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The use of adjunctive inhaled antibiotics in VAP has been evaluated in several

studies. A systematic review of 16 observational studies and randomized trials

without blinding revealed that aerosolized colistin was associated with microbial

eradication (OR, 1.61; 95% CI, 1.11–2.35) and improved clinical response (OR,

1.57; 95% CI, 1.14–2.15) but the results were limited by several biases.

131 A

systematic review of 12 observational and randomized trials with some blinding

showed that nebulized antibiotics in patients with VAP had some benefit in patient

outcomes. Nebulized antibiotics were associated with increased rate of clinical cure

(RR, 1.23; 95% CI, 1.05–1.43).

132 Neither studies showed an improvement in

mortality, duration of mechanical ventilation, or length of stay in the intensive care

unit.

ALTERNATIVE DOSING OF ANTIBIOTICS FOR MULTIDRUGRESISTANT PATHOGENS

Carbapenems, cephalosporins, and extended-spectrum penicillins or β-lactamase

inhibitors demonstrate time-dependent killing, and it is known that bactericidal

killing for these drug classes is optimized if their free drug concentrations are greater

than the MIC (30%–40%, 50%–60%, and 60%–70% of the time, respectively).

Prolonged or continuous infusions have been used to increase the time that free drug

concentrations are greater than the MIC, theoretically leading to improved patient

outcomes.

133

p. 1419

p. 1420

Continuous infusions were first used in the late 1970s with suggested improvement

in clinical cure rates,

134 but until recently they were largely abandoned owing to

logistical concerns about medication stability, drug compatibility, and limited IV

access. These concerns were lessened by use of contemporary prolonged infusions.

This latter strategy is supported primarily by Monte Carlo simulation, a mathematical

modeling technique that estimates the probability of pharmacodynamic target

attainment at each MIC for a given MIC range.

Patients diagnosed with VAP and treated with cefepime (2 g every 8 hours for 3

hours) have been evaluated using Monte Carlo methodology. Investigators found that

at an MIC of 1 mcg/mL, all regimens had a probability of target attainment greater

than 90%. However, at an MIC of 8 mcg/mL, when compared with 30-minute

intermittent infusions of 1 to 2 g every 8 hours and 2 g every 12 hours, only the

prolonged infusion (3 hours) of 2 g every 8 hours maintained 90% probability of

target attainment. As one might predict, this phenomenon was only demonstrated in

patients with preserved renal function as defined as a creatinine clearance of 50 to

120 mL/minute.

135

Intermittent and continuous infusion dosing strategies have also been compared

when using piperacillin–tazobactam to treat Pseudomonas infections. Lodise et al.

136

retrospectively compared intermittent infusions of 3.375 g IV piperacillin–

tazobactam (infused over 30 minutes every 6 hours) versus extended infusions of

3.375 g IV piperacillin–tazobactam (infused over 4 hours every 8 hours). Results

indicated a shorter length of hospital stay (21 days vs. 38 days; p = 0.02) and lower

14 day mortality rate among patients with Acute Physiological and Chronic Health

Evaluation-II scores >17 (12.2% vs. 31.6%; p = 0.04) in patients receiving extended

infusion therapy.

136

Ventilator-Associated Pneumonia Prophylaxis

The substantial risk of pneumonia in the ICU has prompted aggressive methods to

prevent this disease.

137 The most important recommendations include the use of the

semi-upright position to reduce the risk of aspiration, infection control (including

hand washing) to prevent the spread of pathogens from one patient to the next, and

surveillance for ICU infections.

138

Several strategies for prevention of VAP are controversial, including selective

decontamination of the digestive tract (SDD), selective oral decontamination (SOD),

and topical antiseptics applied to the oral mucosa. These three strategies address the

concept that VAP occurs after colonization of the upper respiratory tract. Because

digestive tract flora may play a role in this colonization, the impact of various

decontamination approaches has been studied. For SDD a combination therapy

including topical tobramycin, polymixin E, and sometimes amphotericin B is

administered to the stomach and oropharynx 4 times daily in combination with IV

administration of ciprofloxacin or a second-generation cephalosporin. SOD uses a

similar antimicrobial strategy to SDD, except that the IV agents are omitted and the

combination therapy is applied to the oropharynx.

Historically, SDD and SOD are more widely used in Europe, and most of the

literature investigating these techniques in thousands of patients and supporting their

use results from outside the United States. In 2009, De Smet et al.

139 performed a

large crossover study comparing standard of care ventilation bundles versus SDD

versus SOD in mechanically ventilated patients and found a statistically reduced risk

of 28-day mortality with an OR of 0.83 (95% CI, 0.72–0.97) for SDD and 0.86 (95%

CI, 0.74–0.99) for SOD.

139

In 2015, Roquilly et al.

140 produced the largest meta-analysis of VAP prevention

techniques to decrease mortality. Over 37,000 patients were involved from 157

randomized trials. Although the overall mortality reduction was 5% in the

intervention group, in a subgroup analysis, only SDD significantly decreased

mortality compared to control with a RR of 0.84 (95% CI, 0.76–0.92).

