Infectious Disease Bacterial Flashcards
Bacterial Disease (13)
Cellulitis Erysipelas Impetigo Pertussis Acute rheumatic fever Botulism Chlamydia Cholera Diphtheria Gonococcal infections Salmonellosis Shigellosis Tetanus
Mycobacterial Disease
Atypical mycobacterial disease
Tuberculosis
Pertussis Epidemiology
United States
1980s cyclical incidence, peaking every 2-5 years
Most cases – June-September
Neither h/o disease nor vaccination provides complete or lifelong immunity
Protection after vaccination wanes in 3-5 years, esp Tdap (DTaP titer not measurable after 12 years)
Milder disease post vaccination
International
Estimated 48.5 million cases
~ 295,000 deaths per year
Case-fatality rate among infants in low-income countries ~ 4%
Pertussis Etiology
B pertussis and B parapertussis - causative agent
Highly contagious
80% of susceptible household contacts become infected after exposure
Family members or relatives suspected source of infection in 75% of cases
Diagnosis of Pertussis
Clinical case definition:
Acute cough lasting at least 14 days with one of paroxysmal cough, posttussive vomiting, or inspiratory whoop
Cough that lasts at least 14 days in an outbreak
Confirmed case
Cough in whichB pertussisis isolated and cultured
Consistent clinical case definition confirmed by polymerase chain reaction (PCR) findings or epidemiologic linkage to a laboratory-confirmed case
PCR - good sensitivity compared to culture, more rapid, may detect later than culture or after antibiotic treatment
Leukocytosis (15,000-50,000 103/µL) with absolute lymphocytosis (not in vaccinated)
Pertussis Pathogenesis
Primarily a toxin-mediated disease
Bacteria attach to cilia of respiratory epithelial cells
Inflammation occurs which interferes with clearance of pulmonary secretions
Pertussis antigens allow evasion of host defenses (lymphocytosis promoted but impaired chemotaxis-move along gradient to organism)
Pertussis Morbidity/Mortality
Complications in infants
69% of infants younger than 6 months with pertussis require hospitalization
13% develop pneumonia, either fromB pertussisinfection or 2nd infection with other pathogens
Seizures and encephalopathy–result from severe paroxysm-induced cerebral hypoxia and apnea, metabolic disturbances such ashypoglycemia, and small intracranial hemorrhage
Reported deaths due to pertussis in young infants have substantially increased over the past 20 years
Pertussis Stage 1
Incubation 3-12 days
Catarrhal phase indistinguishable from URI (nasal congestion, rhinorrhea, sneezing, low-grade fever, tearing)
Most infectious , communicable 3+ weeks after cough onset
Pertussis Stage 2
Paroxysmal phase - paroxysms of intense coughing (lasting up to several minutes)
Older infants and toddlers, paroxysms w/ or w/o whoop
Infants < 6 mo do not have the characteristic whoop, more often apnea, at risk for exhaustion
Posttussive vomiting all to common
Pertussis Stage 3
Convalescent stage - chronic cough lasting weeks to months (hence called 100 day cough in Canada)
Treatment of Pertussis
Antibiotics begun in paroxysmal stage do not affect duration & severity
Antibiotics clear Bordetella pertussiscolonization & prevent spread
1 month or older, macrolide antibiotics (erythromycin, clarithromycin, and azithromycin)
2 mo or older with macrolide allergy - trimethoprim-sulfamethoxazole
Erythromycin and clarithromycin not recommended in infants < 1 mo (increased risk for infantile hypertrophic pyloric stenosis - IHPS)
Azithromycin (less risk for IHPS) < 1 mo
Hospitalization appropriate for Pertussis when?
