,40]
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Screening for Legionella is not standard, even with the availability of rapid urinary antigen testing (the most commonly used laboratory test for diagnosis).[42] The diagnosis is best confirmed with urinary antigen assay (70-100% sensitivity, 100% specificity), in addition to sputum and blood cultures on charcoal yeast extract media (20-80% sensitivity, 100% specificity).[42] (At the author's center, Legionella urinary antigen assay is routinely performed as part of a pneumonia protocol order set used by admitting clinicians.)
Culture of clinical isolates is important to correlate with findings from environmental cultures during public health investigations.[42] Other diagnostic tests include paired serology and direct fluorescent antibody (DFA) staining.
Highly effective antibiotics include those commonly used for other respiratory conditions, including azithromycin, trimethoprim-sulfamethoxazole, quinolones, and tetracyclines.[42,43]
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Norovirus Infection
The above graph shows norovirus cases reported to the CDC since 2012 by states participating in the Norovirus Sentinel Testing and Tracking (NoroSTAT) network, including Massachusetts, Michigan, Minnesota, Nebraska, New Mexico, Ohio, Oregon, South Carolina, Tennessee, Virginia, Wisconsin, and Wyoming.
Norovirus causes 58% of US outbreaks of foodborne illness, predominantly between November and April.[44] This pathogen is responsible for 19-21 million US cases of acute gastroenteritis annually, resulting in 56,000-71,000 hospitalizations and 570-800 deaths per year.[44]
Outbreaks typically occur in enclosed populations (notoriously, on cruise ships and in schools), with three quarters taking place in long-term care facilities for the elderly (shown), according to the CDC. Norovirus foodborne outbreaks may occur due to infected food handlers or contaminated foods such as shellfish, fresh fruits, and leafy greens.However, in addition to community-based outbreaks, norovirus is ubiquitous in fresh water and has been identified in ground water and municipal water; it has also been documented to persist in well water for over 3 years.[45]
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Norovirus is spread via contact with contaminated surfaces, direct contact with infected persons, and ingestion of contaminated food and, possibly, drinking water.[44] Although billions of norovirus virions (shown) may be shed in vomitus and stool, an infectious dose may consist of as few as 1-10 viral particles.[45] The virus is swallowed from hands and high-touch surfaces, as well as from aerosolized vomitus within several feet.[46]
About 12-48 hours after exposure, patients experience an acute onset of nausea, vomiting, and nonbloody diarrhea; fever, headaches, and myalgia are not unusual.[46,47] The illness typically resolves within 24-72 hours and is managed with supportive care. The elderly, young children, and immunosuppressed individuals may become severely dehydrated and require hospitalization.[46,47]
Confirmation of the diagnosis is generally made with the use of real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) assay on stool, vomitus, and environmental specimens, collected within 48-72 hours of symptomatic onset.[48,49] Enzyme immunoassays for the detection of the virus in stool samples are also available.[49]
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Strict attention to proper soap-and-water hand hygiene in grouped-care settings is crucial for preventing and reducing the duration of norovirus outbreaks.[47] Infected food handlers should avoid food preparation for at least 48 hours after their symptoms resolve.[46,50]
Thwarting control efforts, norovirus can resist many disinfectants and most hand-sanitizing agents. However, frequent use of a 1000-5000 ppm chlorine bleach solution (5-25 tablespoons of household bleach [5-8%] per gallon of water) or a disinfectant specifically registered as effective against norovirus is effective for cleaning and disinfecting contaminated surfaces.[46,50] This process should be carried out until 48 hours after the last case of gastroenteritis.
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Botulism
Home food preservation has been enjoying a resurgence in the United States,[51] particularly at fall harvest and during the holiday gift-giving season, when home canning is popular. Performed with strict attention to modern techniques, it is safe and rewarding,[52,53] but unsafe methods are sometimes passed along with ancestral recipes or on amateur blogs, and botulism may result.
Botulism is a potentially fatal, progressive neuroparalysis caused by a toxin produced primarily by the obligate anaerobe Clostridium botulinum (although in some cases by C butyricum and C baratii[52,54]) under very specific conditions.[55]C botulinum spores are ubiquitous in soil but are not typical colonizers of the human intestine. While the spores may germinate in the intestine, the normal microbiome often outcompetes clostridial species and limits their survival. However, because infants under age 12 months have not developed this defense, they are much more vulnerable to gut colonization and botulism toxicity.[54,56] Honey is a commonly identified source and should never be fed to a child younger than 1 year.[56] Out of all of the laboratory-confirmed botulism cases reported to the CDC in 2016, 77% occurred in infants.[57]
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The image demonstrates a molecular model of botulinum neurotoxin serotype A.
