Pulmonary hemorrhage. Pulmonary embolism. Pulmonary oedema. Pneumonia admissions and deaths (n=1339) 400 Survived Died 350 300 s t n e i t a p 250 f 200 o r e b m u N 150 Fig. 8.1.2 Bronchoalveolar cell carcinoma presenting as extensive consolidation on CXR. 100 50 Clinical features In the elderly, mental confusion and the lack of fever at presentation ar e more common than in younger patients. Pleuritic chest pain is more common in younger pati ents and has been associated with a good prognosis. Unusually, patients with Mycoplasma pne umoniae infection may display extra-pulmonary features, e.g. erythema multi- forma or other skin rashes in 25%, neurological signs in around 5%. No combination of clinical features a llows a con \201 dent pre- diction of the microbiological etiology. Infection with Mycopla sma pneumoniae, Legionella spp., Chlamydophila psit- taci or Coxiella burnetii generally in volves younger patients. 0 16 \200\22324 25 \200\22334 35 \200\22344 45 \200\22354 55 \200\22364 65 \200\22374 75 \200 \22384 85 \200\22394 >=95 Age range Fig. 8.1.1 Pneumonia admissions to 5 hospitals in a 1 year period. Microbiology Patients seen in the community (UK): \200 Streptococcus pneumoniae (36%). \200 Viruses (13%, mostly in \202 uenza A). \200 Haemophilus in \202 uenzae (10.2%). \200 Mycoplamsa pneumoniae (1.3%). Patients seen in hospital (UK): \200 \200 \200 \200 \200 \200 \200 Streptococcus pneumoniae (39%). Chlamydophila pneumoniae (13%). Viruses (12%, mostly in \202 uenza A). Mycoplamsa pneumoniae (11%). Haemophilus in \202 uenzae (5%). Legionella pn emophilia (3.6%). Chlamydophila psittaci (2.6%). Diagnosis A CXR is required to make a con \201 dent diagnosis of CAP. In one UK community study of adults with symptoms of a lower respiratory tract infection and focal chest signs, only 39% had CXR evidence of pneumonia. Differential diagnosis \200 Organizing pneumonia. \200 Bronchoalveolar cell carcinoma. \200 Eosinophilic pneumonia. \200 Vasculitis, e.g. Wegener \200\231s granulomatosis. \200 Allergic bronchopulmonary aspergillosis. Fig. 8.1.3 Organizing pneumonia presenting as consolidation. CHAPTER 8.1 Community-acquired pneumonia 167 Cavities, pneumatoceles, pneumothoraces in Staph aureus infection. Right upper lobe involve ment with a bulging interlobar \201 ssure in Klebsiella pneumoniae infection. Mediastinal lymphadenopathy in Mycoplasma pneumo- niae infection. AUTHOR \200\231S TIP \200 \200 \200 \200 \200 \200 Hotel stay in last 14 days \200\223 Legionella sp infection? Lambing or calving season \200\223 Q fever? Pet bird at home \200\223 Chlamydophila psittaci? Flu-like illness initi ally \200\223 Staphylococcus aureus? Travel to East Asia, very ill - Burkholderia pseudoma llei? Necrotising pneumonia, very ill \200\223 Staphylococcus aureus? Underlying structura l lung disease \200\223 Pseudomonas aeruginosa? Cluster of cases \200\223 outbreak? CT scanning is more sensitive than CXR for detecting the presence of consolidation. However , the clinical signi \201 - cance of CT abnormalities consistent with pneumonia in patient s with a normal CXR is unclear. Complete resolution of the CXR changes of pneumonia occurre d in 73% of cases at 6 weeks in one study. Resolution is generally slower in older patients , those with multilobar involvement and in legionella pneumonia. Investigations CRP A raised level of CRP is a more sensitive marker of pneu- monia than a r aised white cell count. In one study, all patients with CAP had a CRP of >50mg/l. Failure o f the CRP to fall by 50% within 4 days suggests treatment failure or the development of com plications. Further reading BTS Guidelines for the Management of Community Acquired Pneumonia in Adults. Thorax 2001; 56 Suppl 4: IV1 \200\22364. Campbell SG, Marrie TJ, Anstey R, et al.The contribution of blood cultures to the clinical management of adult patients admitted to the hospital with community-acquired pneumonia: a prospective observational study. Chest 2003; 123(4): 1142 \200\22350. Microbiological tests A full range of microbiological tests should be performed on patients admitted to hospital with severe CAP. This includes: \200 \200 \200 \200 \200 Jokinen C, Heiskanen L, Juvonen H, et al. Incidence of community- acquired pneumonia in the population of four municipalities in eastern Finland. Am J Epid 1993; 137(9): 977 \200\223 988. Lim WS, Macfarlane JT, Boswell TC, et al. Study of community acquired pneumonia etiology (S CAPA) in adults admitted to hospital: implications for management guidelines. Thorax 2001; 56(4): 296 \200\223301. Blood for culture and sensitivity. Sputum for culture and sensitivity. Urine for pneumococc al antigen. Urine for legionella antigen. Blood for serological tests for Mycoplasma pneumo niae, Chlamydophila spp. Legionella spp. Coxiella burnetti. Loeb M. Pneumonia in the elderly. Curr Opin Infect Dis 2004; 17(2): 