140 Despite the

overwhelming evidence supporting SDD, leading clinicians suggest there are still

concerns of North American practitioners who fear that widespread use of antibiotics

for SDD will increase antibiotic resistance and Clostridium difficile infections,

particularly in the United States where drug resistance is more prevalent than in

Northern Europe.

141

KEY REFERENCES AND WEBSITES

A full list of references for this chapter can be found at

http://thepoint.lww.com/AT11e. Below are the key references and websites for this

chapter, with the corresponding reference number in this chapter found in parentheses

after the reference.

Key References

Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice

Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Inf Dis.

2016;63;1-51. (49)

Braman SS. Chronic cough due to acute bronchitis: ACCP evidence-based practice guidelines. Chest. 2006;129(1,

suppl):95S. (3)

CDC. Prevention of pneumococcal disease: recommendations from the Advisory Committee on Immunization

Practices (ACIP). MMWR Recomm Rep. 1997;46(RR-8):1.

Criner GJ et al. Prevention of acute exacerbation of COPD. American College of Chest Physicians and Canadian

Thoracic Society Guideline. Chest. 2015;147:883. (17)

Gonzales R et al. Principles of appropriate antibiotic use for treatment of acute respiratory tract infections in adults:

background. Ann Intern Med. 2001;134:521. (7)

Smith SM et al. Antibiotics for acute bronchitis. Cochrane Database Syst Rev. 2014;(3):CD000245. (8)

Quon BS et al. Contemporary management of acute exacerbations of COPD: a systemic review and metaanalysis. Chest. 2008;133: 756. (18)

Harper SA et al. Seasonal influenza in adults and children: diagnosis, treatment, chemoprophylaxis, and institutional

outbreak management: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect

Dis. 2009;48:1003. (38)

Mandell LA et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the

management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44(Suppl 2):S27. (32)

Key Websites

Centers for Disease Control and Prevention. Seasonal Influenza Vaccination Resources for Health Professionals.

http://www.cdc.gov/flu/professionals/vaccination/.

From the Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic

Lung Disease (GOLD) 2017. Available from: http://goldcopd.org/”http://goldcopd.org. Accessed June 17,

2017. (17)

COMPLETE REFERENCES CHAPTER 67 RESPIRATORY

TRACT INFECTIONS

Albert RH. Diagnosis and treatment of acute bronchitis. Am Fam Physician. 2010;82:1345.

Wenzel RP, Fowler AA 3rd. Clinical practice. Acute bronchitis. N EnglJ Med. 2006;355:2125.

Braman SS. Chronic cough due to acute bronchitis: ACCP evidence-based practice guidelines. Chest. 2006;129(1,

Suppl):103S.

NationalAmbulatory Medical Care Survey and National HospitalAmbulatory Medical Care Survey: 2009–2010

Combined Year Tables. http://www.cdc.gov/nchs/data/ahcd/combined_tables/2009-

2010_combined_web_table01.pdf.

Clark TW et al. Adults hospitalized with acute respiratory illness rarely have detectable bacteria in the absence

of COPD or pneumonia; viral infection predominates in a large prospective UK sample. J Infect. 2014;69:507.

Snow V et al. Principles of appropriate antibiotic use for treatment of acute bronchitis in adults. Ann Intern Med.

2001;134:518.

Gonzales R et al. Principles of appropriate antibiotic use for treatment of acute respiratory tract infections in adults:

background. Ann Intern Med. 2001;134:521.

Smith SM et al. Antibiotics for acute bronchitis. Cochrane Database Syst Rev. 2014;(3):CD000245.

Tan T et al. Antibiotic prescribing for self-limiting respiratory tract infections in primary care:summary of NICE

guidance. BMJ. 2008;337:a437.

Barnett ML, Linder JA. Antibiotic prescribing for adults with acute bronchitis in the United States, 1996–2010.

JAMA. 2014;311:2020.

Smith SM et al. Over-the-counter (OTC) medications for acute cough in children and adults in community

settings. Cochrane Database Syst Rev. 2014;(11):CD001831.

Becker LA et al. Beta2-agonists for acute bronchitis. Cochrane Database Syst Rev. 2011;(7):CD001726.

Schuetz P et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane

Database Syst Rev. 2012;(9): CD007498.

Pfister R et al. Procalcitonin for diagnosis of bacterial pneumonia in critically ill patients during 2009 H1N1

influenza pandemic: a prospective cohort study, systematic review, and individual patient data meta-analysis.

Crit Care. 2014;18:R44.

El-Gohary M et al. Corticosteroids for acute and subacute cough following respiratory tract infection: a systemic

review. Fam Pract. 2013;30:492

From the Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic

Lung Disease (GOLD) 2017. Available from: http://goldcopd.org. Accessed June 17, 2017.

Criner GJ et al. Prevention of acute exacerbation of COPD. American College of Chest Physicians and Canadian

Thoracic Society Guideline. Chest. 2015;147:883.

Quon BS et al. Contemporary management of acute exacerbations of COPD: a systemic review and

metaanalysis. Chest. 2008;133:756.