Botulinum spores are resistant to heat (some strains can survive 5-10 hours in boiling water[55]); thus, most foodborne botulism is related to improperly home-canned vegetables.[57,58] Under anaerobic conditions with low acidity, spores that are not killed will germinate and produce an odorless and flavorless, but potent, neurotoxin.[52,55] Gas and off-odors from other bacteria may be a tip-off to contamination, or the food may appear entirely normal.[52,59]
Fortunately, the botulinum toxin itself is heat-labile and can be destroyed if heated to 176°F (80°C) or higher for 10 minutes;[55] home-canned foods can be rendered safe by boiling for 10 minutes upon opening.[52,59]
A pressure canner should always be used to can certain foods (eg, root vegetables, low-acid fruits/vegetables).[52,59] Some products should never be canned, as they contain pockets of low acidity that cannot be overcome by home-canning methods (eg, pumpkin butter is best eaten fresh or left to commercial processing).[52] Popular homemade gifts of flavored oils using fresh herbs/garlic also pose a risk of botulism if not refrigerated, due to anaerobic conditions within the oil and low acidity.[52,59,60] Reliable instructions and tested recipes can be found in the manufacturer's instructions for canners and canning jars, as well as at the National Center for Home Food Preservation.[59]
The largest US botulism outbreak in almost four decades occurred in April 2015 after an Ohio church potluck meal; tests confirmed the source as potato salad made with home-canned potatoes processed via a boiling water canner (ineffective in killing C botulinum spores) rather than a pressure canner (effectively kills the spores).[61] Of the 29 people who became ill, 11 required ventilator support, and one died.
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Both infants in these images were diagnosed with botulism. The infant on the left had marked loss of muscle tone, especially in the head and neck region. The infant on the right was awake and not sedated but was unable to move or open his eyes. Most US cases of botulism occur in infants.
After a usual incubation period of 18-36 hours, botulism manifests with dry mouth, blurred vision, and diplopia, which may resolve if only a small amount of toxin was ingested.[54,62] Larger inoculations of toxin result in a descending paralysis of peripheral and respiratory muscles, progressing from dysarthria and dysphonia to respiratory failure.[62] With modern intensive support, paralysis slowly resolves over weeks to months as neuromuscular synapses regenerate.[62]
Botulism should be suspected in the setting of acute blurred or double vision, bilateral cranial nerve dysfunction, and descending paralysis; infants present with constipation, poor sucking, poor muscle tone, and respiratory weakness.[54,62] When two or more cases with such presentations are epidemiologically linked, the cause is almost certain to be foodborne botulism.[62] In the absence of a history of honey or canned food consumption, culture any wounds.[62]
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The image depicts botulinum neurotoxin (BoNT) blocking acetylcholine (Ach) release from the neuromuscular junction. Hc = heavy chain; Lc = light chain; SNAP = synaptosome-associated protein.
Electromyography (EMG) produces characteristic findings that help to rule out GBS and myasthenia gravis, which are included in the differential diagnosis of botulism.[54] Culture and toxin detection in specimens of stool, foods, gastric contents, or blood are insensitive but helpful if positive. However, empiric treatment with antitoxin should not await test results.[54]
Supportive care and close monitoring for ventilatory support are essential.[54,62] Weakness and dyspnea may persist for years following recovery. The CDC stocks botulism antitoxin, which may be obtained 24 hours per day, 7 days a week, by contacting their Emergency Operations Center at 770-488-7100.[63] All suspected cases of botulism should be reported to institutional epidemiologists/infection control practitioners and local and state health departments.[63]
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Asymptomatic Bacteriuria
Antimicrobial resistance and its associated morbidity are rising.[64,65] The imperative to reduce unnecessary antibiotic use is a dilemma for many clinicians when faced with incidental pyuria or bacteriuria (or both), yet overwhelming evidence exists that avoiding antibiotics in this circumstance is usually reasonable. The basis of diagnosing urinary tract infection (UTI) has been the presence of nitrites and leukocytes in the urinalysis and bacteriuria of over 100,000 colony-forming units on culture. However, these criteria are only valid if the patient has symptoms.
