Chapter 39: Community-Acquired Infections in the ICU

Community-acquired infections and concomitant sepsis are commonly a reason for admission to the ICU. In these infections, patients typically present with symptoms and signs prior to admission. The most common infections managed in the ICU are described below—CAP, UTIs, IAIs, necrotizing skin and soft tissue infections (NSTIs), and IE.

Introduction and Epidemiology

CAP is one of the most frequent causes of infection-related death in the United States. It occurs in approximately 4 million adults per year, accounting for 1.1 million hospitalizations and 50,000 deaths per year. Of the 20% to 60% of patients who require hospital admission for CAP, anywhere between 10% and 22% may require critical care.¹ Mortality rates remain high despite advances in antibiotics and critical care.

Pathogenesis

The lower respiratory tract remains sterile because of a combination of pulmonary defense mechanisms that involve anatomic and mechanical barriers, and humoral and cell-mediated immunity. The development of CAP is therefore a result of either a defect in the host pulmonary defense system, an exposure to a virulent or large inoculum of microorganisms, or a combination of these factors.² Certain risk factors for CAP have previously been described. These include increased age, male sex, malnutrition or poor dental hygiene, high alcohol consumption, smoking, immunosuppression including HIV, asplenia, and other underlying comorbidities.³

Microbiology

The most common etiology of CAP remains bacterial or viral; other fungal or parasitic organisms are isolated infrequently and are usually related to various geographic and host factors. Causes of bacterial CAP can be divided into typical or atypical organisms. The most common cause of CAP is Streptococcus pneumoniae; other typical bacterial pathogens include Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and gram-negative organisms such as Klebsiella pneumoniae and Pseudomonas aeruginosa, seen in patients with previous exposure to antimicrobials or structural lung disease. Community-associated methicillin-resistant S aureus (CA-MRSA) as an etiology of CAP should be considered in the appropriate clinical situation, usually in patients presenting with cavitary pneumonia, lung necrosis, or concurrent influenza.⁴ Atypical organisms, such as Mycoplasma pneumoniae, Chlamydophila spp. (Chlamydophila pneumoniae and Chlamydophila psittaci), and Legionella, can often result in admission to the ICU. Viral etiologies should not be overlooked and include influenza and respiratory syncytial virus; other viruses such as parainfluenza, human metapneumovirus, and adenovirus should also be considered. Influenza specifically should be included in the differential of anyone presenting with CAP in the typical season, especially given that a significant number of patients can have concomitant bacterial infection. Other pathogens in the appropriate host include Mycobacterium tuberculosis, specifically in patients who are homeless, recently incarcerated, have HIV, or are from a country where tuberculosis is considered prevalent. Endemic fungi such as Histoplasma capsulatum, Coccidioides immitis, and Blastocystis hominis should be considered in patients from the appropriate geographic region. Immunocompromised hosts, such as solid organ transplant recipients, hematopoietic stem cell transplant recipients, patients with HIV/AIDS, and patients on chemotherapy may be at risk for other opportunistic pathogens such as Aspergillus, Cryptococcus, and Pneumocystis jiroveci pneumonia.

Diagnosis

CAP is defined as acute infection of the lungs in patients who are not hospitalized or residents of long-term care facilities. Patients can present with symptoms of cough, fever, dyspnea, sputum production, and pleuritic chest pain. Other nonrespiratory symptoms may also be present. On physical examination, vital signs are notable for fever and associated tachycardia; hypotension is also present in severe CAP and concomitant septic shock. Tachypnea, the use of accessory muscles, or cyanosis and hypoxia are seen in respiratory compromise. Rales, bronchial breath sounds, and egophony are present on auscultation. On laboratory examination, leukocytosis with neutrophilic predominance is typically seen, although leukopenia can also occur in septic shock. Other signs of organ dysfunction such as acute kidney injury, hepatic dysfunction, lactic acidosis, and disseminated intravascular coagulation can also be seen with severe CAP and concomitant sepsis.

A chest radiograph should be performed and is critical to differentiating between upper respiratory and lower respiratory tract infection. Typically, a lobar infiltrate is present in bacterial pneumonia such as those seen in pneumococcal pneumonia; an interstitial pattern is typically seen with Mycoplasma and a bilateral mixed interstitial-alveolar pattern can be seen in viral pneumonia.² For patients hospitalized with suspected CAP but a negative chest x-ray, occasionally an infiltrate can be seen when the chest x-ray is repeated in 24 to 48 hours.⁵ Computed tomography (CT) of the chest is not routinely recommended given radiation exposure and expense; however, it may be useful in certain situations, such as nonresponse to initial therapy or in the immunocompromised host where certain infections such as Aspergillus and M tuberculosis have a classic appearance.²

