Presentation on theme: "Respiratory Tract Infections Prof. M.Awad Tag Eldin."— Presentation transcript:
Respiratory Tract Infections Prof. M.Awad Tag Eldin
Infections Of The Respiratory Tract Respiratory infections are mainly caused by bacteria, viruses, or Mycoplasma pneumonia. Rickettsial and fungal infections are relatively uncommon and are largely confined to certain geographical regions. Respiratory infections occur at any age but are commonest6 in the young, the elderly and the immunosuppressed. The clinical features are determined by the causal organism, the site of infection and whether the infection in acute or chronic.
Acute Respiratory Infections Acute infections predominantly involve the upper respiratory tract, e.g. coryza, the bronchial tree, e.g. acute bronchitis or the lungs, e.g. pneumonia, lung abscess.
Acute Exacerbation of Chronic Bronchitis A sustained worsening of respiratory symptoms that is acute in onset and usually requires a patient to seek medical help or alter treatment.
PNEUMONIA, DEFINITION A syndrome caused by acute infection characterized by clinical and/or radiographic signs of consolidation of a part or parts of one or both lungs.
LUNG ABSCESS AND EMPYEMA Definition A lung abscess is a localized area of pulmonary suppuration and necrosis with a central cavity, caused by infection with pyogenic organisms.
Bronchiectasis Definition Bronchiectasis is the term used to described pathological dilation of the bronchi. Secretions accumulate in the bronchiectasisbronchi and chronic infection causes persistent cough and purulent sputum.
Egyptian Picture of RTIs Prof. M.Awad Tag Eldin
Epidemiology of RTIs in Egypt
Acute Respiratory Tract Infections in developing countries among children 5 years of age A large proportion of ARI is present as pneumonia or bronchiolitis. Dr Thamer.K.Yousif/MBCh.B/FICMS, DR.BAN A. Khaleq/MSC. Middle East Journal of family medicine. 2006, 14;3.
Acute Respiratory Tract Infections in developing countries among children 5 years of age Incidence of ARI is almost the same all over the world : 5-7 episodes/ child/ years in urban areas 3-5 episodes in rural areas. Dr Thamer.K.Yousif/MBCh.B/FICMS, DR.BAN A. Khaleq/MSC. Middle East Journal of family medicine. 2006, 14;3.
Egyptian Data on Acute Febrile Illness due to different pathogens Acute respiratory infections are the second leading cause of death in Egyptian infants (1). For *55 months, 10,130 patients meeting the case definition of # AFI had a clinical evaluation, 1,005 (10%) patients had positive blood cultures including : 77 with Staphylococcus aureus 494 with ST infection 275 with Brucella 159 with other bacterial pathogens. *Between March 1999 and October 2003 # Acute Febrile Illness Am. J. Trop. Med. Hyg., 73(2), 2005, pp International Development Research Center, Egypt.
Epidemiology of *MRSA in Egypt *MRSA: Methicillin Resistant Staph. Aureus Indexed in MedLine as: Euro Surveill 2006;11(7):164-7
Epidemiology of Penicillin & Erythromycin-Resistant Strains Indexed in MedLine as: Euro Surveill 2006;11(7):164-7
Group A Streptococcal Pharyngitis in School-aged Children and Their Families for 16 months The incidence of group A streptococcal Pharyngitis is 13% for school-aged children (5-12 years). In families who had a primary case, 43% had at least 1 secondary case The incidence in adults is higher than expected. Pediatrics Nov ;120 (5):
Acute Respiratory Tract Infections in developing countries among children 5 years of age Conclusion: In all countries ARI is a leading cause of hospitalization and death. The WHO estimate that in 1990 ARI tragically caused 13 million children die each year, 4.3 million children die from ARI, mostly pneumonia, every year in developing countries. Antibiotics were the most common types of medications used by cases before presenting to hospital, which didn’t prevent children from reaching the hospital indicating misusage of antibiotics. Dr Thamer.K.Yousif/MBCh.B/FICMS, DR.BAN A. Khaleq/ MSC. Middle East Journal of family medicine. 2006, 14;3.