Sethi S. Infectious etiology of acute exacerbations of chronic bronchitis. Chest. 2000;117(5, Suppl 2):380S.

Sethi S, Murphy TF. Infection in the pathogenesis and course of chronic obstructive pulmonary disease. N EnglJ

Med. 2008;359:2355.

Rosell A et al. Microbiologic determinants of exacerbation in chronic obstructive pulmonary disease. Arch Intern

Med. 2005;165:891.

Soler N et al. Bronchoscopic validation of the significance of sputum purulence in severe exacerbations of chronic

obstructive pulmonary disease. Thorax. 2007;62:29.

Anthonisen NR et al. Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann Intern

Med. 1987;106:196.

Vollenweider DJ et al. Antibiotics for exacerbations of chronic obstructive pulmonary disease. Cochrane

Database Syst Rev. 2012;(12):CD010257.

Walters JA et al. Systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease.

Cochrane Database Syst Rev. 2014;(9):CD001288.

Walters JA et al. Different durations of corticosteroid therapy for exacerbations of chronic obstructive pulmonary

disease. Cochrane Database Syst Rev. 2014;(12):CD006897.

Rutschmann OT et al. Should pulmonary embolism be suspected in exacerbation of chronic obstructive pulmonary

disease? Thorax. 2007;62:121.

Jain S et al. Community-acquired pneumonia requiring hospitalization among U.S. adults. N Engl J Med.

2015;373(5):415–427. DOI: 10.1056/NEJMoa1500245

Jain S et al. Community-acquired pneumonia requiring hospitalization among U.S. children. N Engl J Med.

2015;373(9):835–845.

Yu H et al. Clinical and economic burden of community-acquired pneumonia in the Medicare fee-for-service

population. J Am Geriatr Soc. 2012;60(11):2137–2143.

Corrales-Medina VF et al. Cardiac complications in patients with community-acquired pneumonia: a systematic

review and meta-analysis of observationalstudies. PLoS Med. 2011;8(6):e1001048.

Mandell LA et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on

the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44(Suppl 2):S27.

Halm EA, Teirstein AS. Clinical practice. Management of community-acquired pneumonia. N Engl J Med.

2002;347:2039.

Laterre PF et al. Severe community-acquired pneumonia as a cause of severe sepsis: data from the PROWESS

study. Crit Care Med. 2005;33:952.

Fine MJ et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. N EnglJ Med.

1997;336:243.

Lim WS et al. Defining community acquired pneumonia severity on presentation to hospital: an international

derivation and validation study. Thorax. 2003;58:377.

Aujesky D et al. Prospective comparison of three validated prediction rules for prognosis in community-acquired

pneumonia. Am J Med. 2005;118:384.

Harper SA et al. Seasonal influenza in adults and children: diagnosis, treatment, chemoprophylaxis, and

institutional outbreak management: clinical practice guidelines of the Infectious Diseases Society of America.

Clin Infect Dis. 2009;48:1003.

Kadioglu A et al. The role of Streptococcus pneumoniae virulence factors in host respiratory colonization and

disease. Nat Rev Microbiol. 2008;6:288.

van der Poll T, Opal SM. Pathogenesis, treatment, and prevention of pneumococcal pneumonia. Lancet.

2009;374:1543.

Pelton SI et al. Risk of pneumococcal disease in children with chronic medical conditions in the era of

pneumococcal conjugate vaccine. Clin Infect Dis. 2014;59(5):615–623.

Arnold FW et al. A worldwide perspective of atypical pathogens in community-acquired pneumonia. Am J Respir

Crit Care Med. 2007;175(10):1086–1093.

Lieberman D et al. Multiple pathogens in adult patients admitted with community-acquired pneumonia: a one year

prospective study of 346 consecutive patients. Thorax. 1996;51:179.

Tessmer A et al. Impact of intravenous β-lactam/macrolide versus β-lactam monotherapy on mortality in

hospitalized patients with community-acquired pneumonia. J Antimicrob Chemother. 2009;63:1025.

Martin-Loeches I et al. Combination antibiotic therapy with macrolides improves survival in intubated patients

with community-acquired pneumonia. Intensive Care Med. 2010;36:612.

Dudas V et al. Antimicrobialselection for hospitalized patients with presumed community-acquired pneumonia: a

survey of nonteaching US community hospitals. Ann Pharmacother. 2000;34:446.

Restrepo MI et al. Impact of macrolide therapy on mortality for patients with severe sepsis due to pneumonia.

Eur Respir J. 2009;33:153.

Fiumefreddo R et al. Clinical predictors for Legionella in patients presenting with community-acquired pneumonia

to the emergency department. BMC Pulm Med. 2009;9:4.

Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice

Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Inf Dis.

2016;63;1–51.

Hageman JC et al. Severe community-acquired pneumonia due to Staphylococcus aureus, 2003–04 influenza

season. Emerg Infect Dis. 2006;12:894.

Gillet Y et al. Association between Staphylococcus aureus strains carrying gene for Panton-Valentine leukocidin

and highly lethal necrotising pneumonia in young immunocompetent patients. Lancet. 2002;359:753.

