2Respiratory Tract Infections Prof. M.Awad Tag Eldin
3Infections 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.
4Acute Respiratory Infections Acute infections predominantly involvethe upper respiratory tract, e.g. coryza,the bronchial tree, e.g. acute bronchitis orthe lungs, e.g. pneumonia, lung abscess.
5Acute 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.
6PNEUMONIA, DEFINITIONA syndrome caused by acute infection characterized by clinical and/or radiographic signs of consolidation of a part or parts of one or both lungs.
8PNEUMONIA, Clinical Settings Community-acquired pneumonia (CAP).Hospital-acquired pneumonia (HAP).Aspiration pneumonia.Pneumonia in ICH.Pneumonia in HIV.
9LUNG ABSCESS AND EMPYEMA DefinitionA lung abscess is a localized area of pulmonary suppuration and necrosis with a central cavity, caused by infection with pyogenic organisms.
10Bronchiectasis 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.
13Acute 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.
14Incidence of ARI is almost the same all over the world : Acute Respiratory Tract Infections in developing countries among children 5 years of ageIncidence of ARI is almost the same all over the world :5-7 episodes/ child/ years in urban areas3-5 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.
15Egyptian 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 aureus494 with ST infection275 with Brucella159 with other bacterial pathogens.Am. J. Trop. Med. Hyg., 73(2), 2005, pp1.International Development Research Center, Egypt.*Between March 1999 and October 2003#Acute Febrile Illness
16Epidemiology of *MRSA in Egypt *MRSA: Methicillin Resistant Staph. AureusIndexed in MedLine as: Euro Surveill 2006;11(7):164-7
17Epidemiology of Penicillin & Erythromycin-Resistant Strains Indexed in MedLine as: Euro Surveill 2006;11(7):164-7
18Group 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 caseThe incidence in adults is higher than expected.Pediatrics Nov ;120 (5):
19Acute 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.
22Types of BronchitisAcute 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.
23Types of BronchitisChronic 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.
24Etiology of Bronchitis Non-infectious bronchitisDue to prolonged exposure to chemicals, cigarette smoke and pollutants.Allergens (pollen, dust particles) are also triggers of non-infectious bronchitis.Infectious bronchitisInvolves infection with microorganisms and its usually more intense.Common infectious agents are bacteria, viruses, mycoplasmas and fungal organisms.
25Triggering 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.
26Triggering 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.
27Diagnosis 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 breathChest radiography may be necessary to exclude pneumonia.A sputum culture may be performed, especially if green or bloody.
28Treatment 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.
29Meta-Analysis of the Benefits of Antibiotics in AECB –1.01.0–0.51.50.5Elmes et al. 1957Berry et al. 1960Fear, Edwards. 1962Elmes et al. 1965Petersen et al. 1967Pines et al. 1972Nicotra et al. 1982Anthonisen et al. 1987Jorgensen et al. 1992OverallFavors PlaceboFavors AntibioticEffect SizeAntibiotic treatment of acute exacerbation of chronic bronchitis (AECB) leads to improved outcomes.A meta-analysis of published randomized trials was conducted to determine the effectiveness of antibiotics in treating AECB. The analysis included randomized, placebo-controlled trials that enrolled patients having an exacerbation of chronic bronchitis, those that used an antibiotic in the treatment group and a placebo in the control group, and those that provided sufficient data to calculate an effect size.The overall summary effect size of the 9 trials satisfying all inclusion criteria was 0.22 (95% CI, 0.10–0.34), indicating a slight benefit in the antibiotic-treated group.Analysis of 6 studies that included data on changes in peak expiratory flow rate revealed a summary effect size of 0.19 (95% Cl, 0.03–0.35) and a summary change in peak expiratory flow rate of L/min (95% Cl, 4.96–16.54 L/min) in favor of the antibiotic-treated group. Hospitalized patients appeared to benefit more than outpatients, perhaps because they exhibit more complicating factors (eg, older age, comorbid illness) at the beginning of therapy.These analyses demonstrate a statistically significant improvement due to antibiotic therapy in AECB, particularly if patients have at least 2 of the 3 cardinal symptoms: increased dyspnea, increased sputum volume, and increased sputum purulence.References:Saint S, Bent S, Vittinghoff E, Grady D. Antibiotics in chronic obstructive pulmonary disease exacerbations: a meta-analysis. JAMA. 1995;273:Saint S et al. JAMA. 1995;274:
30Treatment of Bronchitis The ideal antibiotic for AECB must:Be active against the likely pathogensBe resistant to destruction by bacterial beta-lactamasesHave high concentrations in lung parenchyma against target organismsHave a bacterial killing mechanism that does not increase airway inflammation.