127 \200\22330. Marston BJ, Plouffe JF, File TM, Jr., et al. Incidence of community- acquired pneumonia req uiring hospitalization. Results of a popu- lation-based active sur veillance Study in Ohio. The Community-Based Pneumonia Incidence Study Group. Archives of Internal Medicine 1997; 1 57(15): 1709 \200\2231718. Preferably, all samples for culture and sensitivity should be collected prior to administra tion of antibiotics. In patients with non-severe CAP, the yield from routine microbiologica l tests including blood and sputum cultures has been found to be low (<15%). Evidence of an improve- ment in clinical outcome consequent on microbiological testing in patients with n on-severe CAP and no co-morbid illness is lacking. Therefore, microbiological testing in no n- severe CAP should be guided by patient and health resource characteristics. Mittl RL, Jr., Schwab RJ, Duchin JS, et al. Radiographic resolution of community-acquired p neumonia. Am J Respir Crit Care Med 1994; 149(3 Pt 1): 630 \200\2235. Morgan M. Staphylococcus aureus, Panton-Valentine leukocidin, and necrotising pneumonia. Bmj 2005; 331(7520): 793 \200\2234. Smith RP, Lipworth BJ. C-reactive protein in simple community- acquired pneumonia. Chest 1995; 107(4): 1028 \200\2231031. Woodhead MA, Macfarlane JT, McCracken JS, et al. Prospective study of the etiology and outc ome of pneumonia in the com- munity. Lancet 1987; 1(8534): 671 \200\223674. AUTHOR \200\231S TIP Legionella and pneumococcal urinary antigen tests may remain positive for many weeks following infection. Radiological tests There are no features on CXR that allow a con \201 dent prediction of t he microbiological etiology. Nevertheless, certain patterns have been described: \200 Multilobar involvement in bacteraemic pneumococcal infection (more commonly than in non-bac teraemic pneumococcal infection). W-S LIM 168 8.1 \200\223 continued Community acquired pneumonia: severity assessment and antibiotic ma nagement Severity assessment An accurate assessment of disease severity is fundamental to the manage ment of CAP. The 2 most widely studied and used severity assessment tools in CAP are the Pn eumonia Severity Index (PSI) and the CURB65 score. Both these tools stratify patients accor ding to risk of mortality. The PSI requires the calculation of an index (range 70 \200\2233 00) from 20 parameters derived from patient demo- graphics, clinical \201 ndings and inve stigations. The practical simplicity of the CURB65 score is its main advantage over the PSI . CURB65 score \200\223 score 1 point for each parameter present: \200 \200 \200 \200 16.0% 14.0% 12.0% Penicillin resistance Tetracycline resistance Erythromycin resistance s e t a r 10.0% e c n a t s i s e R 8.0% 6.0% 4.0% 2.0% 0.0% 1999 2001 2003 Year 1997 2005 Confusion (mini-mental score <8 out of 10). Urea > 7mmol/l. Respiratory rate \211 30/min. Blood pressure: systolic <90mmHg or diastolic \211 60mmHg. Age \211 65 years. Fig. 8.1.4 Pneumococcal resistance rates to penicillin, erythromycin and tetracycline in En gland \200\223 data derived from invasive pneumococcal isolates from >44,000 patient episo des reported to the HPA Center for Infections (1997 to 2006). Infection by S. pneumoniae exhibiting low to moderate levels of penicillin resistance (MIC <4mg/L) does not alter CAP outcomes provided appropriate antibiotics (ie. beta-lactams) at adequate doses are used. Resistance rates of S. pneumoniae to the tetracyclines and \202 uoroquinolones remain low in the UK. Beta-lactamase production in Haemophilus in \202 uenz ae ranges from 2 \200\22317% in the UK. CURB65 score 0 1 2 3 to 5 Risk of death (%) 0.7 2.1 9.2 15 to 40 CURB65 score 0 \200\2231: patient may be suitable for home treatment. CURB65 score 2: patie nt may require short hospital stay. CURB65 score of 3 or more: patient should be managed in hospital as having severe CAP. Clinical judgment must always be exercised in all cases. CAP treated in the community \200 Antibiotic cover for atypical pathogens (Mycoplasma pneumoniae, Legionella spp. and Chlamyd ophila spp.) has not been found to confer any clinically signi \201 cant bene- \201 ts e xcept in cases of proven legionella pneumonia. For the majority of patients, beta-lactam ba sed mono- therapy is usually adequate (eg. amoxicillin 500 mg TDS PO). AUTHOR \200\231S TIP The 3 main reasons for admission to hospital other than disease severi ty are: \200 \200 \200 Non-severe CAP treated in hospital \200 \200 Antibiotic cover for atypical pathogens is indicated. This may involve beta-lactam and macr olide combina- tions or monotherapy with a new generation \202 uoroqui- nolone. social needs; worsening of other co-existing illness; eg. heart failure; patient \200\231s preference. Severe CAP treated in hospital \200 Adequate empirical antibiotic cover against S. pneumo- niae and Legionella spp. should be e