Rasigade JP et al. Global distribution and evolution of Panton-Valentine leukocidin-positive methicillin-susceptible

Staphylococcus aureus, 1981–2007. J Infect Dis. 2010;201:1589.

Taneja C et al. Clinical and economic outcomes in patients with community-acquired Staphylococcus aureus

pneumonia. J Hosp Med. 2010;5:528.

Jennings LC et al. Incidence and characteristics of viral community-acquired pneumonia in adults. Thorax.

2008;63:42.

Johnstone J et al. Viral infection in adults hospitalized with community-acquired pneumonia: prevalence,

pathogens, and presentation. Chest. 2008;134:1141.

Lieberman D et al. Respiratory viruses in adults with community-acquired pneumonia. Chest. 2010;138:811.

Meehan TP et al. Quality of care, process, and outcomes in elderly patients with pneumonia. JAMA.

1997;278:2080.

Houck PM et al. Timing of antibiotic administration and outcomes for Medicare patients hospitalized with

community-acquired pneumonia. Arch Intern Med. 2004;164:637.

Farrell DJ et al. Distribution and antibacterial susceptibility of macrolide resistance genotypes in Streptococcus

pneumoniae: PROTEKT Year 5 (2003–2004). Int J Antimicrob Agents. 2008;31:245.

Hakenbeck R et al. Penicillin-binding proteins in beta-lactam-resistant Streptococcus pneumoniae. Microb Drug

Resist. 1999;5:91.

Pallares R et al. The effect of cephalosporin resistance on mortality in adult patients with nonmeningealsystemic

pneumococcal infections. Am J Med. 2002;113:120.

Yu VL et al. An international prospective study of pneumococcal bacteremia: correlation with in vitro resistance,

antibiotics administered, and clinical outcome. Clin Infect Dis. 2003;37:230.

Lynch JP 3rd, Zhanel GG. Escalation of antimicrobial resistance among Streptococcus pneumoniae: implications

for therapy. Semin Respir Crit Care Med. 2005;26:575.

Arnold FW et al. Improving outcomes in elderly patients with community-acquired pneumonia by adhering to

national guidelines: Community-Acquired Pneumonia Organization International cohort study results. Arch

Intern Med. 2009;169:1515.

McCabe C et al. Guideline-concordant therapy and reduced mortality and length of stay in adults with communityacquired pneumonia: playing by the rules. Arch Intern Med. 2009;169:1525.

Aliberti S et al. Duration of antibiotic therapy in hospitalised patients with community-acquired pneumonia. Eur

Respir J. 2010;36:128.

LiJZ et al. Efficacy of short-course antibiotic regimens for community-acquired pneumonia: a meta-analysis. Am

J Med. 2007;120(9):783–790.

Christ-Crain M et al. Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized

trial. Am J Respir Crit Care Med. 2006;174:84.

Brankston G et al. Transmission of influenza A in human beings. Lancet Infect Dis. 2007;7:257.

Cowling BJ et al. Comparative epidemiology of pandemic and seasonal influenza A in households. N EnglJ Med.

2010;362:2175.

Carrat F et al. Time lines of infection and disease in human influenza: a review of volunteer challenge studies. Am

J Epidemiol. 2008;167:775.

Lee N et al. Viral loads and duration of viral shedding in adult patients hospitalized with influenza. J Infect Dis.

2009;200:492.

Giannella M et al. Prolonged viral shedding in pandemic influenza A(H1N1): clinical significance and viral load

analysis in hospitalized patients. Clin Microbiol Infect. 2011;17(8):1160–116.5

Englund JA et al. Common emergence of amantadine- and rimantadine-resistant influenza A viruses in

symptomatic immunocompromised adults. Clin Infect Dis. 1998;26:1418.

Boivin G et al. Prolonged excretion of amantadine-resistant influenza A virus quasi species after cessation of

antiviral therapy in an immunocompromised patient. Clin Infect Dis. 2002;34:E23.

McGeer A et al. Antiviral therapy and outcomes of influenza requiring hospitalization in Ontario, Canada. Clin

Infect Dis. 2007;45:1568.

Lee N et al. Outcomes of adults hospitalised with severe influenza. Thorax. 2010;65:510.

Stephenson I et al. Neuraminidase inhibitor resistance after oseltamivir treatment of acute influenza A and B in

children. Clin Infect Dis. 2009;48:389.

Dharan NJ et al. Infections with oseltamivir-resistant influenza A(H1N1) virus in the United States. JAMA.

2009;301:1034.

Kidd IM et al. H1N1 pneumonitis treated with intravenous zanamivir. Lancet. 2009;374:1036.

Gaur AH et al. Intravenous zanamivir for oseltamivir- resistant 2009 H1N1 influenza. N EnglJ Med. 2010;362:88.

Alp E et al. Incidence, risk factors and mortality of nosocomial pneumonia in intensive care units: a prospective

study. Ann Clin Microbiol Antimicrob. 2004;3:17.

Kollef M et al. Epidemiology and outcomes of health-care- associated pneumonia: results from a large US

database of culture-positive pneumonia [published correction appears in Chest. 2006;129:831]. Chest.

