Bacterial Infections(Part 1) Ma. Anna P. Bañez, M.D. Department of Child Health Staphylococcus • Classified – Coagulase positive • Staphylococcus aureus Staphylocccus aureus • Virulence Factors – Cell wall Components • Peptidoglycan • Teichoic acid • Slime (coagulase- negative) • Capsule – Toxins • Catalase • Coagulase • Leukocidin – Enzymes • Enterotoxins A, B,C,D, E • Exfoliatin A,B • TSST-1 Clumping factor Fibronectin binding PBP2a Protein A Hemolysin Lipase ß- Lactamases – Coagulase negative • Staphylococcus epidermidis, S. saprophyticus, S. haemolyticus Relationship of Virulence Factors to diseases associated with S. aureus Staphylococcus aureus Multiple strains Localizing Strain TSST 1 Coagulase Clumping factor Bacteremia Protein A TSS Food poisoning SSS Toxin Producing Strains enterotoxin exfoliatin Epidemiology • Most neonates are colonized within the 1st week of life • 20-30% of normal individuals are colonized with S. aureus in the anterior nares • Other sites of colonization: axilla,perineum,vagina ,rectum • Transmission: direct contact or droplet spread • Handwashing between patients contacts decreases the transmisssion Focal Infection Disseminated Infection Boil Abscess Sinusitis 1 | Bacte-Pedia Epidemiology • Factors that increase the likelihood of infection – defects in mucocutaneous barriers – congenital or acquired defects in complement,phagocytosis,chemotaxis (Job,ChediakHigashi,Wiskott-Aldrich) --corticosteroid treatment – acidosis – azotemia – viral Infections ( measles, influenza) Clinical Manifestations Staphylococcal Scalded Skin Syndrome • Secondary to exfoliative toxins A&B • Affects infants and children <10 y/o • Rash preceded by malaise,fever, irritability,exquisite skin tenderness • (+)brightly erythematous skin become wrinkled;if severe,(+) generalized ,sterile, flaccid bullae->large sheets of epidermidis peel away->moist,glistening denuded areas->dry quickly & heal by desquamation w/in 2-3days • Prominent radial crusting and fissuring around eyes,mouth and nose Staphylococcal Scalded Skin Syndrome Abortive type: (+)generalized scarlatiniform rash w/o blister w/ facial crusting and fissuring Ritter Disease: generalized exfoliation in the newborn Bullous Impetigo: localized type of SSSS Staphylococcal Scalded Skin Syndrome Diagnosis: Clinical Skin biopsy: site of blister cleavage is granular layer Culture:>90%(+) culture np <10%(+) culture skin/blood Treatment: anti-staphylococcal antibiotic 2 | Bacte-Pedia Toxic Shock Syndrome Secondary to TSST-1 that causes massive fluid loss from IV space directly or thru IL-1 & TNF Epidemiology: Patients at risk: -menstruating women using vaginal tampons/other vaginal devices -non-menstrual cases:infected wound, nasal packings,sinusitis,tracheitis,pneumonia,abscess, burns,etc Staphylococcal Toxic Shock Syndrome Clinical manifestations • Abrupt onset w/ high fever,vomiting & diarrhea,sorethroat,headache,myalgias • Diffuse macular rash appears w/in 24 hrs,w/ strawberry tongue,hyperemia of pharyngeal,conjunctival & vaginal mucosa • (+)altered sensorium,oliguria,hypotension->shock ,DIC,ARDS, heart/renal failure • Recovery w/in 7-10days w/ desquamation of palm/soles; hair/nail loss after 1-2 months Diagnostic Criteria of Staphylococcal TSS Major Criteria (All Required) •Acute fever, temp >38.8 •Hypotension (orthostatic or Shock) •Rash (erythroderma with late desquamation) Minor Criteria (Any 3) •Mucous membrane inflammation •Vomiting, diarrhea •Liver abnormalities •Renal abnormalities •Muscle abnormalities •CNS abnormalities •Thrombocytopenia Diagnosis • Based on clinical manifestations • No specific laboratory tests; appropriate selective tests show multi- organ system involvement • Bacterial culture of the associated focus (vagina, abscess) Exclusionary Criteria •Absence of another explanation •Negative blood CS (except for S. aureus) Treatment • B-lactamase resistant anti-staph +/clindamycin (unresponsive cases) • Drainage of the vagina, removal of retained tampons and focally infected site • Fluid treatment • Steroids & IVIg for severe cases Staphylococcal Food Poisoning • Secondary to Enterotoxin • Epidemiology: -ingestion of toxin-contaminated food:pastries custards, salad dressing, sandwich, poultry, sliced meat/meat products -involve uncooked food in contact w/ food handler’s hand or inadequately heated/refrigerated food. -food left in room temperature permit multiplication of organism and release of pre-formed, heat stable toxin 3 | Bacte-Pedia Staphylococcal Food Poisoning Clinical Manifestations -incubation period: 30 minutes-8 hrs(2-4 hrs) -abrupt onset of severe nausea, abdominal cramps, vomiting & prostration-> watery diarrhea -normal to low grade fever -last only 1-2 days Diagnosis: -epidemiologic considerations -isolation from stool/vomitus, toxin-testing Treatment: Fluid and electrolyte replacement Clinical Manifestation • Skin infections: S.aureus the most common cause of pyogenic skin infection A. Impetigo -non-bullous -bullous impetigo:always caused by S.aureus B. Folliculitis C. Hydradenitis D. Furuncles F. Carbuncles G. Cellulitis: suppurative; may appear late or prevented by early tx; maybe external manifestations of underlying bone/joint infection H. Breast abcess -Wound infection -Tropical pyomyositis: subacute ,not septic , muscle pain,single or multiple Clinical manifestations • Eye Infection • Purulent conjunctivitis • Hordeolum or Stye –Involve sebaceuos gland/ eyelash follicles –Well localized or w/ eyelid cellulitis • Pre-septal /Orbital cellulitis • Cavernous sinus thrombophlebitis –2/3 of cases due to S.aureus –Periorbital swelling and inflammation + CN paralysis (III,IV,VI), proptosis, retinal venous obstruction,aute visual deteriotation 4 | Bacte-Pedia Clinical Manifestations Sepsis -bacteremia& sepsis may be associated w/ any localized infection -maybe acute w/fever, chills, nausea,vomiting, myalgia -unrecognized until w/ secondary hematogenously