31Treatment of Bronchitis in Egyptian Outpatient Clinic Antibiotics were used in50% of cases with bronchitis and wheezy bronchitis3.5% 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
33Community 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.
35Epidemiology 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.
36Symptoms of CAP Breathing problems Cough with greenish or yellow sputumFever that may be accompanied with sweating, chills, and uncontrollable shakingChest painLess common symptoms include:Bloody coughHeadaches (including migraine)Loss of appetite & excessive fatigueBlueness of the skin (cyanosis)Nausea, vomiting & diarrheajoint pain (arthralgia) & muscle aches (myalgia)
37Symptoms of CAPOlder people might experience different manifestations of pneumonia :New or worsening confusionHypothermiaFallsAdditional symptoms for infants could include:Being overly sleepyYellowing of the skin (jaundice)Difficulties in feeding
38Diagnosis of CAP Hypotension Tachycardia Changes in the amount of oxygen in the blood.Rales in breathIncreased vibration of the chest when speaking.X-rays, and blood tests of blood and sputum are commonly used.
39Distribution of Pathogens in CAP H parainfluenzae1.9%H influenzae4.9%M pneumoniae15%M Catarrhalis1.1%Unknown51.6%S pneumoniae5.9%C pneumoniae +2.1%S aureusC pneumoniae12%Community-acquired pneumonia (CAP) is a common and serious illness.Pneumonia is the seventh leading cause of death in the United States1 and the most common cause of death due to infectious disease.2 Up to 5.6 million cases of CAP occur annually, with as many as 1.1 million of these requiring hospitalization.2Marrie and colleagues conducted an etiological study of CAP in an ambulatory setting. Despite considerable effort, their etiological diagnosis of CAP treated on an ambulatory basis was made in only half the patients. The most commonly identified pathogens were M pneumoniae, C pneumoniae, S pneumoniae, andH influenzae.3Treatment strategies for CAP are complicated by the emergence of bacterial strains that have become resistant to current antibiotics. Resistance is being identified with increasing frequency among S pneumoniae, H influenzae, M catarrhalis, and a number of enteric gram-negative bacteria.2References:1. Arias E, Smith BL. Deaths: preliminary data for National Vital Statistics Reports. March ;51(5):1-45; Niederman MS, Mandell LA, Anzueto A, et al. Guidelines for the management of adults with community-acquired pneumonia. Diagnosis, assessment of severity, antimicrobial therapy, and prevention. Am J Respir Crit Care Med. 2001;163: ; 3. Marrie TJ, Poulin-Costello M, Beecroft MD, Herman-Gnjidic Z. Etiology of community-acquired pneumonia treated in an ambulatory care setting. Resp Med. 2005;99:60-65.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; 99:60-65.
40Micro organisms causing CAP In Adults;Viruses cause 20% of CAP cases;Influenza,Parainfluenza,Respiratory syncytial virus,Metapneumovirus,Adenovirus.
41Micro 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.