2005;128:3854.

Cameron JL et al. Aspiration in patients with tracheostomies. Surg Gynecol Obstet. 1973;136:68.

Valles J et al. Continuous aspiration of subglottic secretions in preventing ventilator-associated pneumonia. Ann

Intern Med. 1995;122:179.

Tablan OC et al. Guidelines for preventing health-care-associated pneumonia, 2003: recommendations of CDC

and the Healthcare Infection Control Practices Advisory Committee. MMWR Recomm Rep. 2004;53(RR-3):1.

Bonten M 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;154:1339.

Raoof S et al. An official multi-society statement: ventilator-associated events: the new definition. Chest.

2014;145:10.

Luna CM et al. Blood cultures have limited value in predicting severity of illness and as a diagnostic tool in

100.

101.

102.

103.

104.

105.

106.

107.

108.

109.

110.

111.

112.

113.

114.

115.

116.

117.

ventilator-associated pneumonia. Chest. 1999;116:1075.

Johanson WG Jr et al. Nosocomial respiratory infections with gram-negative bacilli: the significance of

colonization of the respiratory tract. Ann Intern Med. 1972;77:701.

Tillotson JR, Finland M. Bacterial colonization and clinical super-infection of the respiratory tract complicating

antibiotic treatment of pneumonia. J Infect Dis. 1969;119:597.

Rouby JJ et al. Nosocomial bronchopneumonia in the critically ill: histologic and bacteriologic aspects. Am Rev

Respir Dis. 1992;146:1059.

Bartlett JG et al. Bacteriology of hospital-acquired pneumonia. Arch Intern Med. 1986;146:868.

Prod’hom G et al. Nosocomial pneumonia in mechanically ventilated patients receiving antacid, ranitidine, or

sucralfate as prophylaxis for stress ulcer: a randomized controlled trial. Ann Intern Med. 1994;120:653.

Rello J et al. Impact of previous antimicrobial therapy on etiology and outcome of ventilator-associated

pneumonia. Chest. 1993;104:1230.

Fridkin SK et al. Magnitude and prevention of nosocomial infections in the intensive care unit. Infect Dis Clin

North Am. 1997;11:479.

Jones R. Microbial etiologies of hospital-acquired bacterial pneumonia and ventilator-associated bacterial

pneumonia. Clin Infect Dis. 2010;51:1114.

Edelstein PH. Legionnaires’ disease. Clin Infect Dis. 1993;16:74.

Rhame FS. Prevention of nosocomial aspergillosis. J Hosp Infect. 1991;18(Suppl A):466.

Maruyama T et al. A new strategy for healthcare-associated pneumonia: a 2 year prospective multicenter cohort

study using risk factors for multidrug-resistant pathogens to select initial empiric therapy. Clin Infect Dis.

2013;57:1373.

Muscroft TJ et al. The microflora of the postoperative stomach. Br J Surg. 1981;68:560.

du Moulin GC et al. Aspiration of gastric bacteria in antacid-treated patients: a frequent cause of postoperative

colonisation of the airway. Lancet. 1982;1:242.

Eom CS et al. Use of acid-suppressive drugs and risk of pneumonia: systematic review and meta-analysis.

CMAJ. 2011;183:310.

Herzig SJ et al. Acid-suppressive medication use and the risk for hospital-acquired pneumonia. JAMA.

2009;301:2120.

Chow JW et al. Enterobacter bacteremia: clinical features and emergence of antibiotic resistance during

therapy. Ann Intern Med. 1991;115:585.

Medeiros AA. Relapsing infection due to Enterobacter species: lessons of heterogeneity. Clin Infect Dis.

1997;25:341.

Acar J. Rapid emergence of resistance to cefepime during treatment. Clin Infect Dis. 1998;26:1484.

Garnacho-Montero J et al. Treatment of multidrug-resistant Acinetobacter baumannii ventilator-associated

pneumonia (VAP) with intravenous colistin: a comparison with imipenem-susceptible VAP. Clin Infect Dis.

2003;36:1111.

Smolyakov R et al. Nosocomial multi-drug resistant Acinetobacter baumannii bloodstream infection: risk factors

and outcome with ampicillin-sulbactam treatment. J Hosp Infect. 2003;54:32.

Liu C et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of

methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52:285.

Rybak M et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American

Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of

Infectious Diseases Pharmacists. Am J Health Syst Pharm. 2009;66:82.

Jeffres MN et al. Predictors of mortality for methicillin-resistant Staphylococcus aureus health-care-associated

pneumonia:specific evaluation of vancomycin pharmacokinetic indices. Chest. 2006;130:947.

Conte JE Jr et al. Intrapulmonary pharmacokinetics of linezolid. Antimicrob Agents Chemother. 2002;46:1475.

Rubinstein E et al. Linezolid (PNU-100766) versus vancomycin in the treatment of hospitalized patients with

nosocomial pneumonia: a randomized, double-blind, multicenter study. Clin Infect Dis. 2001;32:402.