Infants younger than 3 months
Infants aged 3-6 months, unless observed paroxysms are not severe
Premature young infants; and infants
Children with underlying pulmonary, cardiac, or neuromuscular disease
Droplet precautions are recommended for 5 days after initiation of effective therapy or until 3 weeks after the onset of paroxysms if appropriate antimicrobial therapy is not given
Diagnosis for Acute Rheumatic Fever
combination of clinical manifestations that can develop in relation to group A streptococcal pharyngitis Chorea Carditis Subcutaneous nodules Erythema marginatum Migratory polyarthritis
Acute Rheumatic Fever (ARF)
Incidence of acute rheumatic fever (ARF) has declined in most developed countries
Most clinicians have little or no practical experience with the diagnosis & management of ARF
Etiology of Acute Rheumatic Fever
Heavily encapsulated strains of group A streptococci with rich M protein (a sign of virulence) associated with ARF
Group AStreptococcuscause the myriad of clinical diseases with cross reaction of bacterial antigens with target organs (molecular mimicry)
Autoantibodies reactive against the heart found with rheumatic carditis
Antibody can cross-react with brain and cardiac antigens, and immune complexes are present in the serum (uncertain whether antibodies cause or result of myocardial injury)
ARF Pathophysiology
Migratory arthritis
80% of cases
Large joints - knees, ankles, elbows, or shoulders
Sydenham chorea (St Vitus’ Dance) once common late-onset finding is now rare
Carditis
Progressive CHF, new murmur or pericarditis
May be the presenting sign of unrecognized ARF
Most lethal manifestation
Genetics - increase in family incidence
Associated with class II HLA
Elevated immune-complex levels in patients with ARF associated with HLA-B5
Presentation of ARF
Nonspecific symptoms initially (latent period ~ 18 days (range 1-5 weeks)
Consider carditis if:
New/changing valvular murmurs
Cardiomegaly
Congestive heart failure
Pericarditis
60% with carditis - isolated mitral valve disease, less commonly mitral and aortic valve disease
Sydenham chorea is seldom seen at initial presentation
Erythema marginatum and subcutaneous nodules - < 10% of patients
Arthritis 80% - usually involves multiple large joints: knees, ankles, elbows, and wrists; less often hips and smaller joints of hands and feet
Migratory polyarthritis seen usually when febrile; rarely causes permanent joint deformity
T. Duckett Jones guide to determine high risk
Preceding history of group A strep infection helpful, not required
2 major manifestations or 1 major and 2 minor manifestations
Major manifestations : carditis, polyarthritis, chorea, erythema marginatum & subcutaneous nodules
Minor manifestations include arthralgias & fever
Laboratory –
Elevated ESR and CRP (C-reactive protein)
Prolonged PR interval (not specific/predictive of cardiac sequela
Exceptions to Jones criteria are chorea or possibly indolent carditis
Positive TC for Streptococcus in 25% of patients at the time of presentation
Work up of ARF
– Group A streptococcal antigen detection tests are specific but not very sensitive (90%)
–ASO (antistreptolysin O) – peak titer at onset of rheumatic fever (but not diagnostic of ARF)
– Antistreptococcal antibodies support d/o ARF
– Antibodies target extracellular streptococal products (ASO, antideoxyribonuclease B (anti-DNAse B), antistreptokinase, antihyaluronidase, and anti-DNAase (anti-DNPase))
— Elevated titer of at least one of these antibodies indicates streptococcal infection in 95%
ASO is found in 80-85% of patients with ARF
— Throat culture – sensitivity 25-40% (compared with sensitivity of ASO titer of 80%
— ASO elevated with anti-DNAse B or antihyaluronidase has sensitivity of 90%
— Acute-phase reactants such as C-reactive protein (CRP) and ESR usually elevated; useful monitoring disease
— Synovial fluid analysis reveals a sterile inflammatory reaction, usually with fewer than 20,000 cells/μL (mainly polymorphonuclear) without crystals
ARF – CXR, Echo, ECG
Echocardiography is more sensitive than standard auscultation - detect regurgitant lesions (prognostic significance unclear)