42Treatment of CAP*ATS & **BCTS, established guidelines for the management of adults with CAP which divided individuals with CAP into four categories:Healthy outpatients without risk factorsOutpatients with underlying illness and/or risk factorsHospitalized individuals not at risk for PseudomonasIndividuals requiring intensive care at risk for Pseudomonas
43Complications of CAPSevere complications can result from CAP, including:SepsisRespiratory failurePleural effusion and empyemaAbscess
451- Introduction to Antibiotics 1.1 Development of AntibioticsAntimicrobial chemotherapy was developed in three erasMiracle era which arrivedwhen Alexander FlemingDiscovered Penicillin in 1929and apparently recognized byFlory and his team in 1940
461- Introduction to Antibiotics (Cont) 1.2 Antibiotic ResistanceThere are four types of antimicrobial resistanceInherent (Natural) Resistance:Bacteria may be inherently resistant to an antibiotic by establishing a barrier against the antibiotic or lacking a transport systemAcquired 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 speciesVertical evolutionA spontaneous mutation in the bacterial chromosome which imparts resistance to a member of bacterial populationHorizontal 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 ShigellaInherent resistance: for example as gram-ve bacterium which has an outer membrane that establishes a permeability barrier against the antibiotic or an organism can lack a transport system for the antibiotic
471- Introduction to Antibiotics (Cont) 1.3 Quantitative SusceptibilityThe 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 concentrationThe following table gives an indication of MIC values of a selected range of antibiotics against four reference strains.Inherent resistance: for example as gram-ve bacterium which has an outer membrane that establishes a permeability barrier against the antibiotic or an organism can lack a transport system for the antibiotic
48Acceptable quality control ranges of MICs (ug/ml) for reference strains (NCCLS, 1991) AntibioticS. aureusE. faecalisE. coliP. aeruginosaAmikacin1-464-2560.5-40.5-8Azithromycin0.28-1-Cefaclor>32Cefazolin0.25-1>16Cefuroxime0.5-22-8Chloramephenicol4-16ClarithromycinErythromycinGentamycin0.12-10.25-4Ofloxacin1-8Penicillin GTetracycline8-32Vancomycin
492- 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- Penicillins2- Cephalosporins3- Tetracyclines4- Quinolones5- Sulphonamides6- Aminoglycosides7- Imidazoles8- Glycopeptides9- Macrolides10- Linezolid
502- Classification of Antibiotics (Cont) 1- PenicillinsNatural penicillin: penicillin G and penicillin V potassiumPenicillinaze-resistant penicillins: cloxacillin, methicillin & oxacillinAminopenicillins: amoxicillin, ampicillin & bacampicillinExtended-spectrum penicillin: pipracillin, carbenicillin & mezlocillinMechanism: Inhibit bacterial cell wall synthesisCoverage: gm +/- ve, Streptococcus, Enterococcus &Staphylococcus species.Adverse effects: Urticaria, pruritis, nausea, vomiting, diarrhea and abdominal pain.
512- Classification of Antibiotics (Cont) 2- Cephalosporins1st , 2nd , 3rd and 4th generationsMechanism: They act by inhibiting mucopeptide synthesis in the bacterial cell wall (similar to penicillins) which leads to the destruction of the bacteriaCoverage : They are divided into groups according their antimicrobial activity (will be discussed later)Side Effects: Similar to penicillins
522- Classification of Antibiotics (Cont) 3- TetracyclinesTetracycline, Minocycline, Doxycycline, LymecyclineMechanism: Inhibit bacterial protein synthesisCoverage : gm –ve, +ve, protozoa, Mycoplasma, Rickettsia, Chlamydia, syphilis and Lyme diseaseSide effects: Strong affinity to Calcium, discoloration of permanent teeth, pseudomembranous colitis and gastric upsets.
532- Classification of Antibiotics (Cont) 4- QuinolonesNorfloxacin, Ciprofloxacin, Ofloxacin, EnoxacinMechanism: Inhibit bacterial DNA synthesisCoverage: First oral antibiotics effective againstgm –ve bacteria and some gm +ve bacteriaTherapeutic uses: Lower Respiratory Tract infectionsBone and joint infections and urinary tract infectionsSide Effects: headache, fatigue, nausea, increased liverFunction and integumentary rash
54Respiratory 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.
55The 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.