In patients admitted to the ICU, certain diagnostic tests are recommended by Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) guidelines. All patients with severe CAP should have blood cultures done to guide antibiotic therapy. In addition, urinary antigens for Legionella pneumophila and S pneumoniae should be performed. These may be especially useful in pneumococcal pneumonia when initial antibiotics have been given and the utility of a positive blood culture may be reduced. In Legionella, culture is less sensitive and urinary antigen testing is a useful tool for diagnosis, although only positive in serogroup 1. In addition, rapid antigen or PCR testing for viruses such as influenza should be performed in the appropriate clinical setting. If expectorated sputum of good quality with minimal oropharyngeal contamination can be obtained, it should be sent for Gram stain and culture. In intubated patients with severe CAP, endotracheal aspirates or bronchoscopy can be done to obtain respiratory samples for culture, with significantly more yield.⁵

Management

Severity Scoring Systems

For each patient being evaluated for pneumonia, the following 2 questions need to be asked—“Should the patient be hospitalized?” and if so, “Should the patient be admitted to the ICU?” Several scoring systems have been developed to assess severity of illness in order to identify patients with severe CAP. The first 2 tools, the Pneumonia Severity Index (PSI) and CURB-65, can aid in the diagnostic decision of whether or not to admit someone to the hospital. The PSI, which has been validated in several large studies, uses age, comorbidity, and vital signs to determine if the patient can be discharged and treated as an outpatient. The second tool, the British Thoracic Society CURB-65 system, uses fewer variables—confusion, urea, respiratory rate, blood pressure (BP), and age, to determine if patients can be treated as an outpatient or should be admitted.⁶

In addition, the IDSA/ATS has developed criteria to aid in identifying patients that would require admission to the ICU (Table 39–1). Any patient with one of the major criteria, either vasopressor use or respiratory failure requiring intubation and mechanical ventilation, require admission to the ICU. Patients with 3 of the minor criteria should also be considered for direct admission to an ICU.

Validation studies support the use of the criteria in Table 39–1. Other scoring systems have been developed and include the SMART-COP, which aims to predict the need for respiratory or vasopressor support and the PIRO score, which aims to predict 28-day mortality.¹

Antimicrobial Therapy

The initial treatment for CAP is empiric therapy directed at the most common pathogens; specific risk factors based on the host as well as local hospital epidemiology should be taken into account when considering initial therapy. For patients admitted to the ICU with severe CAP, a beta-lactam for initial pneumococcal coverage and plus either azithromycin or a respiratory fluoroquinolone for atypical coverage is recommended. In patients with a severe penicillin allergy, a respiratory fluoroquinolone or aztreonam is recommended. If Pseudomonas is suspected based on risk factors such as structural lung disease in bronchiectasis or severe chronic obstructive pulmonary disease (COPD) with frequent steroid or antibiotic use, then an antipseudomonal beta-lactam is recommended (ie, cefepime, piperacillin-tazobactam or a carbapenem).

Drug-resistant pneumococcus has been reported, with about 85% of isolates susceptible to penicillin and up to 30% of isolates demonstrating resistance to macrolides.¹ Respiratory fluoroquinolone resistance remains low in North America. In cases where CA-MRSA is suspected, such as necrotizing pneumonia or lung abscess, linezolid or vancomycin should be added.⁵ In one randomized control trial for nosocomial pneumonia, linezolid has been shown to have clinical superiority to vancomycin although there was no difference in 60-day mortality.⁷ It is unclear if this data can be generalized to patients with CAP. Ceftaroline, which has activity against MRSA in addition to other gram-positive and gram-negative pathogens, was approved for the treatment of CAP based on phase III trials which demonstrated noninferiority to ceftriaxone for the treatment of non-ICU hospitalized CAP.⁸ Telavancin, a new gram-positive agent, which has activity against MRSA, has also been approved for hospital-acquired pneumonia.⁹ Daptomcyin is not effective in the treatment of MRSA pneumonia because it is inactivated by surfactant.

Antimicrobial therapy should be administered in the emergency department as quickly as possible in order to avoid delayed treatment, which has been associated with adverse outcomes. If a microbiological etiology is identified, treatment should be narrowed appropriately. In general, patients with CAP should be treated for at least 5 days,⁵ with the majority receiving around 7 to 10 days for severe CAP. Treatment can be continued with oral therapy once there has been clinical improvement. While studies on duration of therapy are generally limited, a randomized controlled trial looking at duration of therapy for ventilator-associated pneumonia (VAP) showed that 8 days of therapy were as effective as 15 days of therapy.¹⁰

Introduction and Epidemiology

UTI can be a challenging diagnosis and can present as various clinical syndromes ranging from acute uncomplicated UTI to acute pyelonephritis, complicated UTI, and prostatitis (Table 39–2). Severe infection and sepsis usually occur in patients with complicated UTI who have functional or structural abnormalities of the urinary tract.¹¹

