Coccobacilli- facultative anaerobes Notes

Chapter 2 Acyanotic Defects NOTES COCCOBACILLI: FACULTATIVE ANAEROBES MICROBE OVERVIEW ▪ Intermediate shape between cocci (spherical bacteria), bacilli (rod-shaped bacteria) ▪ Gram-negative, facultative anaerobes, nonmotile, nonspore-forming BRUCELLA osms.it/brucella PATHOLOGY & CAUSES ▪ Characteristics ▫ Zoonotic infection ▫ Urease, catalase positive ▫ Facultatively intracellular ▫ Sensitive to heat, ionizing radiation, disinfectants, pasteurization ▪ Virulence factors ▫ Lipopolysaccharide (LPS): promotes cell entry, evasion, intracellular killing ▫ Type IV secretion system (key virulence factor): injection of effector molecules into host cell → modifies endoplasmic reticulum, enables replication ▪ Culture ▫ Isolation specimen: blood, bone marrow, body fluids, tissues ▫ Media: biphasic (solid, liquid) RuizCastaneda blood culture/modern automated blood culture systems (faster, more effective) ▫ Raised, convex colonies with smooth, shiny surface ▪ Causative agent of brucellosis ▪ Most common zoonotic infection to cause disease in humans Transmission ▪ Contact with infected animals (e.g. sheep, cattle, goats, pigs, etc) ▫ Entry of bacteria through skin lesions, conjunctival inoculation, inhalation of contaminated aerosol ▪ Ingestion of contaminated animal products (e.g. unpasteurized milk, cheese; undercooked meat) ▫ Remains viable up to two days in milk at 8°C/46.4°F, three weeks in frozen meat, three months in goat cheese Pathogenesis ▫ Inoculation of bacteria → ingestion by polymorphonuclears, macrophages → passage to local lymph nodes → bacteria replicates intracellularly → some bacteria avoid intracellular killing by different strategies (e.g. inducing phagocyte apoptosis, inhibiting phagocyte-lysosome fusion) → chronic infection TYPES Acute infection ▪ Localized infection (30% of cases), can affect any organ OSMOSIS.ORG 349

▫ Skeletal (most common): arthritis, spondylitis, sacroiliitis, osteomyelitis ▫ Pulmonary: bronchitis, interstitial pneumonitis, lobar pneumonia, pulmonary nodules, pleural effusion, empyema, abscesses ▫ Cardiac: endocarditis, myocarditis, pericarditis, endarteritis ▫ Alimentary: cholecystitis, ileitis, colitis, pancreatitis ▫ Reticuloendothelial: reactive hepatitis, granulomas, acute hepatitis with focal necrosis (B. melitensis), formation of noncaseating sarcoidosis-like granulomas (B. abortus), suppurative abscess formation (B. suis) in liver ▫ Genitourinary: orchitis, epididymitis ▫ Hematological: anemia, leukopenia, thrombocytopenia, pancytopenia, disseminated intravascular coagulation ▫ Neurologic: meningitis, encephalitis, myelitis, radiculitis, neuritis, mycotic aneurysms, brain abscess ▫ Ocular: uveitis, keratoconjunctivitis, corneal ulcers, iridocyclitis, nummular keratitis, choroiditis, optic neuritis, papilledema, endophthalmitis ▫ Dermatologic: nonspecific skin eruptions, ulcerations, petechiae, purpura, granumanifestationslomatous vasculitis, abscesses 350 OSMOSIS.ORG Chronic infection ▪ Symptoms persist one year after diagnosis; localized infection, relapse RISK FACTORS ▪ Occupational exposure ▫ Lab health care workers, farmers, slaughterhouse workers, veterinarians COMPLICATIONS ▪ Infection during pregnancy → intrauterine infection, premature delivery, spontaneous abortion, miscarriage ▪ Endocarditis damage, destroy heart valves ▪ Leading cause of death by brucellosis ▪ Skeletal ▫ May cause long-term damage, bone/ joint malformations ▪ Neurologic ▫ May lead to permanent brain damage ▪ Ocular ▫ Visual impairment