Standard auscultation is however favored for detecting carditis (findings of mitral regurgitation 80%)
Chest radiograph – r/o cardiomegaly
ECG may reveal a prolonged PR interval (not always associated with later cardiac sequelae)
TC may be positive streptococcus
ARF Treatment
Primary goal of treatment is eradicating streptococcal antigens from the pharynx
Penicillin is the drug of choice, parenteral benzathine benzylpenicillin assures compliance
Oral cephalosporins, rather than erythromycin, recommended if allergic to PCN (however 20% cross-reactivity)
Antibiotics do not affect the course an acute attack
Prompt treatment of recurrent strep pharyngitis reduces reactive antigen exposure
Antimicrobial therapy does not alter course/frequency/severity of cardiac disease
Salicylate effective for analgesia (esp high dose–dosage increased until N/V, tinnitus, headache, hyperpnea)
Corticosteroids reserved for severe carditis (tapered after 2-3 weeks)
Mild heart failure treated with rest and corticosteroids
Digoxin in severe carditis (patient may develop heart block, use monitored closely due to potential block)
Nocturnal tachycardia (a sign of cardiac disease) may respond to digoxin, vasodilators or diuretics
Sydenham chorea – haloperidol, also long-term antimicrobial prophylaxis, rest and sedation (chorea disappears with sleep)
AHA Committee on Acute Rheumatic Fever recommends
benzathine benzylpenicillin at 1.2 million units intramuscularly every 4 weeks, every 3 weeks if high-risk
Oral prophylaxis (less reliable) - phenoxymethylpenicillin (penicillin V) or sulfadiazine
Oral cephalosporins recommended if PCN allergic
No consensus on the required duration of antibacterial prophylaxis, AHA recommends:
Risk of recurrence greatest 3-5 years after acute episode
Prophylaxis for at least 10 years after the last episode of rheumatic fever or adult patient
Longer or indefinite prophylaxis if heart disease
Indefinite prophylaxis if high risk for exposure to strep or patients difficult to get follow-up
Botulism Etiology
Acute neuroparalysis due to a neurotoxin produced byClostridium botulinum
C botulinum - gram negative rod survives in soil & water by sporulating, anaerobic conditions allow germination
Toxin binds irreversibly to the presynaptic membranes of peripheral neuromuscular and autonomic nerve junctions (blocks acetylcholine release with weakness, flaccid paralysis)
Cure only occurs following sprouting of new nerve terminals
Different Types of Botulism
Infant botulism(IB) - ingested spores, germinate in intestine producing toxin , bee honey as a source (mortality < 1% with supportive care) Foodborne botulism (FBB) – most often improper canning or home-preparation of foods, more common in adults, 12-36 hours after ingestion develop GI symptoms from gut paralysis then later cranial nerves Wound botulism (WB) – wound contamination with C bolulinum with toxin release (incubation 4-14 days, average 10), typically no GI symptoms (one cause is injection of black-tar heroine) Due to the potency of the toxin, possible use as biological weapon (CBRNE – Botulism)
Botulism Epidemiology
On a molecular weight basis, botulinum toxins are the most potent toxins known
Eight antigenically distinctC botulinumtoxins (A through G),
Each produce only a single toxin type, A & B most potent
Last 20 years, toxin A most common foodborne outbreaks; then toxins B and E
15% ofoutbreaks, the toxin type is not determined
~154 cases of botulism reported to CDC annually
75% infantile botulism (mean age 3 months old - < 1% mortality)
16% foodborne (5-10% mortality)
2 % wound (15-17% mortality)
Botulism Clinical Presentation
> 90% of patients with botulism have 3-5 signs or symptoms: nausea, vomiting, dysphagia,diplopia, dilated/fixed pupils, and an extremely dry mouth unrelieved by drinking fluids
GI – prior to paralysis nonspecific findings (nausea, vomiting, abdominal pain, malaise, dizziness, dry mouth, dry throat, sore throat)
Neurologic – cranial nerves first (except CN 1 and 2), blurred vision, diplopia,ptosis, EOM weakness or paresis, fixed/dilated pupils, dysarthria, dysphagia, and/or suppressed gag reflex, symmetric descending paralysis; weakness of motor & autonomic nerves