Wunderink RG et al. Continuation of a randomized, double-blind, multicenter study of linezolid versus

vancomycin in the treatment of patients with nosocomial pneumonia. Clin Ther. 2003;25:980.

Wunderink RG et al. Linezolid vs vancomycin: analysis of two double-blind studies of patients with methicillinresistant Staphylococcus aureus nosocomial pneumonia. Chest. 2003;124:1789.

Walkey AJ et al. Linezolid vs glycopeptide antibiotics for the 5 treatment of suspected methicillin-resistant

Staphylococcus aureus nosocomial pneumonia: a meta-analysis of randomized controlled trials. Chest.

2011;139:1148.

118.

119.

120.

121.

122.

123.

124.

125.

126.

127.

128.

129.

130.

131.

132.

133.

134.

135.

136.

137.

138.

139.

140.

141.

Wunderink RG et al. Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a

randomized, controlled study. Clin Infect Dis. 2012;54:621.

Chastre J et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a

randomized trial. JAMA. 2003;290:2588.

Freire AT et al. Comparison of tigecycline with imipenem/cilastatin for the treatment of hospital-acquired

pneumonia. Diagn Microbiol Infect Dis. 2010;68:140.

Torres A et al. Analysis of Phase 3 telavancin nosocomial pneumonia data excluding patients with severe renal

impairment and acute renal failure. J Antimicrob Chemother. 2014;69:1119.

Barza M et al. Predictability of blood levels of gentamicin in man. J Infect Dis. 1975;132:165.

Zaske DE et al. Wide interpatient variations in gentamicin dose requirements for geriatric patients. JAMA.

1982;248:3122.

Flint LM et al. Serum level monitoring of aminoglycoside antibiotics. Limitations in intensive care unit-related

bacterial pneumonia. Arch Surg. 1985;120:99.

Moore RD et al. Association of aminoglycoside plasma levels with therapeutic outcome in gram-negative

pneumonia. Am J Med. 1984;77:657.

Bergogne-Berezin E. Pharmacokinetics of antibiotics in respiratory secretion. In: Pennington JE, ed. Respiratory

Infections: Diagnosis and Management. New York, NY: Raven Press; 1983.

Bodem CR et al. Endobronchial pH. Relevance of aminoglycoside activity in gram-negative bacillary pneumonia.

Am Rev Respir Dis. 1983;127:39.

Vaudaux P. Peripheral inactivation of gentamicin. J Antimicrob Chemother. 1981;8(Suppl A):17.

Levy J et al. Bioactivity of gentamicin in purulent sputum from patients with cystic fibrosis or bronchiectasis:

comparison with activity in serum. J Infect Dis. 1983;148:1069.

Mendelman PM et al. Aminoglycoside penetration, inactivation, and efficacy in cystic fibrosis sputum. Am Rev

Respir Dis. 1985;132:761.

Valachis A et al. The role of aerosolized colistin in the treatment of ventilator-associated pneumonia: a

systematic review and meta-analysis. Crit Care Med. 2015;43:527.

Zampieri F et al. Nebulized antibiotics for ventilator-associated pneumonia: a systematic review and metaanalysis. Crit Care. 2015;19:150.

Drusano GL. Antimicrobial pharmacodynamics: critical interactions of ‘bug and drug’. Nat Rev Microbiol.

2004;2:289.

Bodey GP et al. A randomized study of carbenicillin plus cefamandole or tobramycin in the treatment of febrile

episodes in cancer patients. Am J Med. 1979;67:608.

Nicasio AM et al. Population pharmacokinetics of high-dose, prolonged-infusion cefepime in adult critically ill

patients with ventilator-associated pneumonia. Antimicrob Agents Chemother. 2009;53:1476.

Lodise T et al. Piperacillin-tazobactam for Pseudomonas aeruginosa infection: clinical implications of an

extended-infusion dosing strategy. Clin Infect Dis. 2007;44:357.

Kollef MH. The prevention of ventilator associated pneumonia. N EnglJ Med. 1999;340:627.

Torres A et al. Pulmonary aspiration of gastric contents in patients receiving mechanical ventilation: the effect of

body position. Ann Intern Med. 1992;116:540.

De Smet et al. Decontamination of the digestive tract and oropharynx in ICU patient. N Engl J Med.

2009;360:20.

Roquilly et al. Pneumonia prevention to decrease mortality in intensive care unit: a systematic review and metaanalysis. Clin Infect Dis. 2015;60:1449.

Klompas M. Editorial commentary: Evidence vs instinct for pneumonia prevention in hospitalized patients. Clin

Infect Dis. 2015;60:76.

p. 1420

Tuberculosis is an infectious disease caused by Mycobacterium

tuberculosis, and the most common site of infection is the lungs. Active

disease is characterized by fever, chills, cough, night sweats, weight

loss, and changes on chest radiography. Several risk factors for

tuberculosis have been identified, including immune suppression,

exposure to close contacts, and smoking.

Case 68-1 (Questions 1, 2)

Diagnosis of active disease includes tuberculin skin testing, chest

radiography, and sputum collection for acid-fast bacillistain and culture.