The urinary tract is a common source of sepsis in critically ill patients, ranging from 9% to 30% in different cohorts.¹² Risk factors typically include obstruction or hydronephrosis, and mucosal trauma including presence of indwelling catheters or manipulation of the urogenital tract with surgery. Other studies have shown that older age, female gender, and other comorbidities such as liver cirrhosis and diabetes are risk factors for severe infection.¹¹

Pathogenesis

UTIs occur through 3 different mechanisms by which bacteria invade the urinary tract—ascending, hematogenous, lymphatic. The ascending route accounts for the majority of UTIs in women and involves bacterial pathogens that colonize the vagina and periurethral area that ascend to the bladder, for example after vaginal intercourse. The hematogenous route of infection involves seeding of the kidney in the setting of a bloodstream infection. The lymphatic route is uncommon and involves increased pressure in the bladder that directs lymphatic flow toward the kidney.¹³

Microbiology

The majority of UTIs are caused by Escherichia coli, isolated in 80% to 85% of episodes of community-acquired infections. In patients with complicated UTI who may have obstructive uropathy or neurogenic bladder, other Enterobacteriaceae such as Klebsiella or Enterobacter spp., Pseudomonas or Proteus are more likely to be isolated. Occasionally, gram-positive organisms such as Enterococcus or Staphylococcus as well as Candida spp. may be isolated, especially in patients with indwelling devices.¹¹ Renal abscesses have been described in patients with S aureus bacteremia and candidemia, presumably as a result of hematogenous infection. Antimicrobial resistance has been increasingly reported in community-acquired UTIs, specifically trimethoprim-sulfamethoxazole and fluoroquinolone resistance. The emergence of extended-spectrum beta-lactamase producing gram-negative organisms in community-acquired UTIs has also been described and renders limited treatment options.¹⁴

Diagnosis

The diagnosis of UTI can be challenging, especially in patients presenting with signs of sepsis. Patients should have symptoms of a UTI or history suggestive of a urinary source along with a positive urine culture. Symptoms of uncomplicated UTI include dysuria, urinary frequency, urgency, suprapubic pain, hematuria, or fever. Patients who present with symptoms of pyelonephritis may also have nausea, vomiting, flank pain, and concomitant bacteremia along with a positive urine culture. In addition, symptoms consistent with renal colic suggesting ureteral calculus or obstruction are also relevant in addition to history regarding recent urologic intervention, indwelling ureteral catheter, or presence of ureteral devices such as stents and nephrostomy tubes.¹¹

Physical examination should assess for costovertebral angle tenderness, hematuria, or presence of an indwelling device.¹¹ A clean catch urine sample should be sent for urinalysis and urine culture, and a positive urine culture is required for diagnosis of a urinary tract infection. Urine and blood cultures should be sent prior to administration of antimicrobial therapy, otherwise culture data may be falsely negative. If a patient has an indwelling urinary catheter in place, the urine sample should be sampled through the catheter port using aseptic technique or obtained from a freshly placed catheter, to avoid contamination of the urine sample. Typically, patients with a urinary source of infection have a single uropathogen isolated with greater than 10⁵ colony-forming units/mL. A blood culture isolate with similar susceptibilities as the urine culture typically confirms a urinary source of infection. Urinalysis with pyuria alone is not helpful in making the diagnosis of symptomatic UTI as often times pyuria, accompanies asymptomatic bacteriuria, is present after an urologic procedure or in the presence of a urinary catheter. Imaging of the kidneys and bladder is helpful to identify structural abnormalities that may require source control, such as a perinephric abscess or emphysematous pyelonephritis that may require drainage or obstruction that may require decompression.¹

Management

Antimicrobial therapy and source control should guide the management of critically ill patients with sepsis due to UTI. For pyelonephiritis requiring hospitalization, the IDSA guidelines recommend an intravenous fluoroquinolone with renal excretion such as levofloxacin or ciprofloxacin, an extended-spectrum cephalosporin (ceftriaxone, cefepime, ceftazidime), piperacillin-tazobactam, or a carbapenem.¹⁵ Local resistance data should be used to guide choice about initial therapy; for example, if fluoroquinolone resistance is known to be high, an extended-spectrum cephalosporin may be preferred. If there is a history of health care exposure or extended-spectrum beta-lactamase–producing organisms, then a carbapenem would be considered the drug of choice. Antibiotics should be administered rapidly, as this has previously been shown to improve outcomes in both severe UTI and sepsis.¹²

If a complicating factor in the urinary tract is identified, source control is warranted. In the management of an obstruction for example, decompression with percutaneous nephrostomy may be necessary; a large abscess may require drainage. In emphysematous pyelonephritis, initial percutaneous drainage is recommended with antimicrobial therapy, followed by nephrectomy if needed after the patient is stabilized.¹¹

Antibiotics should be narrowed based on urine culture and susceptibilities and can be transitioned to oral therapy once the patient has clinically improved. Traditionally, antibiotics for a 10- to 14-day course have been recommended for pyelonephritis and complicated UTI. However, recent data show that shorter courses of 7 days of treatment for acute pyelonephritis is equivalent to longer courses¹⁶ and the European Urology guidelines have recommended 3 to 5 days following defervescence and control of the complicating factor.¹¹ Treatment for acute bacterial prostatitis or abscess may require longer courses.