Respiratory - muscle weakness may be subtle or progressive, rapid progression to respiratory failure, affected muscles often head/neck, intercostal, diaphragmatic & extremities
Autonomic Nervous System Clinical Presentations of Botulism
Paralytic ileus advancing to severe constipation
Gastric dilatation
Bladder distention advancing to urinary retention
Orthostatic hypotension
Reduced salivation
Reduced lacrimation
Botulism- Workup
CBC – WNL
CSF – WNL
Mouse neutralization bioassay (isolates the botulism toxin from serum, stool, vomitus, gastric aspirate, suspected foods)
Wound cultures for C botulinum
Electromyography (EMG) - reduced amplitude of compound muscle action potentials (nonspecific and non-diagnostic)
Edrophonium chloride (Tensilon) - acetylcholinesterase inhibitor used as test for myasthenia gravis may be falsely positive, typically much less dramatically positive than in patients with myasthenia gravis
Botulism Treatment
Supportive care primarily (resolution ~ 30-100 days)
Respiratory – hygiene, intubation if vital capacity < 30 %
Risk for aspiration pneumonia
GI – suction/hyperalimentation for ileus
Foley for urinary retention
DVT prevention
Debridement of contaminated wountds
Antibiotics
No effect in food born botulism
High dose PCN (alternatives clindamycin or chloramphenical) in wound botulsm
Botulinum antitoxin, heptavalent (HBAT) - investigational antitoxin for naturally occurring non-infant botulism (equine-derived antitoxin with passive antibody (ie immediate immunity) againstC botulinumtoxins A, B, C, D, E, F, and G
Prevention of Botulism
High-temperature pressure cooking eliminates spores from low-acid fruits & vegetables
Boiling for 10 minutes kills bacteria & destroys heat labile botulism toxin, but spores resistant; survive boiling 3-5 hours
Food with botulism toxins usually putrefactive odor, but contaminated food may also look & taste normal
Recommendations:
When preserving food at home, killC botulinumspores by pressure cooking at 250°F (120°C) for 30 minutes
Toxin can be destroyed by boiling for 10 minutes or cooking at 175°F (80°C) for 30 minutes
Do not eat or taste food from bulging cans
Discard food that smells bad
Cessation of intravenous drug use prevents wound botulism (remember just say ‘no’)
3 Types of Chlamydophila that cause pneumonia
Chlamydophila pneumoniae- mild pneumonia or bronchitis in adolescents & young adults, more severe in older adults
Chlamydophila psittaci- psittacosis or ornithosis (preferred term) after exposure to infected birds, clinical spectrum: asymptomatic to fulminant toxic syndrome, present with pneumonia or FUO
C trachomatis- STDs (trachoma,PID, cervicitis) & pneumonia (primarily in infants, young children, immunocompromised adults & lab workers)
Chlamydia trachomatis
Small, gram-negative, obligate intracellular organisms
15 immunotypes
A-C causetrachoma(chronic conjunctivitis endemic in Africa and Asia)
D-K, genital tract infections
L1-L3, lymphogranuloma venereum (associated with genital ulcer disease in tropical countries)
Chlamydia - most commonly reported bacterial STD in US & a leading cause ofinfertilityin women
C pneumoniae pneumonia Epidemiology
300,000 cases per year in US
10-20% of community-acquired pneumonia (CAP) cases among adults
4-year incidence cycle for C pneumoniae pneumonia (although occurs annually)
Highest incidence in 7-40 year olds
More common in males (60-90%) than in females (possibly due to cigarette smoking)
High reinfection among elderly persons
50% of young adults; 75% of elderly persons have serologic evidence of a previous infection
Clinical Presentation of C pneumoniae pneumonia
Incubation period ~ 3-4 weeks
Usually gradual onset that may be biphasic
Most infected persons are asymptomatic or mild respiratory illness
Bronchitis or pneumonia may follow URI symptoms (rhinitis, laryngitis, pharyngitis, sinusitis) in 1-4 weeks
Sputum is usually scant, cough is prominent
Prolonged symptoms (cough and malaise) for weeks to months despite antibiotics
Hoarseness is more common inC pneumoniaeinfection than in mycoplasmal infection or other pneumonias