Lower Respiratory Tract Infections
Types of Bronchitis Acute bronchitis usually comes on quickly and gets better after 2 to 3 weeks. Approximately 90% of these infections are viral in origin. Most cases of acute bronchitis are viral or noninfectious. Secondary bacterial infection of acute bronchitis SBIAB by such bacterial pathogens as Streptococcus pneumoniae or Haemophilus influenzae may occur.
Types of Bronchitis Chronic bronchitis is defined as a condition characterized by cough and sputum production on most days during 3 consecutive months for >2 successive years. Chronic bronchitis has a very high incidence in smokers and it is also known as “ the smokers ’ disease ”. Acute exacerbation of chronic bronchitis (AECB) is characterized by increased cough, sputum production, and dyspnea, in addition to development of sputum purulence.
Etiology of Bronchitis Non-infectious bronchitis Due to prolonged exposure to chemicals, cigarette smoke and pollutants. Allergens (pollen, dust particles) are also triggers of non-infectious bronchitis. Infectious bronchitis Involves infection with microorganisms and its usually more intense. Common infectious agents are bacteria, viruses, mycoplasmas and fungal organisms.
Triggering factors for Acute Bronchitis Smoke. Certain dusts or fumes may develop occupational bronchitis. Gastro esophageal reflux disease (GERD). Low resistance, This may result from another acute illness, such as a cold, or from a chronic condition that compromises your immune system.
Triggering factors for Chronic Bronchitis Smoking. Air pollution and dust or toxic gases. Sometimes, chronic inflammation of the airways may lead to asthma. The bacteria identified during acute exacerbations of chronic bronchitis are often the same as those present in the airways of stable chronic bronchitis.
Diagnosis of Bronchitis Cold-like symptoms (runny nose, sneezing, and dry cough). Cough soon becomes deep and painful accompanied by wheezing with a greenish-yellow sputum. Fever of up to 39°C is common. Shortness of breath Chest radiography may be necessary to exclude pneumonia. A sputum culture may be performed, especially if green or bloody.
Treatment of Bronchitis Non-Pharmacological Treatment: Plenty of fluids, having rest, and avoiding smoking are useful. Pharmacological Treatment: Cough with sputum should not be treated because it helps remove mucus and other harmful materials from the lungs. Analgesics and antipyretics can also be useful. Acute bacterial bronchitis and Secondary bacterial infection of acute bronchitis can be treated with Antibiotics.
Meta-Analysis of the Benefits of Antibiotics in AECB –1.01.0– Elmes et al Berry et al Fear, Edwards Elmes et al Petersen et al Pines et al Nicotra et al Anthonisen et al Jorgensen et al Overall Favors PlaceboFavors Antibiotic Effect Size Saint S et al. JAMA. 1995;274:
Treatment of Bronchitis The ideal antibiotic for AECB must: Be active against the likely pathogens Be resistant to destruction by bacterial beta- lactamases Have high concentrations in lung parenchyma against target organisms Have a bacterial killing mechanism that does not increase airway inflammation.
Treatment of Bronchitis in Egyptian Outpatient Clinic Antibiotics were used in 50% of cases with bronchitis and wheezy bronchitis 3.5% of cases of the common cold. Amoxicillin was the most commonly used antibiotic in Pharyngitis, tonsillitis and wheezy bronchitis. The duration of antibiotic therapy was < 7 days in 82.6% of cases of tonsilitis and 60% of pneumonia. A. Zaki, M. Abdel-Fattah, A. Bassili, M. Arafa and R. Bedwani. Eastern Mediterranean Health Journal Volume 5, Issue 2, 1999, Page
2. Community Acquired Pneumonia
Community Acquired Pneumonia (CAP) CAP is a disease in which individuals who have not recently been hospitalized develop an infection of the lungs (pneumonia). CAP often causes problems like breathing, fever, chest pains, and cough. CAP occurs because the areas of the lung which absorb oxygen (alveoli) from the atmosphere become filled with fluid and cannot work effectively.