Nucleic acid amplification tests and interferon-γ release assays may aid

in the diagnosis of tuberculosis. Human immunodeficiency virus (HIV)

screening is recommended for all patients with tuberculosis.

Case 68-1 (Questions 3–7)

The goals of therapy include cure and prevention of transmission of M.

tuberculosis. Treatment of active pulmonary disease requires

administration of multiple-drug therapy for a minimum of 26 weeks.

Directly observed therapy is a core management strategy for all patients

to ensure adherence to therapy.

Case 68-1 (Questions 8–13)

Patients should be monitored for resolution of symptoms and questioned

about the occurrence of adverse events, especially hepatitis. Sputum

smears and cultures should be obtained every 2 to 4 weeks initially and

then monthly after cultures become negative. If treatment failure

occurs, three new drugs should be added to the treatment regimen.

Case 68-1 (Questions 14, 15)

Patients with latent tuberculosis infection have a positive tuberculin skin

test or interferon-γ release assay but no clinicalsymptoms or

radiographic evidence of active disease. Isoniazid for 6 to 9 months is

preferred, and rifampin for 4 months and weekly isoniazid plus

rifapentine for 12 weeks are alternatives.

Case 68-2 (Questions 1, 2)

Adverse events associated with isoniazid include hepatotoxicity and

peripheral neuropathy. Rifampin is associated with hepatotoxicity, flulike syndrome, thrombocytopenia, and discoloration of body fluids.

Pyrazinamide can cause hepatotoxicity and increased uric acid, whereas

ethambutol can cause optic neuritis.

Case 68-3 (Questions 1–3),

Case 68-4 (Question 1)

The case rate for tuberculosis in the elderly is greater than that in all

other age-groups. Principles of treatment of tuberculosis in the elderly

Case 68-5 (Question 1)

are the same as those for other age-groups.

Multidrug-resistant tuberculosis can develop as a result of nonadherence

to treatment. Successful treatment of multidrug-resistant tuberculosis is

possible depending on the host, adherence to therapy, and the number of

drugs to which the organism remains susceptible. Treatment with six to

seven drugs may be required in the intensive phase.

Case 68-6 (Questions 1, 2)

HIV infection is an important risk factor for tuberculosis. The clinical

manifestations in HIV-infected persons will vary depending on the

severity of immunodeficiency at presentation. Principles and

recommendations for treatment of active disease and latent infection in

HIV-infected persons are the same as those for HIV-negative persons.

Case 68-7 (Questions 1–3),

Case 68-8 (Question 1)

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p. 1422

In antiretroviral-naïve patients, the optimal timing for initiating

antiretroviral therapy is dependent on the patient’s CD4

+

cell count.

Antiretroviral therapy may be delayed to decrease the potential for

immune reconstitution inflammatory syndrome. If patients are receiving

antiretroviral therapy, treatment of tuberculosis should begin

immediately with modification of antiviral therapy as needed.

Case 68-7 (Questions 4, 5)

Treatment of active disease in pregnant women is the same as that for

nonpregnant women. Pyrazinamide is not recommended in pregnancy

due to insufficient safety data. The minimum duration of therapy is 9

months.

Case 68-9 (Question 1)

Infants and children have a higher risk of disseminated tuberculosis, and

treatment should be initiated promptly. Ethambutol is generally avoided

because it is difficult to assess visual acuity in children. Many experts

prefer to initiate therapy in children with three drugs and treat for a

minimum duration of 6 months.

Case 68-10 (Question 1)

Extrapulmonary tuberculosis may require longer durations of therapy.

Tuberculous meningitis may require 9 to 12 months of therapy, and

corticosteroids reduce sequelae and improve survival.

Case 68-11 (Question 1)

HISTORY

Tuberculosis (TB) is an ancient disease with evidence of spinal TB in preColumbian and early Egyptian remains. TB emerged as a major health problem in the

17th and 18th centuries when crowded living conditions of the industrial revolution

contributed to its epidemic spread throughout Europe and the United States. Early

physicians referred to TB as phthisis, derived from the Greek term for wasting,

because its clinical presentation consisted of weight loss, cough, fevers, and

hemoptysis. The etiologic agent was identified in 1882 when Robert Koch isolated

and cultured Mycobacterium tuberculosis and demonstrated its infectious nature.

With this knowledge, early treatment in the mid-1800s to the early 1900s consisted of

placing patients with TB in a sanatorium for bed rest and fresh air. With the advent of

radiographic film, pulmonary cavitary lesions were found to be a pivotal component

in the evolution of the disease. Therapy included pneumoperitoneum, thoracoplasty,

and plombage to reduce the size of the cavitary lesion, and some of these therapies

are still used today for severe and refractory cases.

The modern era of medical TB therapy began in 1944 with the discovery of

streptomycin and, shortly thereafter, p-aminosalicylic acid. Addition of isoniazid in

1952 and rifampin in the late 1960s greatly increased treatment success and provided

hope for the eventual elimination of TB. However, multidrug-resistant TB (MDRTB) emerged in the 1990s as a threat to the control of TB in the United States and

other countries.