Chapter 64 Coccobacilli: Facultative Anaerobes SIGNS & SYMPTOMS ▪ Range from asymptomatic to severe illness ▪ Onset of symptoms can be acute/insidious ▪ Incubation ▫ 1–4 weeks to several months ▪ Acute generalized infection ▫ Acute undulating fever (key sign), arthralgia, myalgia, fatigue, headache, night sweats, malaise, weight loss ▫ Hepatomegaly, splenomegaly, lymphadenopathy ▫ Foul-smelling perspiration (characteristic sign) ▪ Localized infection ▫ Symptoms depend on organ/organ system affected DIAGNOSIS LAB RESULTS ▪ Rising titers of specific antibodies ▫ Initial rise in IgM class titers, followed in several weeks by predominance of IgG antibodies; both decrease over time with treatment ▪ Anemia, thrombocytopenia Microbe identification ▪ Positive bodily fluids/tissue culture ▪ Serum agglutination, enzyme-linked immunosorbent assay (ELISA) ▪ Polymerase chain reaction (PCR) ▪ Lysis-centrifugation technique OTHER DIAGNOSTICS ▪ History of travel, food consumption, occupation TREATMENT MEDICATIONS ▪ Six-week course of doxycycline plus streptomycin/gentamicin/doxycycline plus rifampin ▪ In children < eight years old ▫ Trimethoprim-sulfamethoxazole (TMPSMX) plus rifampin SURGERY ▪ Surgical interventions sometimes necessary for osteoarticular manifestations (e.g. pyogenic joint effusions), hepatosplenic granulomas/abscesses, cardiac complications (e.g. valve replacement surgery) OTHER INTERVENTIONS ▪ Prophylaxis ▫ Biosafety level 3 in laboratories recommended while handling Brucella cultures ▫ No vaccines for humans; live attenuated vaccines containing strains of B. abortus, B. melitensis used for animals OSMOSIS.ORG 351

HAEMOPHILUS DUCREYI osms.it/haemophilus-ducreyi PATHOLOGY & CAUSES ▪ Virulence factors ▫ Lipooligosaccharide ▫ Pili: provides attachment of bacteria ▫ Soluble cytolethal distending toxin, cytotoxic hemolysin, hemoglobinbinding protein, copper-zinc superoxide dismutase, filamentous hemagglutininlike protein, zinc-binding periplasmic protein ▪ Culture ▫ Isolation specimen: genital ulcer swab, lymph node aspirate ▫ Media: enriched growth medium contains factor X (hemin), serum incubated at 33–35ºC/91.4–95°F with CO2; small, heterogenous, gray/ translucent colonies ▪ Causative agent of sexually transmitted genital ulcer called chancroid (AKA ulcus molle), associated inguinal lymphadenopathy ▪ Some strains causes cutaneous ulcers in children in South Pacific, parts of equatorial Africa Transmission ▪ Sexual intercourse (genital ulcers) ▪ Nonsexual transmission (cutaneous ulcers) Pathogenesis ▪ Incubation ▫ 4–10 days ▪ Inoculation through epidermal microabrasions → attachment of bacteria to extracellular matrix in skin via pili, 352 OSMOSIS.ORG lipooligosaccharide → attachment to cells via specific heat shock protein (GroEL) → cytotoxin release, epithelial injury → formation of erythematous papule → evolves into pustule → pustule ruptures, forms ulcer RISK FACTORS ▪ Uncircumcised individuals, poverty, multiple sexual partners COMPLICATIONS ▪ Increases risk for HIV contraction SIGNS & SYMPTOMS ▪ Single/multiple painful genital ulcers on erythematous base, 1–2cm/0.39–0.79in diameter with sharply demarcated borders; base of ulcer covered with purulent exudate, bleeds easily when scraped ▪ Predilection sites ▫ Prepuce, coronal sulcus, glans penis in individuals who are biologically male ▫ Labia, vaginal introitus, perianal area in individuals who are biologically female ▪ Individuals who are biologically female ▫ Dysuria, dyspareunia, vaginal discharge, rectal bleeding, painful defecation ▪ Inguinal lymphadenopathy in approx. 50% of cases (more common in individuals who are biologically male) ▫ Painful fluctuant buboes (swollen lymph nodes); if untreated, may spontaneously rupture, form draining sinus, releases pus

Chapter 64 Coccobacilli: Facultative Anaerobes DIAGNOSIS LAB RESULTS Microbe identification ▪ Diagnosis of confirmed chancroid ▫ Culture (not widely available) ▪ Nucleic acid amplification tests ▫ Not available outside of clinical research purposes ▪ Polymerase chain reaction (PCR) multiplex ▫ Detection of bacterial DNA ▪ Histologic characteristics of chancroid OTHER DIAGNOSTICS ▪ Diagnostic criteria for probable chancroid ▫ ≥ one painful genital ulcers ▫ No evidence of Treponema pallidum infection (by darkfield microscopy/ serologic testing) ▫ No evidence of Herpes simplex virus (HSV) infection ▫ Appearance of genital ulcers, regional lymphadenopathy ▪ Purulent exudate in superficial epidermis with perivascular, interstitial mononuclear infiltrate in dermis Figure 64.1 An ulcer on the glans penis of a male with chancroid. The ulcer is typically painful, unlike the ulcer of primary syphilis. TREATMENT MEDICATIONS ▪ Single-dose therapy with azithromycin/ ceftriaxone ▪ Alternative ▫ Multiple-dose therapy with ciprofloxacin/erythromycin OTHER INTERVENTIONS ▪ Fluctuant lymphadenopathy ▫ Needle aspiration, drainage to prevent spontaneous rupture OSMOSIS.ORG 353