56Date Quinolone 1960–1969 Nalidixic acid 1970–1975 Cinoxacin 1975–1985 Norfloxacin1985–1990 Ciprofloxacin, Ofloxacin1990–1995 Temafloxacin, Sparfloxacin1995–2000 Grepafloxacin, Levofloxacin, Trovafloxacin2000–2005 Moxifloxacin, possibly Gemifloxacin andGarenoxacin in 2003 or later
57Proposed classification of Fluoroquinolones Urinary agents (1960–1985)Nalidixic acidCinoxacinEnoxacinNorfloxacinactivity against commonEnterobacteriaceae, short serumhalf-lives, renal eliminationmain use in UTI
58Levofloxacin Gram-negative systemic agents (1985–1995) Ciprofloxacin wide activity against Gram-negatives,including P. aeruginosa, marginal activity against Gram-positives,longer serum half-liveswidely used against tissue-based and urinary infections
59Broad spectrum systemic agents (1990–2000) TemafloxacinClinafloxacinTrovafloxacinwide activity against Gram-negatives,including P. aeruginosa for some agents, and Gram-positives, for some agentslong serum half-lives,some activity against anaerobeswidely used against a broad range of tissue based infections
60Levofloxacin Respiratory agents (1995 onwards) Sparfloxacin GrepafloxacinMoxifloxacinGatifloxacinGemifloxacinGarenoxacinwide activity against Enterobacteriaceae,active against Gram-positives, especially S. pneumoniae,active against atypical bacteria, variable activity against anaerobes, long serum half-lifemain use in respiratory tract infection
612- Classification of Antibiotics (Cont) 6- AminoglycosidesGentamycin, Neomycin, Streptomycin, Tobramycinand AmikacinMechanism: Irreversible binding of 50S ribosomalprotein synthesisCoverage : Most Broad gm – ve as Pseudomonas spp,E. coli, Proteus spp, Klebsiella spp and some gm +veSide effects: Ototoxicity and nephrotoxicity are theMost significant side effects
622- Classification of Antibiotics (Cont) 5- SulphonamidesCo-trimoxazole, Trimethoprim, sulfadiazine, sulfamethiazole, sulphamethoxazole and sulfisoxazoleMechanism: Blocks bacterial cell metabolism byinhibiting enzymesCoverage : Most gm + ve and some gm – ve because of resistanceTherapeutic use: Are used only in very specific situations, including treatment of urinary tract infection, in meningococcal strains, & as prophylactic for rheumatic feverSide-effects : may include disruption of the gastrointestinal tractand hypersensitivity.
632- Classification of Antibiotics (Cont) 7- ImidazolesMetronidazoleMechanism: Inhibit bacterial DNA synthesisCoverage and effects:Anaerobic gm-ve bacilli, including most Bacteroidesspecies, Fusobacterium and Veillonella; anaerobic gm-vecocci including Clostridium, Eubacterium, Peptococcusand Peptostreptococcus.-Metallic taste in mouth, nausea, upper abdominal pain orheadaches sometimes occur after usual therapeutic doses
642- Classification of Antibiotics (Cont) 8- GlycopeptidesVancomycin, BacitracinMechanism: Inhibit bacterial cell wall synthesisCoverage and effects:Broad gm + veResistance is very rareIn most cases does not contribute to renal failureShould be given every six hours as it is concentrationDependant- POOR LUNG PENETRATION
652- Classification of Antibiotics (Cont) 9- MacrolidesErythromycin, Azithromycin, ClarithormycinMechanism: Inhibit bacterial protein synthesis.It reversibly bind 50S ribosome, and block peptideelongationCoverage : gm +/- ve, Streptococcus pyogenes, haemophilus Influenza, Syphilis, Lyme disease, Gonorrhea, Chlamydia And MycoplasmaSide effects: Nausea, vomiting, diarrhea and hepatoxicity
662- Classification of Antibiotics (Cont) 10- LinezolidZyvoxMechanism: Inhibit bacterial protein synthesisCoverage : Bacteriostatic for VREF infections, S. aureus. Bactericidal for Strep pneumo, Strep pyogenes.Side effects Potential interaction with adrenergic and serotonergic agents
673- Cephalosporins Antibiotics Cephalosporins are semisynthetic derivatives from a fungus, they are structurally and pharmacologically related to PenicillinsThey are divided into four groups according to their antimicrobial activity1st Generation Cephalosporins: include molecules with the greatest activity against Gram positive bacteria2nd Generation Cephalosporins: Molecules with the greatest activity against Gram negative bacteria3rd Generation Cephalosporins: against Pseudomonas aeruginosa4th Generation Cephalosporins: against anaerobic bacteria
684- Efficacy of Antibiotics Evaluating antibacterial efficacy using pharmacokinetics and pharmacodynamicsPharmacokinetics (PK)- serum concentration profile- penetration to site of infectionPharmacodynamics (PD)susceptibility – MIC (potency)concentration- vs. time-dependent killingpersistent (post-antibiotic) effects (PAE)
69Conclusions: antibacterial choice for empiric use in RTI Most clinical studies do not show clinical differences between agentsPK/PD parameters correlate with bacteriological and clinical outcome in animal models and in humansPK/PD parameters can be used to select agents with maximum potential for bacterial eradicationCurrently available agents vary significantly in achieving PK/PD parameters necessary for bacterial eradication
70PNEUMONIA,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.