Asymptomatic bacteriuria (ASB) and pyuria are common with or without bladder catheterization.
Most antibiotics act in the bacterial growth phase,[66] rather than during colonization. The use of antibiotics for ASB does not change the likelihood or severity of subsequent UTIs, while it concurrently poses a risk of adverse drug events, allergic reactions, and Clostridium difficile infection. Furthermore, posttreatment bacteriuria often persists. This situation frequently results in a misdiagnosis of "recurrent UTIs," with repeated prescriptions following recurrent "abnormal" tests-of-cure. Resistance mutations can escalate as well, and patients may be left without oral treatment options in the event of a true UTI or with antibiotic allergies as an added complication.
In the absence of symptoms, avoid urinary studies and tests-of-cure in the healthy pre- or post-menopausal woman, the older adult with functional impairment living in the community, and persons residing in long-term care facilities. Similarly, people with diabetes and those with impaired voiding or indwelling urologic catheters do not benefit from screening or treatment for ASB. The immunosuppressed, including individuals who are neutropenic after chemotherapy, and solid and hematologic organ transplant recipients, need not be screened either. UTI is especially common in recipients of renal transplants and has been thought to precipitate or exacerbate organ rejection. There is little benefit to treating ASB more than 1 month after transplant.[67]
ASB during pregnancy is associated with up to a 30% incidence of pyelonephritis, as well as preterm labor and other obstetric complications. Thus, at least one screening urine culture is recommended early during pregnancy.[67-69]
Evidence supports screening for and treating ASB prior to transurethral resection of the prostate (TURP) and employment of urologic instrumentation in which mucosal bleeding is likely; treating ASB before urologic procedures reduces the incidence of urosepsis. Patients should undergo urine culture within a few days prior to the procedure and receive 1-2 doses of targeted antibiotics based on the result. There is little supporting evidence for routine urinalysis or treatment of ASB prior to nonurologic surgical procedures.[67]
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No recognized "gold standard" exists for the diagnosis of UTI. However, evidence-based guidelines from the Infectious Diseases Society of America (IDSA) define acute UTI as "dysuria, frequency, and/or urgency confirmed by the presence of bacteriuria,"[67] with an alternate definition being "dysuria, frequent voiding of small volumes, and urinary urgency."[70] Delirium in the elderly correlates with UTI in about 25% of cases verified by bacteriuria and clinical response to treatment. However, in the absence of genitourinary symptoms or systemic signs of infection, it is reasonable to assess for all potential causes of acute delirium before initiating empiric antibiotics.[67] Confirmation and treatment of UTI are refined by laboratory findings.
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Antimicrobial-Resistant Infections
In the United States, more than 2 million people become ill from infection with antibiotic-resistant bacteria every year, resulting in over 23,000 deaths,[71] and antimicrobial resistance continues to rise globally.[64,65] Although such resistance is most commonly recognized in bacteria, viruses and fungi are also increasingly affected.
In 2019, the CDC, through its Epidemiology and Laboratory Capacity for Prevention and Control of Emerging Infectious Diseases (ELC) Cooperative Agreement, funded 64 jurisdictions in association with infectious disease detection, prevention, and response.[72] In 2017, the CDC's Antibiotic Resistance (AR) Laboratory Network (AR Lab) identified over 200 unusually resistant pathogens (shown).[73] The CDC estimates that a strategy of rapid identification and containment would prevent 1600 cases of carbapenem-resistant Enterobacteriaceae (CRE) in one state over 3 years.[73] The AR Solutions Initiative was appropriated $170 million in 2020.[74]
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Overuse of antibacterial agents in healthcare has been well recognized, but about 80% of the antibiotics produced in the United States are used in agriculture, contributing heavily to environmental and human exposure.[75,76] Antibiotics have been observed to promote growth by unclear mechanisms (possibly by reducing infection and modifying microbiomes) in animals raised for food, and these agents have been routinely added to feed for years.
Also raising concerns regarding antimicrobial resistance are hospital-associated bacterial infections, which contribute to increasing morbidity and costs of health care, and the fact that in many countries, inexpensive antibiotics may be procured even without a prescription. Broad-spectrum antimicrobial resistance is spreading and increasingly complicating clinical care, and so-called "superbugs," possessing high-level resistance, continue to emerge.