disseminated focus(lungs,heart,joint/bones,brain) Clinical Manifestations Purulent Pericarditis -Rare, serious complication after bacteremia -Usually with associated illness(respiratory tract/bone/skin infection) -S.Aureus,most common followed by hib, meningococci,pneumococci,gram(-) enterics -Fever,respiratory distress,chf -(+/-) Pericardial friction rub -Diagnosis: CXR (cardiomegaly), 2d echo -Treatment: pericardiocentesis,pericardiectomy Clinical manifestations Endocarditis -Occur in patients w/ no heart disease, w/ congenital or rheumatic lesions,after cardiac surgery -S. aureus,common cause of acute, virulent endocarditis on native valves -Fever, lethargy w/ rapid disease progression -Frequent cardiac decompensation -Serious symptoms & rapid progression recognized early before embolic phenomena /chronic changes occur(anemia,splenomegaly,splinter/conjunctival hemmorhage & janeway spots) -Diagnosis: blood CS, 2d-echo Clinical Manifestations -Osteomyelitis -Primarily caused by S.Aureus -By hematogenous route or contiguous focus -Infants: minimal toxicity;no localsigns,pseudo- paralysis, multiple -Older children: either acutely w/ fever & toxicity or subacutely w/ local complaints -PPE: marked tenderness over involved bone; (+) local swelling/redness when infection spread out from metaphysis to subperiosteal space causing secondary soft tissue infection -Diagnosis: Blood culture (+) 50-57% of cases Needle aspirate of bone pus: best specimen Bone x-ray: destructive changes seen in 10-16 days radionuclide scan/MRI ESR, CRP & WBC count monitor course & response Clinical manifestations Septic arthritis Common pathogens according to age: Neonate: S.Aureus 2 months-4 years old: hib, S.Aureus Beyond 4 years old: S.Aureus -Maybe hematogenous, by contiguous spread or direct inoculation -PPE: redness,swelling skin/soft tissue + painful joint w/ decrease range in motion -Diagnosis: Blood culture Need aspirate of joint fluid: best specimen X-ray: joint space widening & soft tissue swelling ESR, CRP & WBC count monitor course & response to TX Clinical Manifestations Deep Tissue Abscesses -in the course of bacteremia, staphylococci may establish multiple, metastatic foci: Liver abscess: - S.aureus, gram (-) enterics & anaerobes are the most common isolates -fever, abdominal pain & hepatomegaly -Diagnosis: ultrasound Renal Abscess: -S. aureus most common -fever,costovertebral pain & tenderness Splenic Abscess: -polymicrobial : S. aureus, Streptococci,Enterobacteriaciae 5 | Bacte-Pedia Clinical Manifestations Staphylococcal Enterocolitis -follow overgrowth of normal flora by staphylococcus after use of broadspectrum antibiotics -bloody, mucoid diarrhea Staphylococcal Peritonitis -in patients w/ CAPD -catheter tunnel usually involved Meningitis -S. aureus, unusual cause -occurs in patients w/ cns abnormalities/head trauma DIAGNOSIS: presumptive: gram(+) cocci in grapelike clusters definitve: isolation by culture Treatment: -Incision and drainage -Removal of foreign bodies -Antibiotics Serious infections: -Intravenous therapy: B-lactamase resistant b-lactam: oxacillin -Other drugs: First/second generation cephalosporins B-lactam/b-lactamase inhibitor, clindamycin(except endocarditis,cns infections) - Strains resistant to BLR b-lactam ab(mrsa/ ORSA) vancomycin - Rifampicin or gentamycin provide synergism if combined w/ BLR b-lactam Treatment Skin and Soft Tissue infections -oral: BLR B-lactam(cloxacillin) first/second gen cephalosporins B-lactam/B-lactamase inhibitor Clindamycin Erythromycin Co-trimoxazole -localized/superficial infections topical mupirocin,fusidic acid Prevention Handwashing is the most effective measure for preventing the spread of staphylococci from one individual to another Coagulase – Negative Staphylococci - normal inhabitants of human skin,throat, mouth,vagina & urethra Staphylococcus epidermidis -most common & persistent species -infection preceded by colonization or direct inoculation during surgery -produces an exopolysaccharide (slime) that enhances adhesion to foreign surfaces,resist phagocytosis & impair penetration to foreign surfaces -originally avirulent, now a nosocomial pathogen: - in patients with indwelling foreign devices -surgical trauma -immunocompromised states( malignancy, neonates) -Low virulence usually requires presence of another factor (immune compromised state /foreign body) for development of infection 6 | Bacte-Pedia Clinical Manifestations Bacteremia - indolent, not associated with overwhelming shoc - S. epidermidis , the most common cause of late-onset sepsis among prematures & nosocomial bacteremia in all ages - also in patient w/ malignancy and bone marrow transplantation Endocarditis -infection of native heart valves w/ or w/out CV catheter -S.epidermidis, a common cause of prosthetic valve endocarditis Central Venous Catheter Infection -exit site & subcutaneous tunnel become infected->direct path to bloodsream -common due to high rate of colonization -line sepsis: fever, tenderness/erythema at exit or along tunnel, catheter thromboses, leucocytosis Clinical Manifestations CSF Shunt Infection -S. eidermidis ,common pathogen in CSF shunt meningitis -usually introduced during surgery -70-80% within 2 months of operation: meningeal irritation, fever, increased ICP &/or peritonitis UTI: -S.eidermidis causes asymptomatic UTI among catheterized pts.,after renal surgery/transplant -S.saprophyticus causes symptomatic UTI in previously healthy sexually active teenage girls Peritonitis: -S.epidermidis, most common pathogen in CAPD_associated peritonitis -abdominal pain,fever, >100 wbc/mm3, (+) gs/culture Diagnosis True bacteremia should be suspected; – when blood cs grow rapidly CONS (1st 24 hours) – 2 or more blood culture is positive with the same CONS – When the peripheral venous blood CS has quantitative colony count comparable to that drawn from central venous catheter – when clinical and laboratory S and S compatible with