Headache (58%) – non-classic pneumonia finding
Fever often present first few days, but absent by the time of clinical examination
Pharyngeal erythema without exudate seen in atypical pneumonias; sinus percussion tenderness is more common withC pneumoniae pneumonia
Rhonchi & rales present even in mild disease
C psittaci pneumonia
Anyone exposed to infected birds at risk for infection withC psittaci (found worldwide & year-round, most cases sporadic)
Ornithosis in the US declined after
Introduction of antibiotic-laced bird feed
Quarantine period of 30 days for imported birds
1988-1998, 813 CDC reported cases of psittacosis (70% exposure to pet birds), often not correctly diagnosed or reported
Incubation period 5-14 days or longer
Abrupt onset of constitutional symptoms is common
Severity ranges from asymptomatic to severe pneumonia with systemic illness
Presentation of C psittaci pneumonia
Nonproductive cough has been observed in 50-80%, but often absent initially
Chest pain is common, but pleuritic pain is rare
Ausculatory findings sparse; may underestimate the extent of pneumonia
Fever most common symptom (103-105°F or 39.4-40.5°C), defervescence is usually slow
May present with culture-negative endocarditis or fever of unknown origin
< 50% have photophobia, epistaxis, tinnitus, deafness, gastrointestinal (GI) symptoms & arthralgia
Physical Findings C psittaci pneumonia
Pulse-temperature dissociation (fever without elevated pulse - also seen in Q fever, typhoid fever, & Legionnaires disease)
Somnolence
Splenomegaly
Erythematous, blanching, maculopapular rash (e.g. Horder spots) in the presence of pneumonia (similar to rose spots in typhoid fever)
Meningitis or encephalitis, including focal neurologic deficits and seizures, hepatitis, hemolytic anemia, DIC, reactive arthritis or cutaneous findings (Horder spots (rare), splinter hemorrhages, superficial venous thromboses, acrocyanosis, erythema nodosum)
C trachomatis pneumonia Epidemiology
~ 12,000 cases of pneumonia in infants annually
~ 5-22% pregnant women haveC trachomatisinfection cervical infection
30-50% of neonates exposed at birth become culture positive
15-25% present with clinical conjunctivitis and/or nasopharyngitis, then develop neonatal pneumonitis
~ 11-20% of infants born to infected mothers develop symptomatic pneumonia before 8 wo
C trachomatis pneumonia
Nasal obstruction & discharge, staccato cough, tachypnea (lasting often 3 weeks or more before presentation)
Most afebrile, only moderately ill
Scattered crackles with good breath sounds without wheezing
Conjunctivitis and abnormal middle ear exam in ½ of infants with pneumonia
Adult cases only in immunocompromised
Tests for C pneumoniae pneumonia
IgM titer > 1:16 or 4-fold increase in IgG titer by microimmunofluorescence
Absence of antibodies does not exclude diagnosis (IgM may take 6 weeks, IgG 8 weeks w/ primary infection
PCR - pharyngeal swab, bronchoalveolar lavage, sputum, or tissue used in some labs (less sensitive than IgM)
Cell culture oropharyngeal swabs - best test but only in research labs
CBC usually not elevated
Alkaline phosphate may be elevated
Typically a single subsegmental infiltrate in the lower lobes, consolidation rare, pleural effusions 20-25%, residual changes observed even after 3 months
Testing for C psittaci pneumonia
Paired acute/convalescent sera advised, 3rd sample may be needed
Serologic tests are preferred, culture is difficult & hazardous
CDC case definition
Isolation of organism by culture
Compatible clinical illness with a 4-fold rise in complement fixation (CF) or microimmunofluorecsence (MIF) antibodies againstC psittaci(to a reciprocal titer of 32 or greater by paired sera at least 2 wk apart)
Detection of an IgM titer of 16 or greater againstC psittaciby MIF
CF test can cross-react withC pneumoniae&C trachomatis
MIF & PCR assays can be used to distinguishC psittaci from other chlamydial species
Single lower lobe infiltrate most common finding, also patchy reticular infiltrates, diffuse ground-glass or miliary pattern, small pleural effusions in 50%
Testing for C trachomatis pneumonia
Clinical findings consistent