Resistance for Antibiotics
Epidemiology of CAP It is a major cause of death among all age groups. WHO estimates that 1 in 3 newborn infant deaths are due to pneumonia with over 2,000,000 worldwide deaths a year. More cases of CAP occur during winter months than during other times of the year.
Symptoms of CAP Breathing problems Cough with greenish or yellow sputum Fever that may be accompanied with sweating, chills, and uncontrollable shaking Chest pain Less common symptoms include: Bloody cough Headaches (including migraine) Loss of appetite & excessive fatigue Blueness of the skin (cyanosis) Nausea, vomiting & diarrhea joint pain (arthralgia) & muscle aches (myalgia)
Symptoms of CAP Older people might experience different manifestations of pneumonia : New or worsening confusion Hypothermia Falls Additional symptoms for infants could include: Being overly sleepy Yellowing of the skin (jaundice) Difficulties in feeding
Diagnosis of CAP Hypotension Tachycardia Changes in the amount of oxygen in the blood. Rales in breath Increased vibration of the chest when speaking. X-rays, and blood tests of blood and sputum are commonly used.
Distribution of Pathogens in CAP Bartlett JG, Mundy LM. N Engl J Med. 1995;333:1618; American Thoracic Society. Am J Respir Crit Care Med. 2001;163:1730’ Hall MJ, Owings, MF National Hospital Discharge Survey. NCHS. 2002:1; National Vital Statistics Report. 2001;49:14. Marrie TJ et al. Resp Med. 2005; 99: H parainfluenzae 1.9% H influenzae 4.9% M pneumoniae 15% M Catarrhalis 1.1% Unknown 51.6% S pneumoniae 5.9% C pneumoniae + M pneumoniae 2.1% S aureus 1.1% C pneumoniae 12%
Micro organisms causing CAP In Adults; Viruses cause 20% of CAP cases; Influenza, Parainfluenza, Respiratory syncytial virus, Metapneumovirus, Adenovirus.
Micro organisms causing CAP In Children > 5 years and teenagers; Are more likely to acquire Mycoplasma pneumonia and Chlamydophila pneumonia than adults & children < 5 years of age.
Treatment of CAP *ATS & **BCTS, established guidelines for the management of adults with CAP which divided individuals with CAP into four categories: 1.Healthy outpatients without risk factors 2.Outpatients with underlying illness and/or risk factors 3.Hospitalized individuals not at risk for Pseudomonas 4.Individuals requiring intensive care at risk for Pseudomonas
Complications of CAP Severe complications can result from CAP, including: Sepsis Respiratory failure Pleural effusion and empyema Abscess
1- Introduction to Antibiotics 1.1 Development of Antibiotics Synthetic era arrived around 1900 and involved The development of various dyes To treat bacterial infections as pyocyanas produced by Pseudomonas aeruginosa First era started from 1600 to 1900 and involved The use of Cinchona bark in the Treatment of malaria Miracle era which arrived when Alexander Fleming Discovered Penicillin in 1929 and apparently recognized by Flory and his team in 1940
There are four types of antimicrobial resistance Inherent (Natural) Resistance: Bacteria may be inherently resistant to an antibiotic by establishing a barrier against the antibiotic or lacking a transport system Acquired Resistance: Bacteria can develop resistance to antibiotics which results from changes in the bacterial genome either by mutation and selection or exchange of genes between strains and species Vertical evolution A spontaneous mutation in the bacterial chromosome which imparts resistance to a member of bacterial population Horizontal evolution : The acquisition of genes for resistance from another organism e.g. a streptomycete has a gene for resistance to streptomycin (its own antibiotic), but somehow that gene escape and gets into E-Coli or Shigella 1- Introduction to Antibiotics (Cont) 1.2 Antibiotic Resistance