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Carbapenem-resistant Enterobacteriaceae
The gram-negative bacilli of the Enterobacteriaceae family are common causes of community and nosocomial infections. Of particular concern has been the emergence in recent decades of Enterobacteriaceae species producing various extended-spectrum beta lactamases (ESBLs), which has limited treatment in microbes producing these enzymes.[77] Relatively recently, ESBL resistance has been overshadowed by the specter of carbapenem resistance.
Carbapenem resistance is particularly vexing because multiple mechanisms may be involved, including with regard to different classes of ESBLs and carbapenemases (which are an ESBL subtype).[78] The associated resistance genes may accumulate in the same population of bacteria. Some of these genes may be part of the bacterial chromosome, in which case they are passed on to offspring during cell division. Others may be shared between bacteria on plasmids, which are circular pieces of DNA that exist independent of the chromosome.[78] Plasmids may transfer between cells, or they may replicate along with the chromosome during cell division. Most Klebsiella pneumoniae carbapenemase (KPC) producers acquire KPC resistance genes via plasmid transfer. Plasmids in KPC producers spread easily among Klebsiella and Escherichia coli; they often limit treatment to older, more toxic drugs such as colistin and aminoglycosides.[77,79]
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The three-dimensional structure of the protein backbone of New Delhi metallo-beta-lactamase 1 (NDM-1) is shown.
NDM-1 has emerged as an easily shared, plasmid-based gene that confers extensive resistance to all beta lactams, including carbapenems. Furthermore, the plasmid carrying the NDM-1 gene also contains resistance genes for all other antibiotics except tigecycline and colistin.[80] Because the Enterobacteriaceae spread easily via contact and may persist for months in the environment, prevention of nosocomial spread of NDM-1 producers requires strict observance of hand hygiene, contact precautions, and environmental disinfection.[77,81]
The CDC has a detailed graphic describing the public health threat from CRE at http://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf (page 53).
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IVDU/IDU-associated candidemia
The above image depicts the distribution of candidemia cases associated with intravenous drug use (IVDU) and non-IVDU at a Massachusetts tertiary care hospital between 2010 and 2017. (There were no positive blood cultures in January 2017, the last study month.)
Overuse of antibiotics and empiric use of broad-spectrum antibiotics kill or disrupt normal gut flora, allowing opportunists like yeasts to overgrow.[82]Candida albicans causes about half of all candidemias.[82]
The United States is experiencing a resurgence of community-acquired candidemia due to the ongoing opioid epidemic and intravenous/injection drug use (IVDU/IDU).[83]
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Antibiotic stewardship
With the arrival of cool weather and indoor activities, viral infections increase, particularly the common cold (rhinoviruses) and influenza; these infections are common triggers for the misuse and overuse of antibiotics, which are ineffective against viruses.[84] Other viral triggers include respiratory conditions caused by human parainfluenza viruses, respiratory syncytial virus (RSV), adenovirus, and human metapneumovirus;[85,86] these pathogens are also implicated in acute otitis media,[85] which often improves without antibiotics.
Effective strategies for reducing the use of antibiotics for viral syndromes include providing specific instructions for symptom relief and administration of over-the-counter medications. When cooler weather begins, it may be useful to provide patients with instructions detailing symptoms that warrant appointments, as well as a list of symptom relief methods for viral syndromes.
For individuals without chronic lung disease, antibiotics are typically unnecessary, unless the illness persists or worsens beyond 10-14 days with fever and increased or purulent sputum. In cases of acute otitis media, it may be prudent to wait for 48 hours as an alternative to writing an antibiotic prescription; if appropriate, the option of calling in prescriptions if there is no improvement or the condition worsens may be well-received.