71ATS/evidence-based American Thoracic Society Outpatient treatmentCardiopulmonary disease ± modifying factors: ß-lactam (eg, cefuroxime, high-dose amoxicillin, amoxicillin/clavulanate) + (macrolide or doxycycline) or antipneumococcal fluoroquinolone.Hospital treatmentWith 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)
72IDSA/evidence-based Infectious Diseases Society of America Outpatient treatmentMacrolide, 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 choiceHospital treatmentExtended-spectrum cephalosporin + macrolide or ß-lactam/ß-lactamase inhibitor + macrolide or fluoroquinolone
73Canadian Infectious Diseases Society/Canadian Thoracic Society/evidence-based Outpatient treatmentWithout modifying factors: macrolide or doxycyclineWith modifying factors and COPD (no recent antibiotics or oral steroids): macrolide (eg, azithromycin or clarithromycin).Hospital treatmentNursing home resident or suspected S pneumoniae, Legionella pneumophila, or C pneumoniae: respiratory fluoroquinolone or ß-lactam (eg, cephalosporin) + macrolide
74Canadian Infectious Diseases Society/Canadian Thoracic Society/evidence-based Outpatient treatmentRecent 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
76Canadian Infectious Diseases Society/Canadian Thoracic Society/evidence-based Outpatient treatmentSuspected home resident with suspected S pneumoniae, enteric gram-negative or H influenzae: respiratory fluoroquinolone or ß-lactam (amoxicillin/clavulanate or second-generation cephalosporin) + macrolide.
77Canadian Infectious Diseases Society/Canadian Thoracic Society/evidence-based Outpatient treatmentNursing 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
78British Thoracic Society/evidence-based Outpatient treatment Nonsevere disease: ß-lactam (eg, amoxicillin) or macrolide (for patients with ß-lactam intolerance)Hospital treatmentNonsevere 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)
79Spanish Respiratory Society/Spanish Society of Chemotherapy/Questionably evidence-based Hospital treatmentß-lactam (eg, amoxicillin/clavulanate, ceftriaxone, cefotaxime, IV) ± (macrolide or quinolone [eg, ciprofloxacin, oral or IV]) or new-generation quinolone (oral or IV)Outpatient treatmentMild 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
80 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: macrolideHospital treatmentWell-defined CAP: high-dose ß-lactam (eg, amoxicillin/clavulanate or ceftriaxone, IV)Well-defined CAP: high-dose ß-lactam (amoxicillin/clavulanate or ceftriaxone, IV)
81French Society of Infectious Diseases/Questionably evidence-based Hospital treatmentAmbulatory 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 fluoroquinoloneOutpatient treatmentAmbulatory 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
82German Respiratory Association/Paul Ehrlich Society for Chemotherapy/Questionably evidence-based Outpatient treatmentYounger patients (< 65 yr) without comorbidity: ß-lactams (eg, aminopenicillins/ß-lactamase inhibitors, cephalosporins), macrolides, antipneumococcal fluoroquinolones (eg, levofloxacin); doxycyline only in special cases.
83German Respiratory Association/Paul Ehrlich Society for Chemotherapy/Questionably evidence-based Outpatient treatmentElderly patients and/or patients with comorbidity: ß-lactams (eg, aminopenicillins/ß-lactamase inhibitors, cephalosporins [eg, cefuroxime, cefotaxime]) or antipneumococcal fluoroquinolone (levofloxacin)Hospital treatmentSevere 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