The minimum inhibitory concentration (MIC) is defined as the minimum concentration required to inhibit 50% of a bacterial population. MIC however, doesn’t represent an absolute value and the true MIC is somewhere between the lowest test concentration that inhibits the organism growth and the next lower test concentration The following table gives an indication of MIC values of a selected range of antibiotics against four reference strains. 1- Introduction to Antibiotics (Cont) 1.3 Quantitative Susceptibility
AntibioticS. aureusE. faecalisE. coliP. aeruginosa Amikacin Azithromycin Cefaclor1-4> Cefazolin0.25-1> Cefuroxime Chloramephenicol Clarithromycin Erythromycin Gentamycin Ofloxacin Penicillin G Tetracycline Vancomycin Acceptable quality control ranges of MICs (ug/ml) for reference strains (NCCLS, 1991)
2- Classification of Antibiotics The most common methods classifies the antibiotics according to their chemical structure, as generally they will show similar patterns of activity, effectiveness, toxicity and allergic potential. 1- Penicillins 2- Cephalosporins 3- Tetracyclines 4- Quinolones 5- Sulphonamides 6- Aminoglycosides 7- Imidazoles 8- Glycopeptides 9- Macrolides 10- Linezolid
2- Classification of Antibiotics (Cont) 1- Penicillins Natural penicillin: penicillin G and penicillin V potassium Penicillinaze-resistant penicillins: cloxacillin, methicillin & oxacillin Aminopenicillins : amoxicillin, ampicillin & bacampicillin Extended-spectrum penicillin: pipracillin, carbenicillin & mezlocillin Mechanism: Inhibit bacterial cell wall synthesis Coverage: gm +/- ve, Streptococcus, Enterococcus & Staphylococcus species. Adverse effects: Urticaria, pruritis, nausea, vomiting, diarrhea and abdominal pain.
2- Classification of Antibiotics (Cont) 2- Cephalosporins 1 st, 2 nd, 3 rd and 4 th generations Mechanism: They act by inhibiting mucopeptide synthesis in the bacterial cell wall (similar to penicillins) which leads to the destruction of the bacteria Coverage : They are divided into groups according their antimicrobial activity (will be discussed later) Side Effects: Similar to penicillins
2- Classification of Antibiotics (Cont) 3- Tetracyclines Tetracycline, Minocycline, Doxycycline, Lymecycline Mechanism: Inhibit bacterial protein synthesis Coverage : gm –ve, +ve, protozoa, Mycoplasma, Rickettsia, Chlamydia, syphilis and Lyme disease Side effects: Strong affinity to Calcium, discoloration of permanent teeth, pseudomembranous colitis and gastric upsets.
2- Classification of Antibiotics (Cont) 4- Quinolones Norfloxacin, Ciprofloxacin, Ofloxacin, Enoxacin Mechanism: Inhibit bacterial DNA synthesis Coverage: First oral antibiotics effective against gm –ve bacteria and some gm +ve bacteria Therapeutic uses: Lower Respiratory Tract infections Bone and joint infections and urinary tract infections Side Effects: headache, fatigue, nausea, increased liver Function and integumentary rash
Respiratory Quinolone The Quinolone class of antimicrobial agents has generated considerable interest since its discovery >40 years ago. Substantial progress has been made in our understanding of the molecular mechanisms of the action of Quinolones against pathogenic bacteria, the induction of resistance to Quinolones in these organisms, and the potential of each Quinolone compound to induce toxicity in treated patients.
The prolific development of the Quinolones began in 1962, when Lesher et al. made the accidental discovery of Nalidixic Acid as a by- product of the synthesis of the Antimalarial Compound Chloroquine.