nsured in all patients. Some data indicate that in bacteraemic pneumococcal pneumonia, comb ination therapy (beta-lactam + macrolide) is associated with lower mortality than beta-lact am monotherapy. Empirical combination IV antibiotics are therefore usu- ally indicated (e.g . beta-lactamase stable beta lactam + macrolide, or beta-lactam + \202 uoroquinolone). In selected patients, empirical therapy may need to be modi \201 ed to embrace other pathoge ns such as MRSA, Pseudomonas aeruginosa, Burkhoderia psuedomallei etc. Once clinical stabil ity is evident, antibiotics can be switched from IV to oral therapy. Antibiotic management \200 \200 Initial treatment of CAP is usually empirical. Empirical therapy is primarily directed at S treptococcus pneumoniae. Newer generation fluoroquinolones with enhanced Gram-positive acti on are active against both S. pneumo- niae and the atypical pathogens. Fluoroquinolones hav e a high bioavailability when taken orally. Administration of the \201 rst dose of antibi otic should occur as early as possible in view of some evidence that this confers in a surv ival bene \201 t in the context of CAP. Antibiotic resistance \200 Antibiotic resistance of S. pneumoniae is a world-wide concern. Rates are relatively low in the UK. CHAPTER 8.1 Community-acquired pneumonia 169 Further reading Annane D, Bellissant E, Bollaert PE, et al. Corticosteroids for severe seps is and septic shock: a systematic review and meta-analysis. Bmj 2004; 329(7464): 480. Duration of antibiotic The optimal duration of antibiotic therapy in CAP has not been estab lished. In general, the following apply: \200 \200 \200 Non-severe CAP: 5 \200\2237 days. Severe CAP: 10 days. Legionella, staphylococcal or Gram-n egative enteric bacilli pneumonia: 14 \200\22321 days. Antonelli M, Conti G, Moro ML, et al. Predictors of failure of nonin- vasive positive press ure ventilation in patients with acute hypox- emic respiratory failure: a multi-center stud y. Intensive Care Med 2001; 27(11): 1718 \200\2231728. Confalonieri M, Potena A, Carbone G, et al. Acute respiratory fail- ure in patients with se vere community-acquired pneumonia. A prospective randomized evaluation of noninvasive venti lation. American Journal of Respiratory & Critical Care Medicine 1999; 160 (5 Pt 1): 1585 \200\2231591. Other treatments Steroids \200 Moderate doses of steroid (hydrocortisone 300mg per day), given to patients with septic sho ck who do not mount an appropriate cortisol response to stimulation, have been shown in som e studies to improve clinical outcome. Patients with CAP comprised a large propor- tion of patients studied. There is continued debate regarding patient selection and steroid dose. Fine MJ, Auble TE, Yealy DM, et al. A prediction rule to identify low- risk patients with c ommunity- acquired pneumonia [see com- ments]. New England Journal of Medicine 1997; 336(4) : 243 \200\223250. Lim WS, van der Eerden MM, Laing R, et al. De \201 ning community acqui red pneumonia severity on presentation to hospital: an international derivation and validat ion study. Thorax 2003; 58(5): 377 \200\223382. Marrie TJ, Wu L. Factors in \202 uencing in-hospital mortality in com- munity-acquired pne umonia: a prospective study of patients not initially admitted to the ICU. Chest 2005; 127( 4): 1260 \200\2231270. Non-invasive ventilation (NIV) \200 A randomized controlled trial demonstrated that the use of NIV in patients with severe CAP who did not require immediate intubation but who were hypoxaemic or in respiratory distress led to a 25% reduction in the need for intubation. The bene \201 t was largely con \201 ned to the subgroup of patients with underlying COPD. The use of NIV has been shown to lead to a delay in intubation of some patients with CAP. Patients who require intubation follow ing a long period of \200\230failed NIV \200\231 have poorer outcomes. Meehan TP, Fine MJ, Krumholz HM, et al. Quality of care, process, and outcomes in elderly p atients with pneumonia [see com- ments]. JAMA 1997; 278(23): 2080 \200\2232084. Mills GD, Oehley MR, Arrol B. Effectiveness of beta lactam antibiot- ics compared with anti biotics active against atypical pathogens in non-severe community acquired pneumonia: meta- analysis. Bmj 2005; 330(7489): 456. Roson B, Carratala J, Dorca J, et al. Etiology, reasons for hospitaliza- tion, risk classes , and outcomes of community-acquired pneumo- nia in patients hospitalized on the basis of c onventional admission criteria. Clin Infect Dis 2001; 33(2): 158 \200\223165. AUTHOR \200\231S TIPS \200 Yu VL, Chiou CC, Feldman C, et al. An international prospective study of pneumococcal bacte remia: correlation with in vitro resistance, antibiotics administered, and clinical outcome . Clin Infect Dis 2003; 37(2): 230 \200\223237. A trial of NIV should only be considered in severe CAP where there is a clear plan