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HIV and Viral Hepatitis Infections
The rise of IDU with opioids in recent years, primarily in association with reduced access to prescribed narcotics, has been accompanied by a resurgence of infections with HIV and hepatitis C virus (HCV).[87,88] In addition to encouraging the spread of these infections through needle use, IDU adds to the risk for sexual transmission of these viruses by facilitating coercion and/or trading of drugs for sex, and HIV/HCV coinfection is not uncommon.[89-91]
By the end of 2018, over 1 million adults and adolescents with a diagnosis of HIV were living in the United States and dependent regions,[92] with about 38,000 receiving the diagnosis in 2018.[92,93]
From 2010 to 2016, there was a 3.5-fold increase in the number of new US cases of acute HCV infection,primarily among young white males living in nonurban areas with a history of IDU and use of opioid agonists (eg, oxycodone).[94]
People living with HIV are at risk for more severe hepatitis A and B infections, especially if coinfected with HCV. As of 2020, the CDC recommends screening, vaccination, and post-vaccine confirmation of serologic titers for persons living with HIV. [CDC, People Coinfected with HIV and Viral Hepatitis, September 21, 2020, https://www.cdc.gov/hepatitis/populations/hiv.htm]
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Screening all persons aged 15-65 years for HIV is a grade A recommendation (high certainty of substantial net benefit) of the US Preventive Services Task Force (USPSTF).[95] Since 2006, public health and medical associations have advocated for covering HIV testing as a routine test under general consent for other tests as a key step toward reducing unnecessary barriers to and stigma concerning HIV testing.[95,96]
In addition to routinely screening for HIV infection and other STIs, acute retroviral syndrome should be suspected in any patient of any age presenting with fever and mononucleosis-like symptoms.[97] The acute syndrome coincides with the onset of very high viremia and occurs in the first 2-6 weeks after exposure[97] and prior to HIV antibody seroconversion.
Three types of HIV diagnostic tests are available: antibody differentiation immunoassays, rapid antibody/antigen tests, and nucleic acid tests (NATs).[98] The CDC recommends the use of an FDA-approved instrumented antigen/antibody immunoassay, as it is the most sensitive assay for detecting acute HIV infection.[98] The CDC has provided a chart showing the advantages/disadvantages of FDA-approved HIV assays used for screening, by test category.
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The risk of HIV transmission is especially high in the acute phase. Therefore, inform patients with the diagnosis about the correct use of condoms and discuss abstention from sexual intercourse or limitation of the number of partners, as well as engagement in lower-risk sexual behaviors.[99] The receiving partner in anal intercourse is at highest risk for infection; oral sex confers the lowest risk of transmission.[99]
An important goal of early recognition is halting the chain of HIV transmission, by expediting effective antiretroviral therapy (ART). The 2016 landmark HPTN 052 trial demonstrated a 93% reduction in transmission to seronegative partners when such treatment was started early, at a CD4 count of 350-550 cells/mL.[100,101] No genetically linked HIV transmissions occurred when the HIV viral load was undetectable.[100,101] Other studies support these findings.[100,102]
The "Undetectable = Untransmittable" slogan is a public health campaign that encourages at-risk individuals to seek testing and treatment by emphasizing hope and the chance of a normal life through early and effective care.[95]
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Highly effective and well-tolerated treatments are available for HIV and HCV infection.[103,104] Newer agents for HIV are safer, are taken once daily, and have a higher threshold for viral resistance, allowing more patients to achieve full suppression of their HIV load. Transitioning the patient to early and definitive long-term HIV treatment is critical to halting community transmission and improving the patient's long-term outcomes. Effective ART with undetectable viremia reduces transmission by up to 96%.[100,105]
Performing HIV genotype–resistance testing before starting therapy is important because HIV may still be acquired from treatment-experienced partners who have unsuppressed and resistant virus.[106] Emphasizing that "undetectable equals untransmittable" may enhance compliance with therapy by destigmatizing HIV infection and empowering those living with it.
Some experts have suggested that the up-front cost of treatment mitigates costlier long-term complications and their burden on health care and society. According to the CDC, the lifetime treatment cost for HIV infection in the United States is about $380,000 (in 2010 dollars). A 2018 study found one HCV drug cost $1000 per pill, with the overall cost being $84,000 for a 12-week treatment course, while another such drug cost $23,600 per month.[107,108] Such pricing is a barrier for individuals in the socioeconomic groups most affected by these diseases.
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The White House's National HIV/AIDS Strategy (NHAS), updated for 2020,[109,110] continues the goals of increasing HIV testing and awareness of status, reducing health disparities, increasing access to treatment with full viral suppression, and reducing IDU, among others. Key to reducing long-term healthcare costs is initiation of ART at the time of diagnosis, regardless of absolute CD4 counts; this strategy can decrease not only the risk of transmission but also the risk of progression to opportunistic diseases.[103] Early HIV treatment also lowers the risk of cardiovascular disease, diabetes, and all-cause mortality, by decreasing the chronic inflammation associated with viremia.[103]
The 2020 update adds the goal of increasing the use of preexposure prophylaxis (PrEP),[109,110] which can reduce new HIV infections by up to 92%, even in persons prone to high-risk behavior.[111]
In addition to such objectives, more attention is needed to particularly impacted groups, notably black men who have sex with men, transgender women, and people who live in the Southern United States.[110] Reports of persons illegally selling prescribed antiretrovirals and transmission of HIV resistant to the prophylactic drugs[112] demonstrate the need to ensure treatment compliance in HIV-infected and uninfected individuals in at-risk populations.