Date Quinolone 1960–1969 Nalidixic acid 1970–1975 Cinoxacin 1975–1985 Norfloxacin 1985–1990 Ciprofloxacin, Ofloxacin 1990–1995 Temafloxacin, Sparfloxacin 1995–2000 Grepafloxacin, Levofloxacin, Trovafloxacin 2000–2005 Moxifloxacin, possibly Gemifloxacin and Garenoxacin in 2003 or later
Proposed classification of Fluoroquinolones Urinary agents (1960–1985) Nalidixic acid Cinoxacin Enoxacin Norfloxacin activity against common Enterobacteriaceae, short serum half-lives, renal elimination main use in UTI
Gram-negative systemic agents (1985–1995) Ciprofloxacin Ofloxacin Levofloxacin wide activity against Gram-negatives,including P. aeruginosa, marginal activity against Gram- positives, longer serum half-lives widely used against tissue-based and urinary infections
Broad spectrum systemic agents (1990– 2000) Temafloxacin Clinafloxacin Trovafloxacin wide activity against Gram- negatives,including P. aeruginosa for some agents, and Gram-positives, for some agents long serum half-lives, some activity against anaerobes widely used against a broad range of tissue based infections
Respiratory agents (1995 onwards) Levofloxacin Sparfloxacin Grepafloxacin Moxifloxacin Gatifloxacin Gemifloxacin Garenoxacin wide activity against Enterobacteriaceae, active against Gram-positives, especially S. pneumoniae, active against atypical bacteria, variable activity against anaerobes, long serum half-life main use in respiratory tract infection
2- Classification of Antibiotics (Cont) 6- Aminoglycosides Gentamycin, Neomycin, Streptomycin, Tobramycin and Amikacin Mechanism: Irreversible binding of 50S ribosomal protein synthesis Coverage : Most Broad gm – ve as Pseudomonas spp, E. coli, Proteus spp, Klebsiella spp and some gm +ve Side effects: Ototoxicity and nephrotoxicity are the Most significant side effects
2- Classification of Antibiotics (Cont) 5- Sulphonamides Co-trimoxazole, Trimethoprim, sulfadiazine, sulfamethiazole, sulphamethoxazole and sulfisoxazole Mechanism: Blocks bacterial cell metabolism by inhibiting enzymes Coverage : Most gm + ve and some gm – ve because of resistance Therapeutic use: Are used only in very specific situations, including treatment of urinary tract infection, in meningococcal strains, & as prophylactic for rheumatic fever Side-effects : may include disruption of the gastrointestinal tract and hypersensitivity.
2- Classification of Antibiotics (Cont) 7- Imidazoles Metronidazole Mechanism: Inhibit bacterial DNA synthesis Coverage and effects: - Anaerobic gm-ve bacilli, including most Bacteroides species, Fusobacterium and Veillonella; anaerobic gm-ve cocci including Clostridium, Eubacterium, Peptococcus and Peptostreptococcus. -Metallic taste in mouth, nausea, upper abdominal pain or headaches sometimes occur after usual therapeutic doses
2- Classification of Antibiotics (Cont) 8- Glycopeptides Vancomycin, Bacitracin Mechanism: Inhibit bacterial cell wall synthesis Coverage and effects: - Broad gm + ve - Resistance is very rare - In most cases does not contribute to renal failure - Should be given every six hours as it is concentration Dependant - POOR LUNG PENETRATION
2- Classification of Antibiotics (Cont) 9- Macrolides Erythromycin, Azithromycin, Clarithormycin Mechanism: Inhibit bacterial protein synthesis. It reversibly bind 50S ribosome, and block peptide elongation Coverage : gm +/- ve, Streptococcus pyogenes, haemophilus Influenza, Syphilis, Lyme disease, Gonorrhea, Chlamydia And Mycoplasma Side effects: Nausea, vomiting, diarrhea and hepatoxicity
2- Classification of Antibiotics (Cont) 10- Linezolid Zyvox Mechanism: Inhibit bacterial protein synthesis Coverage : Bacteriostatic for VREF infections, S. aureus. Bactericidal for Strep pneumo, Strep pyogenes. Side effects Potential interaction with adrenergic and serotonergic agents
