Infections of the upper and lower respiratory tract

Infections of the upper and lower respiratory tract; diagnostics and therapy Spring semester 2007 / 2008 www:szote.u-szeged.hu/clinmicro Case 1 This 2-year-old male child had an upper respiratory tract infection 2 weeks prior to hospital admission. Four days prior to admission, anorexia and lethargy were noted. 3 days prior to admission he was seen in the emergency room because of fever (39.9oC). Physical examination at admission: clear chest, exudative pharyngitis, bilaterally enlarged cervical lymphnodes. A throat culture was taken and a course of penicillin was begun. Case 1 (cont.) The child’s state worsened; he developed respiratory distress on the day of admission. Culture result: no growth of group A streptococci in 24 hours. Next physical examination: yellowish, thick membrane in the posterior pharynx, which bled when scraped and removed, 38.9oC. It turned out that he had received no immunizations. Special isolation medium was used this time for the throat culture. The treatment of the patient begun. Despite appropriate therapy, this child died. Case 1 (cont.) What was the pathogen which grew on this medium? C. diphtheriae gravis on Clauberg agar How frequently should we think of this pathogen in the case of tonsillo-pharyngitis? Causative agents of tonsillo-pharyngitis adeno-, entero-, EBV, CMV, MI, RS (<3 years); influenza, parainfluenza (>3 years); EBV, HSV (young adults) Streptococcus pyogenes ( 5-10 years ) Staphylococcus aureus Haemophilus influenzae b (decreasing due to HIB vaccination) Neisseria gonorrhoeae (young adults) Vincent angina (anaerobes) Corynebacterium diphtheriae Chlamydia pneumoniae ( >5 years ) Mycoplasma pneumoniae (young adults) Yersinia enterocolitica Yeasts (patients with haematological disorders) Viruses: Case 1 (cont.) To cause disease, does this organism invade the bloodstream? How can this organism cause disease? Do all isolates of C. diphtheriae have the potential to cause disease? Case 1 (cont.) What do you know about the epidemiology of diphtheria in different countries? Number of diphtheria cases in the countries of previous Soviet Union between 1965-1995 60000 50000 40000 30000 20000 10000 0 1965 1975 1985 1990 1995 2000 Number of cases Diphtheria in Hungary and in the USA Morbidity (%ooo) Hungary 1930 220 1940 20 1960 3 1970 0.5 USA 1930 90 1970 0.1 Mortality (%) 8 5 4 4 8 5 Case 1 (cont.) What do you know about the epidemiology and prevention of diphtheria in different countries? What is the strategy of the treatment of this disease? Normal flora of the respiratory tract Oral cavity and pharynx - permanent flora - transient flora H. influenzae S. pyogenes Throat culture of a 5-year old child without symptoms Permanent flora: Transient flora: Streptococci (other than group A) H. influenzae (40-80%) Branhamella catarrhalis S. pneumoniae (20-40%) Neisseria spp. S. aureus Staphylococcus epidermidis N. meningitidis (5-20%) Bacteroides, Fusobacterium S. pyogenes (5-10%) Spirochetes Diphtheroides Lactobacillus Veillonella Peptostreptococcus, Peptococcus Actinomyces Yeasts Klebsiella spp., E. coli Haemophilus parainfluenzae Haemophilus spp. May be responsible for respiratory tract infections!!!! Beta-lactamase producing strains present in the upper respiratory tract as normal flora Staphylococcus aureus Haemophilus influenzae Haemophilus parainfluenzae Branhamella (Moraxella) catarrhalis Bacteroides fragilis Prevotella (Bacteroides) melaninogenica Fusobacterium nucleatum aerobes anaerobes Why is it important to know about these members of normal flora? Repeated GABHS pharyngitis versus carrier status (positive culture result for GABHS) - Treatment failure - GABHS carrier if - signs and symptoms of viral infection are present - wrong season - little clinical response to antibiotics (penicillin or amoxi/clav) - GABHS present between episodes - no ASO or AD-ase response - same serotype of GABHS - Repeated GABHS pharyngitis (infection) signs and symptoms consistent with GABHS (5-15 years) seasonal clustering (September to March) marked clinical response to specific antibiotics no GABHS between episodes ASO or AD-ase responses different serotypes of GABHS Normal flora of the respiratory tract Oral cavity and pharynx permanent flora transient flora External ear, nose - members of the normal skin flora Middle ear, sinuses, larynx, and lower respiratory tract - sterile Pathomechanism of upper and lower respiratory tract infections Simple virus infection Decreased ciliar activity, destroyed epithelial cells + Increased amount of mucus, swollen mucous membrane Nasopharyngeal flora Otitis media, sinusitis, bronchitis, CBAE, pneumonia Taking samples in the case of upper respiratory tract infections The best method is the nasopharyngeal swab Case 2 The patient was a 70-year-old female who was diagnosed with multiple