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Lyme Disease
The Eastern black legged tick, Ixodes scapularis, is best known for transmitting Lyme disease in the United States; it is distributed throughout the Northeastern, Midwestern, Atlantic, and Gulf states (left map).[113] The Western black legged tick, Ixodes pacificus, transmits Lyme disease along the West coast (right map).[114]
Nymphs of the genus Ixodes are active during warm periods.[115] Although they may feed for a few days before dropping off their host, the nymphs are the size of a poppy seed and often go unnoticed. Adults, which bite during the cooler months, also transmit disease, but they are more likely to be discovered before they can do so.[115]
Three Borrelia species are known to cause Lyme disease in the United States: B burgdorferi, B miyamotoi, and B mayonii.[114] Although the disease is common during warm periods in the Northeastern and Midwestern United States, infected patients may present in nonendemic areas when they travel over the holidays or during vacations. In addition, the seasonal and geographic ranges of Ixodes ticks are expanding due to climate change; Lyme disease is also found in parts of Canada.[116] Thus, it is increasingly important to recognize the potential for tick-borne diseases to occur at any time of year.[117]
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Within 1 month of infection, up to 80% of patients with Lyme disease develop an erythema migrans rash.[116] Over a few days, the rash expands outward from the initial bite and may feature a characteristic bull's-eye appearance (shown). Fever, headache, and lymphadenopathy are common.[116]B mayonii infections also cause nausea and vomiting, as well as diffuse skin lesions and higher blood concentrations of the virus.[117]
Early laboratory test results may be nondiagnostic; therefore, the diagnosis of early Lyme disease is clinical, based on patients' exposure history and suggestive findings. Left untreated, the infection can spread to the nervous system, heart (Lyme carditis), and/or joints.[118] Neurologic complications of Lyme disease include Bell palsy, lymphocytic meningitis, and radiculopathy.[116] Lyme disease is also an important cause of reversible atrioventricular heart block; pacemaker insertion is typically not indicated, as most cases reverse completely with treatment.[119]
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Two-step screening—a C6 antibody enzyme-linked immunoassay (EIA) or C6 immunofluorescence assay (IFA), followed by reflex Western blot testing—remains the most consistently reliable diagnostic measure for Lyme disease.[114,120] In 2019, two-step testing was modified to permit confirmatory testing with EIAs approved by the FDA as having performance equivalent to that of the reflex Western blot. PCR assay testing is the preferred method for detecting B miyamotoi, but it is available only in clinical laboratories, including the Mayo Clinic.[121,122] Commercially available C6 Lyme antibody assay appears to detect B miyamotoi, but mainly in the convalescent phase; further investigation is required.[121,123]
In the absence of symptoms, testing for Lyme disease is not recommended; results may be nondiagnostic and cause confusion, and better assays are needed. Treatment with oral doxycycline, amoxicillin, or cefuroxime for 2 weeks is usually curative for all three species of Borrelia.[118,119,123]
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Prevention of Lyme disease is the best way to address the condition and involves constant tick avoidance.[124,125] Hungry ticks wait at the tops of plants in woods or in low brush or high grasses or are present in leaf litter.[118] Hikers should keep to the center of trails and use insect repellents with known efficacy against ticks, as directed by the manufacturer.[126,127] Products with 20-30% DEET (N,N-diethyl-meta-toluamide) may be used on skin and clothes. Permethrin 0.5% on clothing provides protection even with washing.[126] The US Environmental Protection Agency (EPA) maintains an online search tool for checking the efficacy of common ingredients in insect repellents (https://www.epa.gov/insect-repellents/find-insect-repellent-right-you).