in place regarding what to do in the event of failure. There is no good evidence that patients with out COPD bene \201 t from NIV in the context of severe CAP. Clinical response to a trial o f NIV should be assessed within 1 hour of NIV. If an inadequate response is observed, intub ation should not be further delayed. W-S LIM 170 8.1 \200\223 continued Community acquired pneumonia: other management issues Time to clinical stability Two-thirds of patients attain the following criteria for clinica l stability within 3 days of hospital admission: \200 \200 \200 \200 \200 \200 \200 temperature \211 37.8 C; heart rate \211 100/min; respiratory rate \211 24/min; systoli c BP \211 90mmHg; oxygen saturation \211 90%; ability to maintain oral intake; normal me ntal status. The median time to stability for heart rate and systolic BP is 2 days. For respiratory rate , oxygen saturation and temperature it is 3 days. Non-resolving CAP A lack of an adequate response to empirical therapy has been reported to occur in up to 15% of patients admitted with CAP. This is mostly evident within the \201 rst 72 hours. These patients have a longer length of hospital stay and increased mortality compared to patients who respond adequately. The risk of treatment failure is associated wi th the presence on the admission CXR of: \200 \200 \200 Fig. 8.1.5 Loculated parapneumonic effusion resulting in delay in resolution despite antibi otics. Discharge from hospital Based on the criteria for clinical stability (stated in Time to cli nical stability), a prospective cohort study of 680 patients reported that in patients ful \201 lling all the criteria on the day of discharge, death or readmission subsequently occ urred in 10.5% of patients compared to 46.2% of patients in whom \211 2 criteria were not met. No real bene \201 t has been found in delaying discharge by 24 hours following a swit ch from IV to oral antibiotics once clinical stability has been attained. pleural effusions; multilobar involvement; cavitation. Parapneumonic effusions occur in up to 57% of hospitalized patients with CAP. It is an impo rtant cause of a delay in resolution despite antibiotics. Nosocomial infections account for a \201 fth of \200\230non-resolving CAP \200\231 and has been found to be independently associated with increased mortality. Follow up Follow up at 6 weeks following hospital discharge is routinely practiced to: \200 \200 Causes of non-resolving CAP: \200\230CHAOS \200\231 \200 Complication \200\223 empyema; lung abscess; endocarditis; nosocomial infection particular ly Clostridium difficile infection. Host \200\223 immunocompromised host. Antibiotic \200 \223 inadequate dose; poor oral absorption; drug hypersensitivity. Organism \200\223 resis tant organism (eg. high level ( \211 4mg/L) penicillin resistant Streptococcus pneumoniae); unex- pected organism not covered by empirical antibiotics. Second diagnosis \200\223 pul monary embolism; underlying cancer; organizing pneumonia. ensure full or on-going resolution; detect previously undiagnosed conditions predisposing t o pneumonia, in particular lung cancer. This practice is currently not evidence-based. \200 CXR at follow up \200 In one study of CAP treated in the community, underly- ing lung cancer was detected on foll ow up CXR in 4% of 236 patients. In hospitalized patients, underlying lung cancer is usuall y identi \201 ed during the admission episode. Lung cancer was detected in less than 1% of patients on follow up CXR in a study of 1011 hospitalized patients. Procedures to consider in cases of delayed resolution include \200 \200 \200 \200 extended microbiological tests; CT scanning; pleural \202 uid sampling; bronchoscopy. Prevention Smoking is associated with an increased risk of CAP, pneu- mococcal bacteraemia and legionella infection. Smoking cessation advice should be offered to all current smokers . In \202 uenza vaccination of persons aged 65 years and above is effective in preventing respiratory illness, admission to hos- pital and death. Pneumococcal polysaccharide vaccina tion is effective at preventing invasive pneumoncoccal disease in persons aged 65 years and above (ef \201 cacy 44 \200\22375%, decreasing with age). In one series of patients with \200\230non-responding CAP \200\231, a sys- tematic approac h including invasive techniques enabled a speci \201 c diagnosis to be made in 73%, of whi ch over half were infectious causes. AUTHOR \200\231S TIP In the elderly and those with chronic lung disease, improvement may be slower than expected. CHAPTER 8.1 Community-acquired pneumonia 171 Pneumococcal polysaccharide vaccination can be safely given at the same time as in \202 ue nza vaccination. Re-immunization within 3 years is contraindicated due to the risk of sever e reactions. A second dose 5 years or more later has been shown to be safe, with only sligh tly more