CONS sepsis are present and subsequently resolve with appropriate therapy No blood CS that is positive for CONS in a neonate or patient with IV catheter should be considered contaminated without careful assessment and examination of patient Treatment -BLR B-lactam antibiotic (Oxacillin) -for MRSE or ORSE: Vancomycin -addition of gentamicin or rifampicin may increase antimicrobial efficacy -removal of foreign bodies (CSF shunt, prosthetic heart valves) Clinical Manifestations 7 | Bacte-Pedia Streptococcal Pharyngitis -GABS,major cause of bacterial pharyngitis -Highest in children > 3y/o (5-15 y/o) -Fever,headache,abdominal pain,vomiting -Sorethroat soon after initial complaint; slight to severe -(+) Early, tender anterior cervical adenitis -Physical findings suugestive of streptococcal infection: diffuse redness of tonsils /pillars Petechial mottling of soft palate w/ or w/o exudate -Features suggestive of viral infection: ( + 2 or more) Conjunctivitis,rhinitis,cough, hoarseness -Clinical judgement not predictive -Toddlers with GABS respiratory infection: protracted fever w/ fever, irritability,anorexia,seromucoud rhihitis, nasal excoriation Streptococcal Pharyngitis Streptococcal Pharyngitis – Treatment • Early antibiotic therapy will hasten recovery by 12-24 hr • Primary benefit of treatment is prevention of RF (almost successful it given within 9 days of illness) • Reduce transmission of infection to others • Penicillin : drug of choice; 10 day TX – Pen V <60 lbs: 250 2-3x /dy >60 lbs: 500 2-3x/dy – Amoxicillin – benzathine penicillin single IM dose » <27 kg 600,000 U » 1.2 Million U for larger children and adult – Erythromycin estolate / ethyl succinate (allergy to penicillin) » 30-40 mg/kg/day tid or qid – Diagnosis • Throat culture • Serology: rapid, high specificity Scarlet Fever • Uncommon < 3y/o – Caused by pyrogenic exotoxin (erythrogenic toxin) • Acute onset of fever, vomiting,toxicity,chills and pharyngitis followed by rash 12-46 hrs 8 | Bacte-Pedia Vaginitis • Common cause of pre- pubertal vaginitis • Serous discharge with marked erythema and irritation of vulvar area • Dysuria and discomfort in walking 9 | Bacte-Pedia Severe Invasive Disease • Toxic Shock syndrome – occurrence of shock, multiorgan system failure early in the course of infection – (+)soft tissue infection(cellulitis,absc ess,necrotizing fasciitis)w/ increasing pain Hypotension plus two or more Renal Impairment Coagulopathy Hepatic involvement ARDS Scarlet fever rash Soft tissue necrosis Definite case Clinical criteria plus group A streptococcus from a normally sterile site Probable case Clinical criteria plus group A streptococcus from a non strerile site Severe Invasive Disease • Focal and systemic infections that do not meet the criteria for TSS and necrotizing fasciitis – – – – – – – – Meningitis BPN Peritonitis Puerperal sepsis Osteomyelitis Suppurative arthritis Myositis Surgical wound infection Suppurative Complications Secondary to local inflammation: peritonsillar abscess retropharyngeal abscess Direct extension: otitis media sinusitis Lymphatic spread: lymphadenitis Bacteremia: sepsis osteomyelitis pneumonia Non-suppurative complications Rheumatic Fever: -associated w/ serotypes M1,2,5,6,18,24 -follows a streptococcal pharyngitis -abnormal host immnue response to an undefined component of GABS->immunologic damage -latent period: 1-3 wks support immunologic tissue damage Glomerulonephritis: -acute nephritic syndrome 1-2 wks after a streptococcal pharyngitis or skin infection -probably immune complex –mediated (depressed C3) 10 | B a c t e - P e d i a Non-suppurative Complications Poststreptococcal Reactive Arthritis: -acute arthritis after a streptococcal pharyngitis but does not fulfill Jones criteria -unknown whether a distinct syndrome or a manifestation of RF -large joints,non-migratory -latent period :<10 days -doesn’t dramatically respond to aspirin/NSAID -observe for subsequent carditis Non-suppurative Complications Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus pyogenes (PANDAS) -sudden onset of obsessive-compulsive &/or Tic disorders -patients w/ Sydenham’s chorea frequently have obsessivecompulsive symptoms & a subset of patients w/ obsessivecompulsive & tic disorders will have chorea as well as acute exacerbations following grp A streptococcal infection -(+)autoimmune antibodies in response to GAS infection that cross-react w/brain tissue Laboratory Diagnosis Microscopy: gram (+) cocci in pairs/chains Culture: gold standard Antigen detection: EIA or latex agglutination -very specific, low sensitivity -confirm negative test by culture Antibody detection: Antibody to Streptolysin O (ASO) -measured 3-4 wks after infection ->166 Todd units in 80% of untreated streptococcal pharyngitis -modified or abolished by antibiotic Tx -high titers in RF; variable response in AGN -weakly (+) or normal in pyodermas(streptolysin inactivated by skin lipids) Anti-Deoxyribonuclease -best serologic test for strep pyodermas -rise seen 6-8 wks after infection -(+) in streptococcal pharyngitis Nonspecific Findings increased or normal WBC count increased ESR,CRP Treatment Streptococcal Pharyngitis: Phenoxymethyl Pen: 10 day- treatment <60 lb :400,000(250) 2-3x a day >60 lb :800,000(500) 2-3x a day Other Drugs: erythromycin,amoxycillin,cefalexin, clindamycin Severe Streptococcal Infections Pen G Na : 250,000-400,000 u/k/day, in 4-6 doses x 2-6 weeks Streptococcal Impetigo Topicals( bacitracin or mupirocin) Oral antibiotics if with multiple lesions Prevention • Primary Prevention – Appropriate antibiotic therapy instituted before the 9th day of symptoms of acute group A Streptococcal pharyngitis • Secondary Prevention – Prevent group A Streptococcal pharyngitis in patients at substantial risk of recurrent acute RF Secondary Prevention of RF Group B Streptococcus ( Streptococcus agalactiae) Dose 1.2 M u Frequen cy Every 34 weeks Route Antibiotic IM Benzathine Pen G • Major cause of neonatal bacterial sepsis • Facultative anaerobic gram positive cocci form chain or diplococci • 9 serotypes Ia,Ib,II,III,IV,V,VI,VII, VIII Oral Pen V Sulfadiazine Erythromycin 250 mg BID 500-1000mg OD 250 mg BID 11 | B a c t e - P e d i a Group B Streptococcus ( Streptococcus agalactiae) • Vaginal or rectal colonization occurs in approx 30% of pregnant women ( usual source for GBS transmission infants) • Risk for early onset sepsis – – – – Prolonged rupture of membrane >18 hours Intrapartum fever Prematurity(<37 wks) Maternal bacteremia during pregnancy Clinical manifestations Parturient mother: • -GBS a major cause of: endometritis amnionitis UTI Clinical manifestations Newborns – infants </= 3 months Early Onset infection -occurs from 0-6 days -ranges from asymptomatic bacteremia to septic shock -in-utero infection may result in fetal asphyxia, coma ,shock -w/ prominent respiratory symptoms: tachypnea,apnea,grunting,retractions,cyanosis CXR findings: reticulogranular pattern 50% patchy pneumonia 30% pleural effusion,pulmonary edema,cardiomegaly,increased pulmonary markings -Bacteremia or sepsis w/out localization 30-40% -Meningitis (10%) Clinical manifestations Late onset infections -bacteremia without focus 55% -meningitis 35% -osteoarthritis -soft tissue infections Presenting signs: fever , lethargy Group B Streptococcus ( Streptococcus agalactiae) Diagnosis : Presumptive: gram stain: gram(+) cocci latex agglutination:detection of GBS in serum, csf or urine Definite: isolation of GBS from blood/sterile fluids Group B Streptococcus ( Streptococcus agalactiae) • Treatment – Penicillin is the drug of choice – 450,000-500,000 U/kg/24 hr – Ampicillin 300-400 mg/kg/24 hour Treatment Bacteremia without a focus meningits ventriculitis osteomyelitis Duration 10 days 2-3 weeks 4 wks 4 wks 12 | B a c t e - P e d i a Prevention Selective intrapartum chemoprophylaxis -decreased incidence of early onset disease -Pen G or Ampicillin given immediately to selected women at onset of labor or PROM is anticipated -maternal chorioamnionitis: important indication -all infants whose mothers received SIC should be observed for 48 hrs for signs of infection; diagnostic evaluation and treatment for symptomatic infants Other B-hemolytic Streptococci • Lancefield groups C-H, K-V • Groups C & G most frequent cause of human infections • Colonize intact body surfaces( pharynx, skin, GIT, GUT) • Wound infections, puerperal sepsis, cellulitis, sinusitis,endocarditis, brain abscess, sepsis, nosocomial infections,opportunistic infections Enterococcus -Normal inhabitants of the GIT of humans & animals -oral secretions & dental plaque, upper respiratory tract, skin & vagina may also be colonized -E.faecalis, predominant organism -Risk Factors: breakdown of normal physical barriers (GIT,skin, UT) prolonged hospitalization intravascular catheters prior use of antibiotics compromised immunity Clinical Manifestations • Neonatal Infections – 15% of all neonatal bacteremia and septicemia – Early onset sepsis (< 7 days) mimic early onset GBS infection in healthy FT babies, milder – Late onset infection( >/= 7 days) Risk Factors • • • • Extreme prematurity IV catheter NEC Follows intra-abdominal surgical procedure – Meningitis Clinical Manifestations • Infection in older children – 15% of nosocomial UTI in children and adult – Intraabdominal infections following intestinal perforation and surgery – nosocomial bacteremia and endocarditis, less common in children than in adults Treatment Immunocompetent with localized infection -ampicillin alone Invasive infection sepsis, meningitis and endocarditis -Penicillin/Ampicillin + aminoglycoside -Vancomycin + aminoglycoside if with allergy to penicillin Vancomycin-resistant Enterococcus - Linezolid, Quinupristin-dalfopristin 13 | B a c t e - P e d i a Alpha- hemolytic Streptococcus • S. bovis, S.mitis, S.mutans, S.sanguis • Normal flora of the pharynx,nose,skin, GUT • Common human diseases: dental caries,subacute endocarditis, human bite infections, suppurative intra-abdominal infections Epidemiology • Before the advent of effective conjugate vaccine (1988), Hib responsible for >95% of invasive diseases in children • 90% occurred in children <5y/o; majority in <2y/o • Incidence presently varies in different populations,countries • From 1989-1997, incidence of Hib disease in children <5 yrs, in the US declined by 99% • Non-typable strains: common etiologic agents of otitis media, sinusitis,chronic bronchitis in adults, invasive disease in neonates & immunocompromised children Epidemiology • Increased incidence of invasive disease: Alaskan eskimos, Apaches, Navajos & blacks • Mode of transmission: droplet • Attack rate for secondary Hib cases in household contacts <24 months: 3.2% >47 months: <0.2% Clinical Manifestations Meningitis -clinically indistinguishable to meningitis due to S.pneumoniae or N.meningitides -maybe complicated by other foci of infection(lungs, joints, bones or pericardium) Pneumonia -signs and symtoms indistinguishable from pneumonia due to other organisms -Hib & S.pneumonia, the most frequent isolates from lung aspirate/ blood in children 2 months5 y/o w/ bacterial pneumonia(WHO) Clinical manifestations Acute epiglottitis -Acute onset; (+) sorethroat->rapidly progressive respiratory distress(hoarseness,stridor, irritability, restlessness)->complete obstruction->death -patient insists on sitting, leaning forward w/ extended neck to maximize airway -laryngoscopy:large,swollen cherry red epiglottis -warrants emergency intubation/tracheostomy Septic Arthritis -s/sx indistinguishable from those due to other organism -most common cause among children 2months- 5y/o 14 | B a c t e - P e d i a Clinical Manifestations • Cellulitis – Often have antecedent URTI – No history of trauma – Represent seeding to the involved soft tissues during bacteremia - most common sites of involvement:head &neck especially cheek & preseptal