myeloma 1 year before. She received immuno-suppressive drugs, with the last cycle completed 6 weeks before. The patient presented with a 2-day history of dyspnoea and a productive cough. She denied haemoptysis, night sweats, fever, chills, abdominal pain, nausea, vomiting and chest pain. Case 2 (cont.) Physical examination: 38.8oC, pulse 120/min, respiratory rate 20/min, bilateral crackles with expiratory wheezes. X-ray: bilateral, diffuse pulmonary infiltrates with effusion, pO2: 38 mmHg. Pleural exudate was seen. What kind of samples would you send to the microbiology laboratory? Case 2 (cont.) Samples for microbiology: - two sets of blood cultures!!!, - pleural puncture Empirical antibiotic treatment was started with cefotaxim + clindamycin iv. Case 2 ( cont.) • What is the organism causing this patient’s infection? Gram stained direct smear of the pleural fluid Streptococcus pneumoniae Blood culture became also S. pneumoniae positive Case 2 ( cont.) No sputum sample was taken for culture. Why not? Interpretative criteria for evaluating sputum samples After homogenization, the direct Gram-stained sputum will be checked microscopically (100x magnification) <10 epithelial cells / microscopic field >25 leucocytes / microscopic field The sample originates from the lower respiratory tract. Bacteria should be looked for around the leucocytes. MiniBal for taking lower respiratory tract specimens Case 2 (cont.) What risk factors does this woman possess for developing infection with this organism? What other populations are at risk of infection with this organism? Risk factors of this patient: age, malignacy, immunosupressive therapy Other patients in risk: asplenic patients (sickle cell dis.) age of >65 and <2 years diabetes chronic dis. (heart, liver, kidney) organ transplantation immunsupression (HIV, etc.) Case 2 (cont.) What do you think about the empiric antibiotic usage in this case? (cefotaxim and clindamycin) Case 2 (cont.) What do you know about the resistance problems of S. pneumoniae? How do you interpret the susceptibility test results in the present epidemiology situation in Hungary and in other parts of the world? Distribution of p-IM and p-R isolates of S. pneumoniae Hungary San Francisco, USA 31% 23% 33% 10% Pokfulam , Hong Kong 2% 71% New York, USA 19% 24% Mexico City, Mexico 30% 26% Riyadh, Saudi Arabia 50% 29% Sao Paulo, Brazil 15% 1% Johannesburg, South Africa 33% 11% pen-IM (penicillin MIC 0.12–1 µg/ml) pen-R (penicillin MIC 2µg/ml) The Alexander Project 1998, SmithKline Beecham Distribution of different serogroups of penicillinresistant S. pneumoniae strains in Europe 6B 6B 23F USA 6B 23F 6B 9V 9V 19A 23F South Africa Is MIC determination important during routine bacteriological testing? • Yes !! – Quantitative versus qualitative/semi quantitative – Helps to select the best antibiotic for the treatment of the index patient. – Many pharmaco-dynamic and pharmaco-kinetic parameters can not be calculated without it Case 3 A 10-year-old boy had long-standing allergic symptoms, including nasal discharge and congestion. He had symptoms of acute sinusitis several times in the past. For 3 days he had left-sided facial pain and headache with progressive swelling of the left eye. On physical examination, he was febrile to 38.4oC (101.2o F). When his lids were mechanically averted, his left globe was frozen and there was intense chemosis of the conjunctiva. Case 3 (cont.) An axial computer tomography (CT) scan showed anterior and lateral displacement of the left eye. There was an air-fluid level in the area between the lateral border or the left ethmoid and the median rectum of his left eye. The coronal CT showed air-fluid levels in his orbit, ethmoid sinus and maxillary sinus. An operation was decided using antibiotic ?prophylaxis? (imipenem + cilastatin). During the operation, pus was taken and sent to the laboratory in an anaerobic transport vial. Blood cultures were also taken during the febrile period. Culture results obtained after 48-h incubation in aerobic and anaerobic environment From the pus obtained from the sinus Aerobes: S. aureus H. influenzae Streptococcus alfa-haemolyticus Anaerobes: Veillonella parvula Fusobacterium necrophorum Porphyromonas gingivalis From the blood culture: S. aureus Colonies on the anaerobic blood agar plate after 48 hours of incubation Fusobacterium necrophorum Porphyromonas gingivalis Veillonella parvula Str. alfa-haemolyticus The blood culture was positive after 6 hours of incubation in a blood-culture automat. Gram-stain, catalase and coagulase positivity proved that the isolate is a S. aureus (oxacillin and clindamycin sensitive) Case 3 (cont.) What kind of antibiotic treatment should be used in this case? If the MD will decide to continue only the imipenem+cilastatin it will be a good decision? Case 4 A 16-year-old boy, otherwise healthy, became subfebrile