local reaction compared to the \201 rst dose. The safety or value of a third dos e has not been demonstrated. Currently, conjugate pneumococcal vaccines are availa- ble for children but not for adults. Halm EA, Fine MJ, Marrie TJ, et al. Time to clinical stability in patients hospitalized wit h community-acquired pneumonia: implications for practice guidelines. JAMA 1998; 279(18): 1 452 \200\2231457. Jackson LA, Neuzil KM, Yu O, Benson P, et al. Effectiveness of pneu- mococcal polysaccharid e vaccine in older adults. N Engl J Med 2003; 348(18): 1747 \200\2231755. Menendez R, Torres A, Zalacain R, et al. Risk factors of treatment failure in community acq uired pneumonia: implications for disease outcome. Thorax 2004; 59(11): 960 \200\223965. Nuorti JP, Butler JC, Farley MM, et al. Cigarette smoking and inva- sive pneumococcal disea se. Active Bacterial Core Surveillance Team [see comments]. 2000; 342(10): 681 \200\223689. Ramirez JA, Srinath L, Ahkee S, et al. Early-switch from intravenous to oral cephalosporins in the treatment of hospitalized patients with community-acquired pneumonia [see comments] . Arch of Intern Med 1995; 155(12): 1273 \200\2231276. Further reading Arancibia F, Ewig S, Martinez JA, et al. Antimicrobial treatment fail- ures in patients with community-acquired pneumonia: causes and prognostic implications. Am J Re spir Crit Care Med 2000; 162(1): 154 \200\223160. Ramirez JA, Bordon J. Early switch from intravenous to oral antibi- otics in hospitalized p atients with bacteremic community- acquired Streptococcus pneumoniae pneumonia. Arch Intern Med 2001; 161(6): 848 \200\223850. Gibson SP, Weir DC, Burge PS. A prospective audit of the value of \201 bre optic bronchos copy in adults admitted with community acquired pneumonia. Respir Med 1993; 87(2): 105 \200 \223109. Woodhead MA, Macfarlane JT, McCracken JS, et al. Prospective study of the etiology and outc ome of pneumonia in the com- munity. Lancet 1987; 1(8534): 671 \200\223674. Halm EA, Fine MJ, Kapoor WN, et al. Instability on hospital discharge and the risk of adver se outcomes in patients with pneumonia. Arch Intern Med 2002; 162(11): 1278 \200\2231284. W-S LIM 172 8.2 Hospital-acquired pneumonia: epidemiology and diagnosis De \201 nition Hospital-acquired pneumonia (HAP) is broadly de \201 ned as pneumonia occu rring 48 hours after hospital admission in the absence of any relevant symptoms or signs of infection at the time of admission. HAP includes the 3 following subgroups: \200 Ventila tor-associated pneumonia (VAP) \200 Health-care-associated pneumonia (HCAP) \200 Hospit al-acquired pneumonia in non-intubated patients. In the ICU setting, HAP accounts for 25% of all infections. VAP \200 VAP occurs in 9 \200\22327% of all intubated patients. The wide range in incidence rates re \202 ects differences in the de \201 ni- tion of pneumonia used to identify VAP. Half of all cases of VAP occur within 4 days of intubation. Patients with VAP have a mortality rat e of 20 \200\22355%. VAP increases LOS by a mean of 6 days. \200 \200 Diagnosis Diagnostic criteria for HAP The diagnosis of HAP is dif \201 cult. There are no diagnostic criteria for HAP that have both high (>90%) sensitivity and speci \201 city. Th e following criteria are offered by the 2008 British Society of Antimicrobial Chemotherapy HAP Guidelines to identify patients in whom HAP should be considered: \200 VAP \200 This is defined as pneumonia occurring more than 48 hours after endotracheal intubation. Th e vast majority of data on HAP is derived from studies of VAP. HCAP \200 The recognition of the speci \201 c subgroup of HCAP is relatively new. HCAP refers to pne umonia occurring in any of the following groups of patients: (a) Was hospitalized in an acu te care hospital for 2 or New or persistent radiographic infiltrate which is unexplained. Fever (>38 C). Leucocytosi s (>12 x 103/mm3)/leucopenia (<4 x 103/mm3). Purulent respiratory secretions. Increased oxy gen requirements. \200 \200 \200 more days within 90 days of infections. (b) Resided in a nursing home or long-term care facility. (c) Received recent IV antibiotic therapy, chemotherapy, or wound care within the past 30 days of the current infection. Speci \201 city for the diagnosis of HAP may be enhanced if microbiological criteria in ad dition to clinical criteria are required to establish the diagnosis. Acquiring the relevant microbiological data necessitates microbiological testing (often invasive) from the time o f clinical suspicion of HAP. This may lead to a delay in con \201 rming the diagnosis and to institution of antibiotics. The 2005 ATS/IDSA guidelines recommend that when HAP is susp ected on clinical criteria, empirical antibiotics are commenced unless there is both (a) a low clinical sus- picion for pneumonia and (b) negative microscopy of a lower respiratory t ract sample. The diagnosis