region – Buccal cellulitis: erythematous with a violaceous hue – Preseptal or orbital cellulitis -clinically indistinguishable from other causative agents: S.pneumoniae, S.aureus, GAS _S. aureus or GAS more likely if w/ skin breaks & no fever Clinical Manifestations Pericarditis Occult Bacteremia -bacteremia w/o a focus in 3 months-3 y/o -non-toxix looking -risk factors: temperature >/=39 C WBC ct:>/=15,000 cells -Hib accounts for 5% of cases(10-25% prevaccine era) -risk of subsequent meningitis: 10-15% Clinical Manifestations of Non-typable H.influenzae Otitis media/Sinusitis -Non-typable H.influenzae are common pathogens together with S.pneumoniae and M. catarrhalis -drug of choice: oral ampxycillin Conjunctivitis -non-typable H.influenzae, S.pneumoniae & S.aureus are important pathogens beyond neonatal period Invasive Disease in neonates -occur in association with maternal chorioamnionitis or PROM -include bacteremia with sepsis, pneumonia,RDS with shock, conjunctivitis, scalp abscess, cellulitis, meningitis Diagnosis • Culture: blood, CSF, synovial and pleural fluid and middle ear aspirates • Gram stain:gram(-) coccobacillus presumptive diagnosis • Latex particle agglutination of csf: detection of type b capsular antigen • • • • Treatment B-lactamase-producing H.influnzae isolates identified in 1974 US: 36.5% isolates beta-lactamase-producing Philippines: <5% isolates beta-lactamse producing Hib Meningitis/Invasive Diseases Ampicillin Chloramphenicol 3rd gen cephalosporin:Ceftriaxone/Cefotaxime Non-invasive Diseases Amoxycillin alternative drugs:2nd or 3rd gen cephalosporin,beta-lactambeta lactamse inhibitor,clarithromycin 15 | B a c t e - P e d i a Prevention H. influenza: chemoprophylaxis Vaccine product Total No. of at initiation Doses to be administered HbOC(diptheria CRM 197 protein conjugate) or PRT-T (tetanus toxoid conjugate) PRP-OMP(outer membrane protein,N.meningitides Recommended Regimen 3 doses at 2 mo intervals initially; 4th dose at 12-15 mo of age; any conjugate vaccine for dose 4 2 doses 2 mo apart; 3rd dose at 12-15mo of age; any conjugate vaccine for dose 3 • For all household contacts in the ff circumstances: – Household with at least 1 unimmunized/incompletely immunized contact <4yrs old – Household with a child <12mos old without 1 ºseries – Household with immunocomp. child w/ or w/o immn • For nursery school and child care contacts regardless of age, when 2 or more cases of Hib invasive dse has occurred within 60 days • For index case, if younger than 2 yrs old or member of a household with a susceptible contact & treated with a regimen other than cefo or ceftri, prophylaxis is provided just before discharge 4 3 H. influenza: chemoprophylaxis • Prophylaxis: • rifampicin: 20 mg/kg p.o. once a day for 4 days – maximum dose: 600 mg • Infants younger than 1 month old: dose not established but some experts recommend lowering the dose to 10 mg/kg Serotype distribution of Invasive S.pneumoniae children(2000-Aug.2005) Capeding et al RITM in Filipino 6* 18* 14* 5 9* 20 1 2 4* 19* 38 20% 17% 13.3% 13.3% 10% 10% 3.3% 3.3% 3.3% 3.3% 3.3 *7 valent types=67% 16 | B a c t e - P e d i a Increased incidence and severity in patients w/ the following diseases: • • • • • • • • • • Congenital/acquired humoral immunodeficiency HIV infection Asplenia Nephrotic syndrome Chronic renal failure Organ transplant Diabetes mellitus Chronic pulmonary disease Congestive heart failure Csf leaks Diagnosis • Recovery of S. pneumoniae from site of infection or the blood • Can be identified in body fluids as gram positive lancet shaped diplococci Clinical Manifestations • Most frequent bacterial cause of community-acquired pneumonia, otitis media, sinusitis • With Hib vaccination, pneumococcus & meningococcus have become the 2 most common cause of meningitis in infants and young children • the most common cause of meningitis in the elderly • Account for majority of Occult bacteremia in infants and young children; risk of subsequent meningitis: 1-6% Clinical Manifestations • • • • • • • • • • Peritonitis Laryngotracheobronchitis Osteomyelitis Suppurative arthritis Brain abscess HUS Empyema Pericarditis Mastoiditis Epidural abscess Treatment Penicillin G is the drug of choice for penicillin susceptible strain – Minor infections • oral penicillin v 50-100 mg/kg/24 hr q6-8 hours Prevention • Immunization Purified polysaccharide of 23 pneumococcal serotypes -Poorly immunogenic in children<5 y/o -for children at risk of severe disease PCV7 (conjugate vaccine with 7 serotypes) -4,6B,9V,14,18C,19F,23F -highly recommended for routine immunization starting 6-8 wks of life q 2 months x 3 doses, booster 12-15 months – Bacteremia or BPN • Pen G 200-250,000 u/kg/day q4-6 hour – Meningitis • Pen G 200-300,000 u/kg/day q4-6 hour For serious infections w/ intermediately R strain (MIC 0.1-1mg/L) or highly R strain (MIC>/=2mg/L) – Vancomycin 60 mg/kg/day q6 – Rifampicin maybe added in severe and unresponsive cases 3rd generation cephalosphorins -maybe added or substituted for vancomycin for intermediately R strain Ceftriaxone 100mg/k/day q 12 Cefotaxime 225-300 mg/k/day q 8 17 | B a c t e - P e d i a Prevention • Prophylaxis – Recommended for children with asplenia and sickle cell disease • Phenoxymethyl penicillin – <5 y/o 125 mg BID – >/=5 y/o 250 mg BID Serogroups • 13 • A, B and C most common causes of invasive disease worldwide • A - most common cause of epidemics • B - most common cause of sporadic disease • Y may cause primary pneumonia • Others: D, H, I, K, L, X, Z, W-135, 29E Recent meningococcal disease: Philippines • 1 Oct 2004 to 28 Jan 2005: 98 cases (Baguio City 74, Mt.Province 22, Ifugao 2) • Case fatality ratio 33% • 11 cases laboratory-confirmed Epidemiology -Asymptomatic colonization of the upper respiratory tract is frequent; may lead to immunity -mode of transmission: droplet -risk factors: close contact terminal complement component deficiency(C5-9) properdin