HAEMOPHILUS INFLUENZAE osms.it/haemophilus-influenzae PATHOLOGY & CAUSES ▪ Haemophilus: blood loving ▪ Characteristics ▫ Catalase, oxidase positive ▪ Virulence factors ▫ Polysaccharide capsule: prevents phagocytosis; causes ciliostasis, evades mucociliary clearance of bacteria; classified into six serotypes based on capsular antigens (A, B, C, D, E, F); some strains unencapsulated (AKA nontypable); most clinical isolates Haemophilus influenzae type B (Hib)/ nontypable ▫ IgA1 protease, adherence factors, antigenic variation, biofilm formation ▪ Gram stain of exudate shows bacteria arranged in chains (“school of fish”) ▪ Culture ▫ Isolation specimen: cerebrospinal fluid (CSF), urine, serum, synovial fluid ▫ Media: chocolate agar/Fildes medium (hemolyzed erythrocytes) with factor X (hemin), V (nicotinamide adenine dinucleotide) supplementation in aerobic, only factor X supplementation in anaerobic environment ▫ Convex, smooth, grey/transparent colonies ▪ Gram-negative coccobacillus → meningitis, respiratory tract infections ▪ Nontypeable strains colonize nasopharynx of 40–80% children, adults ▪ Hib colonizes 3–5% children TYPES Hib ▪ Epiglottitis in older children, adults ▪ Cellulitis (most common in young children) ▪ Pneumonia ▫ Sometimes with meningitis, epiglottitis ▪ Meningitis, septic arthritis, osteomyelitis 354 OSMOSIS.ORG Nontypable ▪ Less invasive due to lack of capsule; causes mild localized respiratory tract disease in children, adults ▪ More severe in immunocompromised/ predisposed individuals ▫ Otitis media, sinusitis, purulent conjunctivitis, bacterial pneumonia in children (in low-income countries), neonatal bacteremia ▫ Community-acquired pneumonia in adults with underlying lung disease ▫ Exacerbation of chronic obstructive pulmonary disease (COPD) ▫ Meningitis in individuals with predisposition/conditions causing leakage of CSF fluid (e.g. sinusitis, otitis media, head trauma) Transmission ▪ Direct contact with respiratory tract secretions/airborne respiratory droplets Pathogenesis ▪ Inoculation → passage through upper respiratory tract → adherence to respiratory epithelium, LPS inhibits mucociliary clearance → colonization spreads throughout respiratory tract → sinuses, otitis, pneumonia ▪ IgA1 protease, antigenic variation, paracytosis, biofilm formation → perseverance of bacteria RISK FACTORS ▪ Viral infection, sickle-cell disease, asplenia, HIV infection, malignancies, congenital deficiencies of complement components COMPLICATIONS ▪ Nontypable in neonates, immunocompromised individuals → septicemia, meningitis, septic arthritis ▪ Hib meningitis → subdural effusion/ empyema; ischemic/hemorrhagic cortical

Chapter 64 Coccobacilli: Facultative Anaerobes infarction; cerebritis (nonviral parenchymal infection of brain); ventriculitis; intracerebral abscess; hydrocephalus; neurologic sequelae (e.g. permanent sensorineural hearing loss, seizures, intellectual disability) ▪ Hib pneumonia can spread to pericardium → purulent pericarditis SIGNS & SYMPTOMS Hib ▪ Meningitis ▫ Fever, lethargy, irritability, vomiting, altered mental status ▫ Fulminant course → rapid neurologic deterioration, respiratory arrest ▫ Positive Kernig’s sign: inability to straighten leg when hip flexed to 90º ▫ Positive Brudzinski’s sign: flexing of neck by examiner → flexing of hips, knees ▪ Epiglottitis ▫ Fever, sore throat, difficulty speaking, dyspnea → severe stridor, dysphagia, pooling of secretions, drooling ▫ “Tripod” posture: individual takes sitting position with trunk leaning forward, neck hyperextended, chin thrust forward to get more air through obstructed airway ▪ Cellulitis ▫ Fever; warm, tender area of erythema/ violaceous discoloration on cheek/ periorbital area ▪ Septic arthritis ▫ Fever, pain, swelling, tenderness, decreased mobility of affected joint Nontypeable ▪ Otitis media ▫ Fever, ear pain, irritability, sleep disturbance, otorrhea ▫ Red bulging tympanic membrane with decreased mobility upon pneumatic otoscopy examination ▫ Often conjoined with conjunctivitis ▪ Sinusitis ▫ Fever, persistent purulent nasal discharge or cough > 10 days ▫ Tenderness over involved paranasal sinuses DIAGNOSIS DIAGNOSTIC IMAGING Laryngoscopy ▪ Red, swollen epiglottis; aryepiglottic folds ▪ Examine with caution; possible laryngeal spasm X-ray ▪ Thumb sign on epiglottis (radiographic corollary of omega sign) LAB RESULTS Microbe identification ▪ Positive Gram stain, bacterial culture of CSF, synovial fluid, epiglottis, pleural, pericardial, other sterile fluids ▪ Latex agglutination, enzyme immunoassay, coagglutination ▫ Type B capsular antigen detection in CSF, serum, urine ▪ Definitive diagnosis ▫ Culture of fluid obtained by sinus aspiration, tympanocentesis, tracheal/ lung aspiration, bronchoscopy, bronchoalveolar lavage Figure 64.2 An X-ray image of the chest demonstrating diffuse airway shadows in an individual with bronchopneumonia. H. influenzae is a causative organism of bronchopneumonia. OSMOSIS.ORG 355