of HAP should be reviewed within 72 hours in the light of micro- biological test results and the clinical response to empirical treatment. (d) Regularly attends a hospital or haemodialysis clinic. The main bulk of evidence that nu rsing home-acquired pneumonia (NHAP) should be managed differently from CAP arises from the United States. The only study of NHAP in the UK did not demonstrate any clinically relevan t differences from CAP in the microbiological aetiologies implicated. Data speci \201 c to HCAP are relatively limited. HAP in non-intubated patients \200 Although this subgroup of patients is the largest, there are relatively few studies speci \201 c to this area. In the only prospective study using advanced methods to determine micr obiological etiology in these patients, the frequency of pathogens identi \201 ed shared s imilarities with both CAP and VAP studies \200\223 Streptococcus pneumoniae was the most c ommon pathogen identi \201 ed (10% of cohort) following by Legionella spp. (4%), Enterobac teria (4%), Pseudomona aeruginosa (4%), and Acinetobacter spp. (4%). Non-intubated patients with severe HAP are often man- aged in an ICU. Management of these patients according to p rinciples laid down for VAP is often appropriate. AUTHOR \200\231S TIP Negative microbiology may be the due to antibiotic treatment in the pr eceding 72 hours. Therefore in patients who have recently received antibiotics, the sus- pe cted diagnosis of HAP cannot be refuted based on negative microbiology. Microbiological diagnosis \200 \200 Most of the data are from VAP. Differentiating between colonization and infection is dif- \201 cult. Colonization of the trachea precedes pneumonia in almost all cases of VAP. Quan titative cultures of lower respiratory tract samples have been used to define both pneumoni a and the pathogen involved. Specialized laboratory skills are necessary. Different techniq ues (protected specimen brushing, BAL) have different thresholds for diagnosing infection ( as opposed to colonization). Diagnostic accuracy varies widely. AUTHOR \200\231S TIP When applying recommendations relating to \200\230HAP in general \200 \231 to patients with \200\230HAP other than VAP \200\231, be aware of the patient groups from which the primary data were derived. Epidemiology HAP \200 \200 HAP affects 0.5 to 1.7% of patients admitted to hospital. It increases length of stay (LOS) by 7 to 9 days and is the most common nosocomial infection contributing to death. CHAPTER 8.2 Hospital-acquired pneumonia 173 Blind lavage is a simple and effective method to obtain LRT samples and to identify potenti al pathogens. Endotracheal aspirates are not recommended for the diagnosis of VAP due to lo w speci \201 city. MDR Klebsiella, Serratia, Enterobacter and Acinetobacter spp. often retain susceptibility t o carbapenams. MDR Gram-positive pathogens \200 MRSA is an enlarging problem in many ICUs. Within ICUs in the US, MRSA is identi \201 ed i n up to 59% of patients with nosocomial Staph. aureus infection. Most MRSA isolates remain susceptible to vancomycin and linezolid although resistance to these antibiotics has been d escribed. Microbiology In early-onset HAP (ie. occurring less than 5 days from admission), the predom inant organisms implicated are: \200 \200 \200 \200 Streptococcus pneumoniae Haemophilus in \202 uenzae Methicillin-sensitive Staphylococcus a ureus (MSSA) Antibiotic sensitive Gram-negative pathogens such as Klebsiella pneumoniae, Es cherichia coli, Enterobacter spp., Proteus spp., Serratia marcesens. In late-onset HAP (occ urring 5 days after admission), multi-drug resistant (MDR) pathogens are common. Viral and fungal pathogens are uncommon as causes of HAP in immunocompetent patients. Further reading Baraibar J, Correa H, Mariscal D, et al. Risk factors for infection by Acin etobacter baumannii in intubated patients with nosocomial pneumonia. Chest 1997; 112(4): 10 50 \200\2234. Craven DE. Epidemiology of ventilator-associated pneumonia. Chest 2000; 117(4 Suppl 2): 186S \200\223187S. Chastre J, Trouillet JL. Problem pathogens (Pseudomonas aeruginosa and Acinetobacter). Semi n Respir Infect 2000; 15(4): 287 \200\22398. MDR pathogens \200 Fabregas N, Ewig S, Torres A, et al. Clinical diagnosis of ventilator associated pneumonia revisited: comparative validation using immediate post-mortem lung biopsies. Thorax 1999; 5 4(10): 867 \200\22373. HAP caused by MDR pathogens is associated with increased mortality compared to pneumonia ca used by non-MDR pathogens. Risk factors for infection by MDR pathogens in general include p rior use of antibiotics, an immunocompromised state, and late-onset HAP. Pseudomonas aerugi nosa, Methicillin-resistant Staph aureus (MRSA), Acinetobacter baumannii and Extended Spect rum Beta Lactamase (ESBL) producing Klebsiella pneumoniae are the main pathogens. One study found that