deficiency functional/anatomic asplenia -incubation period: 1-10 days (4days) WHO 18 | B a c t e - P e d i a Clinical Presentation *asymtomatic transient bacteremia to fulminant sepsis resulting to death only a few hours after onset Occult bacteremia -N.meningitides account for 1% of cases -non-toxic child w/ fever & (+) blood culture - w/ upper respiratory or GI or maculopapular rash -spontaneously recover or go on to have meningitis -risk of subsequent meningitis: 30-70% Meningococcemia -Abrupt onset with upper respiratory symptoms,fever,chills, myalgia weakness, headache, and a hemorrhagic rash -Skin manifestations develop early: -diffuse mottling to extensive purpura -1st sign to clinical suspicion petechiae 50-60% purpura(microvascular dermal thromboses) 16-24% -seen in fulminant cases(50% mortality) maculopapular 13% no rash 1-2% * presence of hemorrhagic rashes w/ acral distirbution suggestive of meningo or infectious vasculitis -with widespread hematogenous dissemination->rapid progression to septic shock (hypotension,DIC,adrenal hemorrhage, renal/myocrdial failure) 19 | B a c t e - P e d i a Meningitis (w/ or w/ meningococcemia) Uncommon manifestations • • • • • • • Endocarditis Purulent pericarditis Pneumonia Septic arthritis Endopthalmitis Osteomyelitis Chronic meningococcemia • Suspected if with fever, CNS manifestations + hemorrhagic rash • Patients with meningitis have a better prognosis than those with meningococcemia alone - a function of virulence of organism or ability of immune system to contain infection Case Definition (CDC) • Confirmed: isolation of N. meningitidis from a sterile site (e.g. blood, CSF, synovial fluid, pleural fluid, pericardial fluid, petechia or purpura) in a person with clinically compatible illness • Presumptive: gram-negative diplococci from sterile fluid or petechial scraping • Probable: + antigen test in absence of + culture in CSF or purpura fulminans in absence of + blood culture Treatment • Penicillin G IV 250,000 units/kg/day (maximum 12 million units) divided q 4 -6 hrs x 5-7 days ` Alternative drugs: Cefotaxime Ceftriaxone Chloramphenicol Isolation of hospitalized patient • Standard precautions • Droplet precautions till 24 hours after initiation of effective antibiotic therapy • • • • • Prevention Careful observation of exposed people Chemoprophylaxis Meningococcal vaccine Reporting Counseling and public education 20 | B a c t e - P e d i a Chemoprophylaxis Age Rifampin <= 1 mo >1 mo Ceftriaxone <=15 y >15 y Ciprofloxacin >= 18 y Who should receive prophylaxis? High risk contacts Efficacy 72-90% • Household contacts esp. young children • Child care or nursery school contact during 7 days before onset of illness • Direct exposure to index patient’s secretions thru kissing, sharing toothbrushes or utensils during 7 days before onset of illness • Mouth-to-mouth resuscitation; unprotected contact during incubation during 7 days before onset of illness • Frequently slept or ate in same dwelling as index patient during 7 days before onset of illness • Index patient if treated with penicillin; not ceftriaxone Dose Duration 5 mg/kg q 12 hr 2 days 10 mg/kg max 600 mg) q 12 , oral 125 mg IM 250 mg IM 500 mg, oral Single dose 97% Single dose 90-95% Low risk contacts: chemoprophylaxis not recommended • Casual contact: no history of direct exposure to index patient’s oral secretions (school mate or work mate) • Indirect contact: only contact is with high-risk contact • Health care professionals without direct exposure to patients oral secretions In outbreak or cluster, chemoprophylaxis for people other than those at high risk should be administered only after consultation with local health authorities Meningococcal vaccine MPSV4-Tetravalent meningococcal polysaccharide vaccine(A,C,Y,W135) -for high risk children >/=2yo -not routine: infection rate in general population is low, not immunogenic, -adjunct to chemoprophylaxis during outbreaks MCV4-tetravalent meningococcal conjugate vaccine(A,C,Y,W135) -in US, for routine use among adolescents at the 11-12 years old visit Tetanus • Typical situations associated with tetanus: deep puncture wounds,burns,blast injury,iatrogenic cases ear infections,tatooing • Incubation period: 2days to months – In neonates: 5-14 days • Diagnosis is made clinically by excluding other causes of tetanic spasms – Hypocalcemia, phenothiazine reaction, strychnine poisoning, and hysteria 21 | B a c t e - P e d i a Clinical Manifestations Generalized Tetanus A. Neonatal tetanus -secondary to unhygienic delivery & lack of maternal immunization -begin w/in 3-10 day of life -difficulty in sucking/swallowing, excessive crying, decreased movement, stiffness to touch, opisthotonus Generalized tetanus B. Non- neonatal tetanus -progressive increase in stiffness in voluntary muscles:trismus, risus sardonicus, opisthotonus, boardlike abdomen, flexed arms, extended legs, laryngeal spasm -painful spasms precipitated by touch, bright light,noise,etc. -intact sensorium -accumulation of secretions->aspirate -duration of illness: 2 weeks Treatment A.Neutralization of unbound toxin Human Tetanus IG: singlel dose of 500 units, IM for all ages Equine tetanus antitoxin:Anti-tetanus serum(ATS): 10,000 u IM, 10,000 u IV ANST B.Elimination of exotoxin production -Wound Care: clean and debrid -Antibiotic: Metronidazole:30 m/k/dy q6h x 10 days PenG 100,000U/k/dy q4-6h x 10 days Treatment C.Prevention & Control of spasms & convulsion 1.Benzodiazepines Valium: 0.3-0.5 mg/k IV q 2- 4 hrs max: 20-40mkdy Midazolam: 0.05-0.15 m/k/dose IV q 1-2 hrs or infusion 2.Neuromuscular blocking agents: in addition to benzodiazepines for intractable seizures pancuroniun, vencuronium 3.Control of seizures phenobarbital, phenytoin • • • • • • • Supportive management Maintenance of airway Nutrition Fluid & electrolyte balance Good nursing care Rehabilitation Anticipation and prevention of complications During convalescence,active