3- Cephalosporins Antibiotics Cephalosporins are semisynthetic derivatives from a fungus, they are structurally and pharmacologically related to Penicillins They are divided into four groups according to their antimicrobial activity 1 st Generation Cephalosporins: include molecules with the greatest activity against Gram positive bacteria 2 nd Generation Cephalosporins: Molecules with the greatest activity against Gram negative bacteria 3 rd Generation Cephalosporins: against Pseudomonas aeruginosa 4 th Generation Cephalosporins: against anaerobic bacteria
4- Efficacy of Antibiotics Evaluating antibacterial efficacy using pharmacokinetics and pharmacodynamics Pharmacokinetics (PK) - serum concentration profile - penetration to site of infection Pharmacodynamics (PD) susceptibility – MIC (potency) concentration- vs. time-dependent killing persistent (post-antibiotic) effects (PAE)
Conclusions: antibacterial choice for empiric use in RTI Most clinical studies do not show clinical differences between agents PK/PD parameters correlate with bacteriological and clinical outcome in animal models and in humans PK/PD parameters can be used to select agents with maximum potential for bacterial eradication Currently available agents vary significantly in achieving PK/PD parameters necessary for bacterial eradication
PNEUMONIA,CAP,TREATMENT A respiratory quinolone or a cephalosporin plus either a macrolide or a provides optimal coverage. Take into consideration: side-effect profiles, resistance potential, pharmacokinetics, and cost of individual agents.
ATS/evidence-based American Thoracic Society Outpatient treatment Cardiopulmonary disease ± modifying factors: ß-lactam (eg, cefuroxime, high-dose amoxicillin, amoxicillin/clavulanate) + (macrolide or doxycycline) or antipneumococcal fluoroquinolone. Hospital treatment With cardiopulmonary disease ± modifying factors: ß-lactam (eg, cefotaxime, ceftriaxone, ampicillin/sulbactam, high- dose ampicillin, IV) + (macrolide or doxycycline, IV or oral) or antipneumococcal fluoroquinolone (IV)
IDSA/evidence-based Infectious Diseases Society of America Outpatient treatment Macrolide, doxycycline, or antipneumococcal fluoroquinolone (alternative: ß-lactam (eg, amoxycillin/clavulanate, cefuroxime), but these agents not active against atypical pathogens) For older patients with comorbidities, the fluoroquinolone may be a preferred choice Hospital treatment Extended-spectrum cephalosporin + macrolide or ß-lactam/ß-lactamase inhibitor + macrolide or fluoroquinolone
Canadian Infectious Diseases Society/Canadian Thoracic Society/evidence-based Outpatient treatment Without modifying factors: macrolide or doxycycline With modifying factors and COPD (no recent antibiotics or oral steroids): macrolide (eg, azithromycin or clarithromycin). Hospital treatment Nursing home resident or suspected S pneumoniae, Legionella pneumophila, or C pneumoniae: respiratory fluoroquinolone or ß- lactam (eg, cephalosporin) + macrolide
Canadian Infectious Diseases Society/Canadian Thoracic Society/evidence-based Outpatient treatment Recent antibiotics or oral steroids, H influenzae or Gram-negative pathogen suspected: respiratory fluoroquinolone or ß-lactam (eg, amoxicillin/clavulanate or second generation cephalosporin) – macrolide cephalosporin + macrolide
Canadian Infectious Diseases Society/Canadian Thoracic Society/evidence-based Outpatient treatment Suspected macroaspiration pneumonia (anaerobes): ß-lactam (eg, amoxicillin/clavulanate) ± macrolide or respiratory fluoroquinolone + (clindamycin or metronidazole)
Canadian Infectious Diseases Society/Canadian Thoracic Society/evidence-based Outpatient treatment Suspected home resident with suspected S pneumoniae, enteric gram-negative or H influenzae: respiratory fluoroquinolone or ß- lactam (amoxicillin/clavulanate or second-generation cephalosporin) + macrolide.