up to 57% of patients with VAP had \200\230potentially resistant \200\231 path ogens. However, these \201 gures cannot be generalized as resistance patterns vary betwee n units. Guidelines for the management of adults with hospital acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171(4): 388 \200\223416. Guidelines for the management of hospital-acquired pneumonia in the UK: Report of the worki ng Party as Hospital-Acquired Pneumonia of the British Society for Antimicrobial Chemothera py. JAC 2008; 62: 5 \200\22334. Lim WS, Macfarlane JT. A prospective comparison of nursing home acquired pneumonia with com munity acquired pneumonia Eur Respir J 2001; 18: 362 \200\223368. Luna CM, Blanzaco D, Niederman MS, et al. Resolution of ventila- tor-associated pneumonia: prospective evaluation of the clinical pulmonary infection score as an early clinical predi ctor of out- come. Crit Care Med 2003; 31(3): 676 \200\22382. MDR Gram-negative pathogens \200 National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October 2004. Am J Infect Control 2004; 32(8): 470 \200\223 85. Pseudomonas aeruginosa is the commonest MDR pathogen in many units. Risk factors for acquir ing Ps aeruginosa infection include the presence of ARDS, underlying COPD, prolonged mechan ical ventilation and extended stay on ICU. Some isolates of Ps aeruginosa are susceptible o nly to polymyxin B (ie. resistant to aminoglycosides, cepha- losporins, fluoroquinolones an d antipseudomonal penicillins). Risk factors for Acinetobacter spp. infection include recen t head trauma or neurosurgery, presence of ARDS and large-volume aspiration. Safdar N, Dezfulian C, Collard HR, et al. Clinical and economic consequences of ventilator- associated pneumonia: a systematic review. Crit Care Med 2005; 33(10): 2184 \200\22393. Sopena N, Sabria M. Multicenter study of hospital-acquired pneu- monia in non-ICU patients. Chest 2005; 127(1): 213 \200\223219. W-S LIM 174 8.2 \200\223 continued Hospital-acquired pneumonia: prevention and treatment Prevention How does HAP arise? HAP to occur microbial pathogens \201 rst need to enter an d then colonize the lower respiratory tract (LRT). Host defenses must then be overcome befo re invasion and infection can ensue. Aspiration of oropharyngeal pathogens represents the m ain route by which bacteria enter the LRT. Oropharyngeal colonization by Gram-negative path ogens upon hospital admission is an independent risk factor for the develop- ment of HAP. General strategies to prevent HAP Most of the strategies that have been studied relate to V AP. \200 Avoid intubation and mechanical ventilation. Consider non-invasive ventilation. In intubate d patients, reduce the likelihood of aspiration of oropharyngeal pathogens by (a) maintaini ng endotra- cheal tube cuff pressures between 25 \200\22330cm water and (b) limiting the us e of sedatives and paralytic agents which depress cough. Avoid nursing the patient in a sup ine position. In one RCT, the risk of HAP was decreased 3-fold when ICU patients were manag ed in the semi-recumbent position (30 \200\22345 ) compared to the supine position. Enco urage oral feeding whenever possible. Enteral feed- ing increases the risk of aspiration of gastric contents although a clear association with HAP has not been demonstrated. If nutri tional supplementation is required, enteral feeding carries fewer risks than parenteral fee ding. Fig. 8.2.1 MRSA pneumonia in a patient on ICU. SDD has been less effective. Many units remain concerned regarding the selection of MDR pat hogens through the routine adoption of SDD. Antibiotic treatment: principles \200 Antibiotic choices are based on the likelihood of MDR pathogens causing the episode of HAP being treated and not based on the severity of disease. Locally relevant microbiological da ta relating to (a) the range of potential pathogens and (b) antimicrobial resistance patter ns are essential to guide local empirical antibiotic choices. A 7-day course of antibiotics is usually adequate unless the patient is not responding to treatment. AUTHOR \200\231S TIP A high standard of infection control (e.g. hand washing) is as importa nt as other measures through reducing environmental sources of infection and the transfer o f pathogens between staff and patients. Importance of optimal empirical treatment Inappropriate empirical antibiotic therapy in ICU patients with nosocomial pneumonia has been shown to be associated with increased mortalit y in various studies. This excess mortality is evident despite antibiotic switching accordi ng to microbiology results, emphasizing the importance of optimal treatment from the outset in these already critically ill patients. Advocates of broad spectrum combination antibiot ics as \201 rst-line empirical therapy, instead of second-line therapy as traditionally e mployed cite reasons related to: \200 \200 Stress