immunization 22 | B a c t e - P e d i a Tetanus prophylaxis in routine wound management History of absorbed TT (doses) Clean, minor wounds Td TIG All other wounds Td TIG Tetanus prophylaxis in routine wound management History of absorbed TT (doses) =3 Clean, minor wounds Td TIG No* no All other wounds Td TIG No+ no < 3 or unknown Yes no Yes Yes If only 3 doses: give a fourth dose *give tetanus toxoid if >/= 10 yrs since last TT-containing vaccine dose +give tetanus toxoid if >/= 5 yrs since last TT-containing vaccine dose Corynebacterium diptheriae • Pathogenesis – Major virulence: (+) 62kd polypeptide EXOTOXIN,> inhibits protein synthesis and causes local tissue necrosis->pseudomembrane -local effect of the toxin: paralysis of palate & hypopharynx -toxin absorption can lead to necrosis of kidney tubules, thrombocytopenia, cardiomyopathy and demyelination of nerves ( occur 2-4 weeks after mucocutaneous infection) 23 | B a c t e - P e d i a Clinical Manifestation • Cutaneous Diphtheria – Indolent, non progressive superficial, ecthymic, non healing ulcer with a gray brown membrane – Extremities are more often affected than the trunk or head – pain, tenderness, erythema and exudate are typical – Respiratory tract colonization, symptomatic infection and toxic complication occur in minority of patients Clinical Manifestation • Infection at other sites – Ear (otitis externa), eye( purulent or ulcerative conjunctivitis), genital tract (purulent and ulcerative vulvovaginitis) – Rare cases of septicemia – Sporadic cases of endocarditis, pyogenic arthritis Complications Cardiomyopathy – Occurs in approx. 10-25% – Responsible for 50-60% of deaths – occurs 2nd to 3rd week of illness but can appear acutely as early as first week or insidiously as late as 6th weeks – Tachycardia out of proportion with fever;s/sx of CHF – ECG changes:prolonged P-R interval, ST-T wave changes, heart blocks, arrythmias – Echocardiogram: dilated/hypertropic cardiomyopathy Complications • Toxic Neuropathy -Parallel the extent of primary infection -multiphasic ; acutely or 2-3 weeks after onset of oropharyngeal inflammation -Hypesthesia and local paralysis of soft palate occur commonly -Weakness of posterior pharyngeal, laryngeal and facial nerves may follow causing a nasal quality in the voice, difficulty in swallowing and risk of death due to aspiration -cranial neuropathy on 5th wk:oculomotor & ciliary paralysis (starbismus,blurred vision,difficultty accomodation) -symmetric polyneuropathy on 10th day-3rd month after infection;primary motor deficiency w/ dec DTRs -clinical & CSF fx indistinguishable to GBS -complete recovery is likely Diagnosis • culture: nose, throat,other mucocutaneous lesions • Portion of the membrane should be removed and submit with underlying exudate Treatment • Antitoxin : mainstay of therapy – Administered as empirical dose 20,000120,000 U based on degree of toxicity, site and size of membrane and duration of illness – Given early, immediately after clinical diagnosis – Not recommended for asymptomatic carriers 24 | B a c t e - P e d i a Treatment Antimicrobial therapy • halt toxin production, treat localized infection, and prevent transmission of the organism to contact Aqueous Penicillin G • 100,000-150,000 u/kg/24 hr divided q5 hr IV or IM Prevention • Asymptomatic Case Contacts – Household contacts and with intimate respiratory or habitual physical contact with patient are closely monitored for illness through the 7 day incubation period – Cultures of the nose, throat and skin lesions are performed – Antimicrobial prophylaxis is given regardless of immunization status • erythromycin 40-50 mg/kg/24 hour qid po x 7 days • Procaine penicillin G 600,000 U IM <30 kg 1.2 U IM for > 30 kg Erythromycin 40-50 mg/kg24 hours q6 PO -Therapy is given for 14 days -Cutaneous diptheria : 7-10 days -Elimination of the organism should be documented by at least two successive cultures from the nose and throat obtained 24 hour apart after completion of therapy -Treatment with erythromycin is repeated if the culture result is positive -respiratory isolation until after cessation of TX – Diptheria toxoid vaccine is given to immunized individual who have not received booster dose within 5 years – Children without booster dose should be vaccinated Prevention • Asymptomatic carriers – Antimicrobial prophylaxis is given for 7 days – Age appropriate preparation of diptheria toxoid is administered immediately if a booster has not been given for 1 year – respiratory isolation or contact isolation until at least two subsequent cultures obtained 24 hour apart after cessation of therapy are negative • Pertussis (intense cough) • Whooping cough Etiologic agents: 1. Bordetella pertussis (95%) 2. Bordetella parapertussis (less frequent) • Etiologic agents of pertussis-like illness: 1. adenoviruses 2. Chlamydia trachomatis 3. Mycoplasma pneumoniae Repeat cultures are performed = 2 weeks after completion of therapy for cases and carriers; - if (+) an additional 10 day course of oral erythromycin should be given and follow up cultures performed Pertussis (intense cough) • Antigenic & Biologically active components of Bordetella pertussis – fimbriae (pili) – filamentous hemagglutinin (FHA) – Pertussis Toxin: subunit A(enzymatically active) & subunit B (binding portion) – Adenylate Cyclase Toxin – Lipo-oligosaccharide (LOS) – Tracheal Cytotoxin – Pertactin Pertussis • highest risk: infants & young children – pertussis in adults – imp’t source of infection in unimmunized or partially immunized children • transmission: droplet – transmissibility is greatest early in the illness during the catarrhal phase • Incubation period: 6-21 days, usually 7-10 days 25 | B a c t e - P e d i a Diagonosis Clinical - suspected if predominant complaint of cough in the absence of: fever,malaise,myalgia,exanthem, enanthem,sorethroat,hoarseness,wheezes,rales - clinical case definition: cough>/= 14 days, w/ a least