Lyme disease is less likely to be transmitted if the tick is attached for under 24 hours.[118] Prompt showering after hiking permits thorough examination for, and prompt removal of, ticks, which favor creases and crevices, including the navel, the region around the ears, the hair, and areas that may require a mirror to see.[127] Pets and gear should be inspected as well. Heat and drying kills ticks on clothes; dry clothes may be tumbled for 10 minutes at high heat.[127] Alternatives include drying wet clothes for 90 minutes at low heat or at high heat for 60 minutes.[124,128]
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Ticks "cement" themselves into the skin to stay attached,[118] and care should be taken to prevent expulsion of a tick's gut contents into the wound. Remove the tick by grasping it as close to the skin as possible with fine-tipped tweezers and pulling up with steady pressure (shown). Dispose of the tick by flushing it down a toilet or drowning it in rubbing alcohol. Advise patients against crushing ticks with their fingers, as this may transmit pathogens.[127]
Local bite reaction does not imply infection. If the duration of attachment or known exposure is recent but unclear, a one-time oral dose of doxycycline 200 mg no longer than a few days afterward offers effective prophylaxis.[125,129]
Other tick-borne diseases
In addition to Lyme disease, important tick-borne infections include Rocky Mountain spotted fever, anaplasmosis, ehrlichiosis, and babesiosis. Unlike Lyme disease, ticks quickly transmit the pathogens responsible for these illnesses within hours.[130-134]
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COVID-19
Microscopic images of SARS-CoV-2, the virus that causes COVID-19, are shown above.
In late December 2019, SARS-CoV-2, a previously unidentified coronavirus, emerged from Wuhan, China.[135] As of August 12, 2020, COVID-19, the disease caused by this novel betacoronavirus (the same type of virus previously seen in the first known outbreaks of SARS [2003] and Middle East respiratory syndrome [MERS] [2012 to present][136]) had reached global pandemic status.
Presentations of COVID-19 range from asymptomatic/mild symptoms to severe illness and mortality. As of December 14, 2020, there had been over 72 million cases of COVID-19 worldwide, with more than 1.6 million deaths.[137] Symptoms of COVID-19 include fever or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, and diarrhea.[138]
SARS-CoV-2 spreads primarily through droplets of saliva or nasal or oral discharge when an infected person coughs, sneezes, talks, or sings in close proximity to another person.[139] This person-to-person transmission occurs when the droplets contact the mucous membranes—often inadvertently—by touching of the eyes, nose, or mouth with contaminated hands. Awareness and prevention are essential.[139] Everyone should protect themselves and others from infection by frequent handwashing or use of hand sanitizer that is at least 60% alcohol based, as well as by wearing a face mask and not touching the face.[139,140]
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The above x-ray demonstrates a case of COVID-19 pneumonia.
Treatment for COVID-19 has been symptomatic and supportive, but drug therapies are being investigated. In May 2020, the antiviral drug remdesivir was granted US Food and Drug Administration (FDA) EUA for severe COVID-19.[141] Two months later, the US National Institutes of Health (NIH) recommended the corticosteroid dexamethasone for patients requiring supplemental oxygenation or mechanical ventilation.[142]
Among other authorized treatments for COVID-19, the FDA issued an EUA on November 9, 2020, for antibody treatment with bamlanivimab. The authorization permits bamlanivimab to be administered for treatment of mild to moderate COVID-19 in patients aged 12 years or older and weighing at least 40 kg, in whom direct SARS-CoV-2 viral testing has yielded positive results and there is a high likelihood of progression to severe COVID-19 and/or hospitalization.[143] On November 21st, 2020, a similar EAU was issued for antibody treatment with casirivimab/imdevimab.[144]
Among the COVID-19 vaccines being formulated worldwide, Pfizer announced in November 2020 that its product, developed with the German biotechnology company BioNTech, tested 95% effective.[145] Analysis indicated that another vaccine, by Moderna, is 94.1% effective.[146]
The first Western country to authorize use of a COVID-19 vaccine, the United Kingdom approved the Pfizer/BioNTech product on December 2, 2020.[147,148] (Sputnik V, a Russian vaccine, was registered in Russia for emergency use in August 2020, but despite a rollout for inoculation, the vaccine is still in trials for safety and efficacy.[149]) Use of the Pfizer/BioNTech vaccine was subsequently authorized in early December by Bahrain and Canada.[150] Shortly after, on December 11, 2020, the FDA issued an EUA for the vaccine's use in the United States in persons aged 16 years or older.[151] A Chinese-made vaccine, from Sinopharm Group Co., has been in emergency use in a few countries as well, and on December 13, 2020, it was approved in Bahrain for widespread utilization.[152,153]
On December 18, 2020, the Moderna vaccine was also given an FDA EUA, for use in persons aged 18 years or older.[154]
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