TREATMENT MEDICATIONS Prevention ▪ Conjugate Hib vaccines ▫ Routine vaccination of infants of two months ▪ Rifampin chemoprophylaxis ▫ Individuals in close contact with infected; incompletely vaccinated individuals in households with infants/ children < four years old Hib with meningitis ▪ Third generation cephalosporins ▫ Adults: ceftriaxone ▫ Children: ceftriaxone plus dexamethasone (decreases immune response to released LPS upon bacterial death, lowers chance for destruction of neurons, neurologic sequelae) ▪ Epiglottitis (life-threatening condition; prompt treatment paramount) ▫ Ceftriaxone Nontypable ▪ Amoxicillin/clavulanate, broad-spectrum cephalosporins, macrolides (azithromycin/ clarithromycin), fluoroquinolones SURGERY ▪ Epiglottitis ▫ Placement of artificial airway PASTEURELLA MULTOCIDA osms.it/pasteurella-multocida PATHOLOGY & CAUSES ▪ Characteristics ▫ Zoonotic infection (e.g. birds, cats, dogs, rabbits, cattle, pigs); oxidase, catalase, nitrate reduction positive ▪ Virulence factors ▫ Polysaccharide capsule: prevents phagocytosis; divided into serogroups based on capsular antigens (A, B, C, D, E) ▫ Lipopolysaccharide: endotoxin ▫ Sialidases, hyaluronidase, surface adhesins, iron acquisition proteins, pasteurella multocida toxin (PMT) ▪ Culture ▫ Isolation specimen: respiratory tract samples, CSF ▫ Media: sheep blood, chocolate, HS, Mueller–Hinton agar at 37ºC/98.6F; opaque/gray colonies 1–2mm in diameter ▪ Medically important subspecies ▫ P. multocida subsp multocida, P. 356 OSMOSIS.ORG multocida subsp septica, P. multocida subsp gallicida Transmission ▪ Most commonly cat/dog bites, scratches, licks TYPES ▪ Soft tissue infections ▫ Cellulitis at site of inoculation (most common) → abscess, necrotizing soft tissue infections, septic arthritis, osteomyelitis ▪ Respiratory infections ▫ Due to underlying chronic pulmonary disease; glossitis, pharyngitis, sinusitis, otitis media, epiglottitis, tracheobronchitis, pneumonia, empyema, lung abscess ▪ Invasive infection (immunocompromised, infants) ▫ Bacteremia, meningitis, intra-abdominal infections (peritonitis, appendicitis), endocarditis, septic arthritis, ocular infection

Chapter 64 Coccobacilli: Facultative Anaerobes Pathogenesis ▪ Inoculation → attachment of bacteria to ECM, cells soft tissue → PMT secretion → tissue inflammation within 24 hours LAB RESULTS COMPLICATIONS Microbe identification ▪ Culture, PCR, serological testing ▪ Sepsis, septic shock SIGNS & SYMPTOMS ▪ Soft tissue infections ▫ Wound inflammation, cellulitis with purulent drainage; regional lymphadenopathy ▪ Respiratory tract infections ▫ Fever, malaise, dyspnea, pleuritic chest pain ▪ Sepsis ▫ Purpura fulminans (rash rapidly progresses from petechiae, purpura to gangrene/limb amputation) ▪ Respiratory infection ▫ Wheezing, rhonchi, dullness DIAGNOSIS OTHER DIAGNOSTICS ▪ History of animal contact ▫ Cat bites pose higher risk for developing osteomyelitis, septic arthritis TREATMENT MEDICATIONS ▪ ▪ ▪ ▪ Penicillins Tetracyclines Cephalosporins Quinolones OSMOSIS.ORG 357