either paroxysms, whoop or post-tussive vomiting sensitivity:81% specificity:58% - clues in infant<3 months: apnea or cyanosis before appreciation of cough Diagnosis Leucocytosis (15,000-100,00 cells.mm3) - due to absolute lymphocytosis -seen in the catarrhal stage -severe course & death are correlated w/ extreme leucocytosis n thrombocytosis Chest X-ray -perihilar infiltrate or edema(sometimes,butterfly-like) and variable atelectasis -consolidation suggests secondary bacterial infx Diagnosis • Culture of nasopharynx: gold standard • DFA: useful in with previous antibiotics • PCR : not widely available • Antibody detection: not readily available 26 | B a c t e - P e d i a Complications Apnea /bradycardia -secondary to laryngospasm or vagal stimulation before cough, obstruction durind episode, or hypoxemia after episode Secondary infections: Otitis media Bacterial pneumonia: most common cause of death Physical sequelae of forceful coughing: -conjunctival/scleral hemorrhage -petechiae on upper body -epixtaxis -seizures:secondary to hypoxemia, hemorrhage, hyponatremia, alkalosis from vomiting -subcutaneous emphysema -pneumotharax -umbilical /inguinal hernias Treatment Drug of choice: Erythromycin estolate -children: 50 mg/kg q 6h x 14days -abortive or attenuating only if given during pre-paroxysmal stage -reduces communicability at any stage • Alternative agent: – Cotrimoxazole – Newer macrolides: azithro or clarithromycin Prevention Droplet precaution for 5 days after Erythromycin Chemoprophylaxis: -Erythromycin: 40-50mkd po in QID x 14 days -Given to household and close contacts regardless of age or immunization status Active Immunization -80% protective efficacy with household exposure w/ at least 3 doses -whole cell vaccine (DTP) -Acellular vaccine (DTaP) Clinical Manifestations -biphasic course Septicemic phase: - (+) leptospires from blood, csf, pther tissue -initial symptoms last x 2-7 days - may be followed by abrief period of well being Clinical Manifestations -most cases are subclinical or very mild; inapparent infection common in high-risk occupational groups -Symptomatic infection: acute febrile illness w/ nonspecific signs/symptoms: 70& aseptic meningitis: 20% hepatorenal dysfunction: 10% Immune phase: -appearance of antibodies,(-) leptospires from blood, csf, (+) localized signs & symptoms -may persist in kidneys, urine & aqueous humor -lasts for several weeks -typically sudden onset, usually biphasic 27 | B a c t e - P e d i a Clinical manifestations 2 clinical syndromes: 1. Anicteric Leptospirosis -self-limited systemic illness -more common; 85-90% of cases -usually biphasic Clinical manifestations 2 clinical syndromes Anicteric Leptospirosis -Septicemic phase: abrupt, fever,chills, lethargy, severe, debilitating myalgia, extreme muscle tenderness(lower extremities, lumbosacral spine, abdomen), conjunctival suffusion w/photophobia & orbital pain w/o disharge, generalized lymphadenopathy hepatosplenomegaly, truncal rash (maculopapular, urticarial , hemorrhagis, desquamating) -less common:pharyngitis, pneumonitis, athritis, carditis, cholecystitis, orchitis Clinical manifestations 2 clinical syndromes Anicteric Leptospirosis Immune phase: -may follow a brief asymptomatic interlude -characterized by recurrence of fever & aseptic meningitis ; abnormal csf profiles( mod inc in pressures, pleocytosis w/ PMNs,slightly inc protein, normal sugar) in 80% of pts,only 50% w/ meningeal signs,resolve spontaneously w/in a week -uveitis,unilateral or bilateral Clinical manifestations 2 clinical syndromes 2. Icteric leptospirosis -severe form in <10% of patients -septicimic phase similar to anicteric type -immune phase characterized by clinical/laboratory evidence of hepatorenal dysfunction -hepatic manifestations: RUQ pain,hepatomegaly, jaundice, modest increase in liver enzymes -renal manifestations: common, may dominate clinical picture; all w/ renal abnormalities(hematuria, proteinuria,casts),azotemia w/ oliguria/anuria -ARF in 16-40% 0f cases, principal cause of death -hemmorrhage and CV collapse in fulminating cases Diagnosis Serology: -usual basis for diagnosis Microscopic agglutination test -appear by 12th day, maximum at 3rd week -serogroup specific assay, using live antigen suspensions of leptospiral serovar -read by darkfield microscopy for agglutination; titers are determined -definite:(>/=)fourfold rise in titer in paired`sera -probable:single specimen >/=1:1600 Microcapsular agglutination test -utilizes chemically stable microcapsules instead of sheep ethrocytes -detects IgM antibodies -with greater specificity, higher titers and more sensitive in earlier stages <5 days of illness 33% 6-7 days of illness 83% >7 days of illness 96% 28 | B a c t e - P e d i a Treatment ‐initiation of treatment before 7th day will probably shorten clinical course and decrease severity Drug of choice: Pen G Na 6‐8 million U/m2/24 hrs q 4 x 7 days ‐Mild disease: Doxycycline (not for pregnant women and children < 8 yrs old) 10‐20 mg/k/day PO q 6 for 7 day Supportive Management • Fluid and electrolyte blance • Ensure adequate renal perfusion and fluid administration to prevent acute renal failure • (+) pre‐renal azotemia, diuress with fluids or colloids to establish volume • If no response to diuresis wth fluids/ colloids, possible ATN‐> fluid restriction + diuretics & dopamine • With severe prolonged azotemia: dialysis Prevention and Control 1. Hygienic conditions in slaughter houses, farm yards, bathing pools 2. Avoidance of exposure to urine and tissues from infected animals 3. Vaccination of animals 4. Rodent control 5. Chemoprophylaxis Doxycycline: 200 mg 1x a week for people with significant short term exposure in environments w/ risk factors for transmission to humans The End • Lord, thank you for everything, I can’t name them all but it all comes from You, everyday I am very grateful for everything! Edited by: K.D. Espino, 2009 29 | B a c t e - P e d i a