Confirmation by chlamydial inclusions or elementary bodies on Giemsa-stained smears of the conjunctivae or nasopharynx
Testing of the infants may show findings of elevated antichlamydial IgM titer
CBC with peripheral eosinophilia
Elevated serum immunoglobulin levels characteristic
Should screen the parents for chlamydia & other sexually transmitted diseases
Bilateral interstitial infiltrates with hyperinflation
Chlamydia Pneumonia Treatment
Tetracyclines and macrolides drugs of choice:
Tetracyclines bacteriostatic; inhibit protein synthesis
Macrolides inhibit bacterial growth , possibly blocks dissociation of peptidyl t-RNA from ribosomes, stops protein synthesis
C pneumoniae Pneumonia Treatment
Empiric treatment, lack of rapid testing, in 60% mixed infections present (e.g. pneumococci, mycoplasma, legionellae)
Doxycycline preferred, continue 10-14 days after defervescence
Alternatives - erythromycin/azithromycin/clarithromycin effective; fluoroquinolones less effective
C psittaci Pneumonia Treatment
Tetracycline/doxycycline preferred, treatment 10-21 days
Azithromycin/erythromycin may be less efficacious
C trachomatis pneumonia Treatment
Erythromycin preferred, amoxicillin less effective (TCN not option)
Mother and sexual partner need screening for chlamydia
Chlamydial Genitourinary Infections
Chlamydia infects columnar epithelial cells, adolescent female at more risk, squamocolumnar junction on the ectocervix until early adulthood
Epithelial cells response is neutrophilic infiltration, followed by lymphocytes, macrophages, plasma cells, and eosinophilic invasion
Cytokine and interferon released by epithelial cells induce inflammation
C trachomatis often spread through sexual activity
Infected male - 25% chance per sexual encounter of transmitting the infection to uninfected female
Infected mother – transmission rate to newborn 50-60%, causing conjunctivitis (in most cases) or pneumonia (in 10-20% cases)
Chlamydial Genitourinary Infections Epidemiology
~ 50% infected males and 80% infected females are asymptomatic
Symptomatic infection may cause mucopurulent cervicitis in females & urethritis in males
Ascending infection causes PID in women & most common cause ofepididymitisin men < 35 yo
5-10% women with PID develop perihepatitis (Fitz-Hugh-Curtis syndrome)
40 % of women and 20% of men with chlamydial infection are co-infected with gonorrhea
C trachoma Risk Factors
Nonwhite race
Multiple sexual partners or a new sexual partner
Age 15-24 years (especially age younger than 19 years)
Poor socioeconomic conditions (e.g. homelessness)
Exchange of sex for drugs or money
Single marital status
Intercourse without a barrier contraceptive
History of a previous STD or current coinfection with another STD
Certain cytokine polymorphisms – associated with severe disease and risk of tubal infertility
Certain variants in Toll-like receptor 1 and 4 genes –predispose to infection
Having been a foster child (males only)
Presentation of C trachoma
Women are more likely to be asymptomatic than men (remember 80% vs 50%)
Women also more likely to develop long-term complications (e.g. PID & infertility)
Chlamydia has been isolated in approximately 40-60% of males presenting with nongonococcal urethritis
Epidemiologic studies indicate a high prevalence of asymptomatic men acting as a reservoir for chlamydial infection
Findings for all patients with chlamydial infection:
Possible history of sexually transmitted diseases (STDs)
Dysuria
Yellow mucopurulent discharge from the urethra
Findings for women with chlamydial infection:
Vaginal discharge
Abnormal vaginal bleeding (postcoital or unrelated to menses)
Dyspareunia
History of sexual activity without condoms or condom failure
Proctitis, rectal discharge, or both in cases of receptive anal intercourse
Slow onset and progression of lower abdominal pain
Fever (in pelvic inflammatory disease [PID])
No symptoms (in 80%)
Findings for males with chlamydial infection:
Urethral discharge
History of sexual activity without condoms or condom failure
Proctitis, rectal discharge, or both in cases of receptive anal intercourse
Unilateral pain and swelling of the scrotum
Fever
No symptoms (in 50%)