in November with an inproductive cough and clinical signs of unilateral pneumonia. No empiric antibiotic therapy was introduced before a sputum sample was taken for culturing. Direct microscopic examination showed a few leucocytes. After 24-h incubation of the culture plates, besides the normal flora of the oropharynx, a few S. pneumoniae colonies were seen. In accordance with the susceptibility test results, 2x0.5 g/day cefuroxim was used for 3 days p.o. The patients state worsened, with increasing dyspnoe, and a not too sever diarrhoea started. The antibiotic treatment was changed: josamycin (a macrolide) was started 2x500 mg/day p.o. (due to the suspicion of another pathogen), but after a further 2 days no improvement in the pneumonia was observed, only the diarrhoea worsened. Case 4 (cont.) The therapy was changed again (i.v. ceftriaxon - third generation cephalosporine) the diarrhoea improved, but the pneumonia did not resolve. The next change in the antibiotic therapy was claritromycin (macrolide) 2x150 mg/day iv. This time the patient improved rapidly. The positive result of the investigation of the antibodies against Mycoplasma pneumoniae in the paired serum samples proved its aetiological role. Case 4 (cont.) What was the main problem with the clinical and laboratory diagnosis? Why did the first macrolide therapy not lead to an improvement? What are the advantages and disadvantages of oral antibiotic therapy? What can be done if disbacteriosis takes place? Pneumonia (1) • Community-acquired pneumonias (CAP) Neonatal period: Chlamydia trachomatis viruses (RS, adeno, parainfluenza) Streptococcus agalactiae Infants: viruses (influenza, parainfluenza, RS, adeno) Haemophilus influenzae b Streptococcus pneumoniae Children (>3 month to teenagers, young adults): Mycoplasma pneumoniae Chlamydia pneumoniae (Streptococcus pneumoniae, Legionella) Elderly: Streptococcus pneumoniae, Legionella spp Pneumonia (2) • Hospital-acquired pneumonias (HAP) Without predisposing factors, in less sever cases: Staphylococcus aureus Enterobacteriaceae In sever cases multi-resistant nosocomial strains Enterobacter cloaceae Klebsiella pneumoniae Pseudomonas aeruginosa Acinetobacter baumanii MRSA /MRSE Pneumonia (3) • Special cases: anaerobes S. pneumoniae H. influenzae Enterobacteriacae Splenectomy: S. pneumniae H. influenzae Cystic fibrosis: S. aureus Pseudomonas aeruginosa Burkholderia cepacia Diabetes, trauma of the head: S. aureus, MRSA /MRSE Corticosteroid therapy: Legionella spp Long stay in ICU: Pseudomonas aeruginosa Exposure to birds /animals: Q fever, psittacosis, viral pneumonia AIDS: P. carinii, atypical Mycobacterium, fungi etc. Aspiration pneumonia: CBAE and smoking: Prevention of nosocomial pneumonia • • • • • • • • Hand-washing and other routine infection-control practices Elevate the head of the bed Effective pain control and chest physiotherapy Agents that do not elevate gastric pH is preferred for stressulcer prophylaxis (sucralfate) Immunization Discourage smoking before surgery Ventilator tube should be changed regularly Rational antibiotic selection for empiric therapy and change to specific therapy as soon as possible (Dal Nogare A.L. 1994.) Case 5. • 48-year old female with high temperature, productive cough was taken to the emergency department of the hospital. • From her anamnesis it was known – Since two years Wegener granulomatosis was diagnosed – Three weeks before she had a mild diarrhoea which improved for diet. She has not visited her doctor. • Laboratory results: signs of infection, anaemia • However the laboratory results did not defer from those obtained one month before when she did not have any symptoms RTX: In the left lung infiltrate with desolation in the middle Opinion: it can be an abscess, but it can be caused by the underlying disease (vasculitis) Main question is to determine abscess or symptom of the underlying disease? Antibiotic?? Immunosuppressive therapy?? What kind of disadvantages are there for the patient if no correct decision is achieved? What kind of laboratory tests could be used to confirm diagnosis? Culture of the lower respiratory tract specimen (sputum) How can the laboratory confirm that the specimen is from the lower respiratory tract? The direct microscopy of the sputum sample 5. Case (cont.) • 3 „sputum” samples were received from the patient during the next days. • Results sent back to the clinician were „no lower respiratory tract specimen” • Consultation between the MD and the CM. • Next sample reached the requirements: • Culture result: Salmonella enteritidis >105 CFU/ml How did this Salmonella enteritidis got to the lung of the patient? Why is it important to treat mild enteric infection of a chronic patient? What should be used as an antibiotic in this case? Last question How would you select empiric antibiotic therapy in the case of pneumonia?