Canadian Infectious Diseases Society/Canadian Thoracic Society/evidence-based Outpatient treatment Nursing home resident with suspected S pneumoniae, enteric Gram-negative or H influenzae: respiratory fluoroquinolone or ß- lactam (eg, amoxicillin/clavulanate or second-generation cephalosporin) + macrolide
British Thoracic Society/evidence-based Outpatient treatment Nonsevere disease: ß- lactam (eg, amoxicillin) or macrolide (for patients with ß-lactam intolerance) Hospital treatment Nonsevere disease with nonclinical factors for admission: ß-lactam (amoxicillin) or macrolideNonsevere disease: ß-lactam (amoxicillin, oral, or ampicillin or benzylpenicillin, IV) + macrolide (oral or IV) or antipneumococcal fluoroquinolone (levofloxacin, oral or IV)
Spanish Respiratory Society/Spanish Society of Chemotherapy/Questionably evidence-based Outpatient treatment Mild disease, typical clinical presentation: ß-lactam (high-dose amoxicillin) or new-generation fluoroquinolone or macrolide (controlled prescribing due to resistance) Mild disease, atypical clinical presentation: macrolide or new- generation fluoroquinolone Hospital treatment ß-lactam (eg, amoxicillin/clavulanate, ceftriaxone, cefotaxime, IV) ± (macrolide or quinolone [eg, ciprofloxacin, oral or IV]) or new-generation quinolone (oral or IV)
French Society of Infectious Diseases/Questionably evidence-based French Society of Infectious Diseases/Questionably evidence-based Outpatient treatment Ambulatory with mild disease, no comorbidity: ß-lactam (eg, high-dose amoxicillin) or antipneumococcal fluoroquinolone (in patients with ß-lactam intolerance). For patients < 40 yr old with an atypical clinical picture: macrolide Hospital treatment Well-defined CAP: high- dose ß-lactam (eg, amoxicillin/clavulanate or ceftriaxone, IV)Well- defined CAP: high-dose ß- lactam (amoxicillin/clavulanate or ceftriaxone, IV)
French Society of Infectious Diseases/Questionably evidence-based Outpatient treatment Ambulatory patients with comorbidity, not immediately at risk: Well-defined CAP: high- dose ß-lactam (eg, amoxicillin/clavulanate or ceftriaxone, IV) Suspected atypical pathogens: high-dose ß- lactam/ß-lactamase inhibitor + macrolide or ß-lactam (eg, amoxicillin) + ofloxacin or ß-lactam (eg, ceftriaxone, IV/IM) + macrolide or new fluoroquinolone Hospital treatment Ambulatory patients with comorbidity, not immediately at risk: Well-defined CAP: high- dose ß-lactam (amoxicillin/clavulanate or ceftriaxone, IV) Suspected atypical pathogens: high-dose ß- lactam/ß-lactamase inhibitor + macrolide or ß-lactam (eg, amoxicillin) + ofloxacin or ß-lactam (eg, ceftriaxone, IV/IM) + macrolide or new fluoroquinolone
German Respiratory Association/Paul Ehrlich Society for Chemotherapy/Questionably evidence- based Outpatient treatment Younger patients (< 65 yr) without comorbidity: ß-lactams (eg, aminopenicillins/ß-lactamase inhibitors, cephalosporins), macrolides, antipneumococcal fluoroquinolones (eg, levofloxacin); doxycyline only in special cases.
German Respiratory Association/Paul Ehrlich Society for Chemotherapy/Questionably evidence- based Outpatient treatment Elderly patients and/or patients with comorbidity: ß-lactams (eg, aminopenicillins/ß- lactamase inhibitors, cephalosporins [eg, cefuroxime, cefotaxime]) or antipneumococcal fluoroquinolone (levofloxacin) Hospital treatment Severe pneumonia in elderly patients with comorbidity: ß- lactams (eg, acylaminopenicillins/ß- lactamase inhibitors, cephalosporins [eg, cefotaxime, ceftriaxone]) + (macrolide or antipneumococcal fluoroquinolones [eg, levofloxacin]) or ß-lactam (carbapenem) + macrolide or fluoroquinolone (eg, ciprofloxacin) + clindamycin