1–3

In the subsequent decade, published reports described the

worldwide emergence of extensively drug-resistant TB (XDR-TB)

4–6 and, more

recently, the emergence of totally drug-resistant (TDR) or super XDR-TB strains.

7

Because TB strains become increasingly resistant to currently available agents, the

likelihood of achieving global control and elimination of this disease are diminished.

Therefore, a high index of suspicion for TB, rapid pathogen identification,

susceptibility testing, patient isolation, and appropriate antimicrobial therapy are

critical to prevent further development and spread of drug-resistant TB.

Incidence and Epidemiology

Assuming lifelong infection, approximately 2.0 billion people (30% of the world’s

population) are infected with M. tuberculosis.

8 TB is the second most common

causes of death from an infectious disease in the world after human

immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS).

Globally, there were an estimated 9 million new cases of TB in 2013; the majority of

these new cases were identified in the Southeast Asia, Western Pacific, and the

African regions.

9 The countries with the largest number of new cases were India,

China, Nigeria, and Pakistan.

9 Approximately 13% of the new TB cases in 2013

were identified in patients infected with HIV, with the African region accounting for

78% of these cases.

9

In 2013, approximately 1.1 million deaths were reported among

HIV-negative cases and 0.36 million deaths were reported among HIV-positive

cases.

9 These deaths include 510,000 women and 80,000 children.

9

In the United States, 9,421 cases of TB were reported in 2014, and the incidence

rate was 2.96/100,000 population, which represents the lowest recorded rate since

national reporting began in 1953.

10 However, the incidence rate remained

substantially higher than the national goal for elimination of TB (<1 case per

1,000,000 population).

10 Twenty-one states reported increased numbers of TB cases

in 2014, and four states (California, Texas, New York, and Florida) accounted for

51% of all TB cases.

10 The number of TB cases and the incidence rates declined for

both foreign-born and US-born persons, but foreign-born and ethnic and racial

minorities continue to be disproportionally affected by TB in the United States. In

2014, 66% and 34% of all TB cases were reported in foreign-born and US-born

persons, respectively, and the TB rate was 13 times higher in foreign-born persons

compared with US-born persons (15.4 vs. 1.2 per 100,000 population).

10 Five

countries accounted for more than half of TB cases in foreign-born persons: Mexico

(21%), the Philippines (12%), India (8%), Vietnam (8%), and China (7%).

10 TB

rates for Hispanics, non-Hispanic blacks, and Asians were 8, 8.5, and 30 times

greater than the rate for non-Hispanic Caucasians.

10 Among US-born persons, the

greatest number of TB cases was reported in blacks. Among persons with TB whose

HIV status was known, 6% of these patients were coinfected with HIV.

10

In the United States, 9.3% of isolates from patients with no previous history of TB

were resistant to isoniazid in 2014; resistance was 7.5% in US-born individuals and

10.2% in foreign-born individuals.

10 Globally, there were approximately 480,000

cases of MDR-TB, defined as resistance to both isoniazid and rifampin, resulting in

210,000 deaths in 2013.

9 The largest number of MDR-TB cases were reported in

China, India, the Russian Federation, and South Africa.

9

In the United States, 67

cases of MDR-TB were reported in 2014.

10 The overall proportion of MDR-TB

cases in the United States has been stable over the last decade, ranging from 0.9% to

1.3%.

10 Foreign-born persons accounted for 85% of these MDR-TB cases.

10 The

percentage of MDR-TB is approximately 7 times higher for persons with a previous

history of TB compared with persons with no previous history of TB.

10 Several

conditions and risk factors for persons with increased risk of infection with drugresistant TB are shown in Table 68-1.

p. 1422

p. 1423

Table 68-1

Conditions and Risk Factors for Persons with Increased Risk of Drug-Resistant

Tuberculosis

History of treatment for latent tuberculosis infection or active disease

Patients from areas with high prevalence of initial or primary drug resistance (urban population, northeast United

States, Florida, California, Texas, United States–Mexico border)

Foreign-born persons from areas with high prevalence of drug-resistant tuberculosis (Southeast Asia, Mexico,

South America, Africa)

Contact with persons with active infection caused by drug-resistant Mycobacterium tuberculosis

Tuberculosis in persons who are homeless, abusers of intravenous drugs, and HIV infected

Patients with positive sputum smears and cultures after 2 months of treatment

HIV, human immunodeficiency virus.

In the mid-2000s, XDR-TB emerged as another major threat to global health.

4–6

The definition of XDR-TB is resistance to isoniazid and rifampin among first-line

agents, resistance to any fluoroquinolone, and resistance to at least one second-line

injectable drug (amikacin, kanamycin, or capreomycin).

11 According to the World

Health Organization, XDR-TB strains have been identified in 100 countries

worldwide, and an estimated 9% of patients with MDR-TB have XDR-TB.

9 One of

the first reports described 53 patients infected with XDR-TB from South Africa.

12

HIV status was known in 44 patients, and all of these patients were HIV positive.

Fifty-five percent of the patients had no prior history of TB treatment, and 98% died

with a median survival period of only 16 days after collection of the first sputum

specimen.

12