bleeding prophylaxis and HAP Antihistamines and antacids are associated with an incr eased risk of HAP in patients managed on ICUs. Sucralfate, which does not decrease intragas tric acidity nor alter gastric volume, has been associated in some trials with a lower inci dence of VAP compared to antacids or antihistamines. In one large trial, sucralfate was ass ociated with an increased risk of clinically signi \201 cant gastrointestinal bleeding com pared to antacids or antihistamines. \200 increasing antibiotic resistance; and the recognition of the importance of optimal (ie. app ropriate and early) empirical therapy. Combination therapy: effect on resistance \200 Animal studies report less emergent antibiotic resistance in Pseudomonas aeruginosa using c ombination antibiotic therapy. There are limited data from human clinical trials demonstrat ing this effect. Where stress ulcer prophylaxis is indicated, sucralfate is prefered to reduce the risk of V AP , but sucralfate should only be used in patients with low to moderate risks of bleeding. Antibiotics and selective decontamination The use of antibiotics for the selective decontam ination of the digestive tract (SDD) has been associated with decreased rates of HAP and in creased ICU survival. In ICUs with endemically high levels of antibiotic resistance, Combination therapy: effect on ef \201 cacy No clinical trial has demonstrated an improved prognosis with combination empirical antibiotic therapy versus monotherapy. CHAPTER 8.2 Hospital-acquired pneumonia 175 Further reading Bonten MJ, Bergmans DC, Ambergen AW, et al. Risk factors for pneumonia, and colonization of respiratory tract and stomach in mechanically ventilated ICU patients. Am J Respir Crit Care Med 1996; 154(5): 1339 \200\22346. Antibiotic duration and emerging resistance The emergence of MDR pathogens in the ICU is as sociated with the volume of antibiotics used. Optimizing the dura- tion of antibiotic treat ment (and hence antibiotic volume) helps limit antibiotic resistance. In a large prospectiv e study of patients with VAP in 51 ICUs in France randomized to 8 versus 15 days of antibio tics: \200 Chastre J, Wolff M, Fagon JY, et al. Comparison of 8 vs 15 days of antibiotic therapy for v entilator-associated pneumonia in adults: a randomized trial. Jama 2003; 290(19): 2588 \200 \22398. No significant differences were noted in (a) 28-day mortality (18.8% vs 17.2% respectively) or (b) microbio- logically documented recurrent pulmonary infection (28.9% vs 26% respecti vely, 2.9% difference; 90% con \201 dence interval (CI) \210\2223.2 to 9.1). MDR pathogen s were implicated less frequently when recurrent infection occurred (42% vs 62% respectivel y, p=0.038). In a subgroup of patients with Pseudomonas aeruginosa infection (a third of pa tients in each arm), recurrent pulmonary infection was more common in the 8-day group compa red to the 15-day group (40.6% vs 25.4% respectively, p=0.09). Cook D, Guyatt G, Marshall J, et al. A comparison of sucralfate and ranitidine for the prev ention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. Can adian Critical Care Trials Group. N Engl J Med 1998; 338(12): 791 \200\2237. de Jonge E, Schultz MJ, Spanjaard L, et al. Effects of selective decon- tamination of diges tive tract on mortality and acquisition of resistant bacteria in intensive care: a randomiz ed controlled trial. Lancet 2003; 362(9389): 1011 \200\2236. Drakulovic MB, Torres A, Bauer TT, et al. Supine body position as a risk factor for nosocom ial pneumonia in mechanically ventilated patients: a randomized trial. Lancet 1999; 354(919 3): 1851 \200\2238. Driks MR, Craven DE, Celli BR, et al. Nosocomial pneumonia in intubated patients given sucr alfate as compared with antacids or histamine type 2 blockers. The role of gastric coloniza tion. N Engl J Med 1987; 317(22): 1376 \200\22382. Which antibiotic to choose? Early-onset HAP, no risk factors for resistance In HAP caused b y non-MDR pathogens, monotherapy with a limited spectrum antibiotic directed against the mo st likely pathogens is adequate: \200 Gastinne H, Wolff M, Delatour F, et al. A controlled trial in intensive care units of selec tive decontamination of the digestive tract with nonabsorbable antibiotics. The French Stud y Group on Selective Decontamination of the Digestive Tract. N Engl J Med 1992; 326(9): 594 \200\2239. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171(4): 388 \200\223416. no prior antibiotics \200\223 consider co-amoxilas or cefuroxime; prior antibiotics \200 \223 consider cefotamine, ceftriacene, a \202 urosamine or pipenacillin/tazobactam. Neuhauser MM, Weinstein RA, Rydman R, et al. Antibiotic resist- ance among gram-negative ba cilli in US intensive care units: impli- cations for \202 uoroquinolone use. Jama 2003; 2 89(7): 885 \200\2238. Late-onset HAP, risk factors for resistance \200 