Introduction and Epidemiology

IAIs represent a diverse group of infections and are a common source of sepsis in patients hospitalized in the ICU. Mortality rates range from 30% to greater than 50% in patients with increased severity of illness at presentation and organ dysfunction.¹⁷

Pathogenesis

IAIs refer to the invasion of enteric bacteria into the wall of a hollow viscus. There are 2 types of IAI—uncomplicated or complicated. An uncomplicated IAI refers to an inflammatory process confined to the wall of an abdominal organ. It can often times be managed with surgical resection and perioperative antibiotic prophylaxis alone, that is, cholecystitis and appendicitis.¹⁸ A complicated IAI extends beyond the organ through a perforated viscus, into the peritoneal cavity. It is associated with peritonitis and/or the formation of an abscess.¹⁹

Microbiology

The microbiology of the gastrointestinal (GI) tract is complex and contains a wide variety of gram-positive, gram-negative, and anaerobic organisms. In the oral cavity, gram-positive cocci harbor the mouth and oropharynx, but in the distal small intestine gram-negative organisms begin to predominate. Bacterial colony counts increase further down in the GI tract, with the largest colony counts being in the colon, with a predominance of anaerobic organisms. Most IAI are therefore usually polymicrobial in nature. Often times, all organisms may not be identified in the laboratory, especially anaerobes. The most common organism isolated in patients with community-acquired intra-abdominal infections is E coli, followed by other Enterobacteriaceae, such as Klebsiella and Enterobacter. Typically gram-positive organisms, such as Enterococcus, are seen in patients with nosocomial infection or in patients who are immunocompromised or have previously received broad-spectrum antibiotics or cephalosporins.²⁰ Anaerobic organisms most frequently isolated include members of the Bacteroides family. Those patients who have a prolonged exposure to antimicrobial therapy often develop colonization and subsequent infection with other organisms such as Pseudomonas or Candida spp., and may develop infection with multidrug-resistant organisms such as multidrug-resistant Acinetobacter or vancomycin-resistant Enterococcus faecium.¹⁹

Clinical Presentation

The clinical presentation of IAI varies widely depending on location of the infection within the GI tract. In critically ill patients, the diagnosis can be especially difficult to make, given that history and physical examination may be limited in a sedated patient. Nonetheless, key history, physical examination, and laboratory and imaging findings together are essential to localizing intra-abdominal infection (Table 39–3).

Management

Management of IAIs is critical, especially in complicated IAI where morbidity and mortality are high in the ICU. Appropriate management involves both a combination of source control and appropriate antimicrobial therapy.

Source control refers to the concept of mechanical control of the source of infection, the elimination of ongoing contamination, and ultimately restoration of anatomy and function. In uncomplicated IAI, source control is sufficient to control infection and prevent development of complications, for example, an appendectomy. In complicated IAI, drainage or debridement along with a 5- to 7-day course of antimicrobials may be required. Drainage is used in the setting of an abscess and is commonly performed percutaneously using imaging. Surgical debridement is required in the setting of infected necrotic tissue.

Initial appropriate antimicrobial therapy is critical and has been shown to be associated with clinical outcome.²³ Empiric antimicrobial therapy should be directed against both aerobic and anaerobic gram-negative and gram-positive bacteria. Recommended empiric therapy includes a beta-lactam/beta-lactamase inhibitor such as piperacillin/tazobactam, a third- or fourth-generation cephalosporin with metronidazole, or a carbapenem.²⁴ Duration of therapy is 5 to 7 days if appropriate source control has been achieved.

Introduction and Epidemiology

NSTIs refer to the process of soft tissue necrosis secondary to toxin-secreting bacteria, and were first described by Hippocrates in 500 BC. During the Civil War, NSTI were further reported as “hospital gangrene” and noted to have high mortality rate. Since then, the pathogenesis of NSTI has been further described but is still associated with a high mortality rate anywhere from 25% to 35%.²⁵ Approximately 500 to 1500 cases have been described per year in the United States. Fournier gangrene is a variant of NSTI involving the penis, scrotum, or vulva. Risk factors such as diabetes mellitus, peripheral vascular disease, intravenous drug use, and other immunocompromising factors such as HIV and malignancy have been associated with NSTI.²⁵

Pathogenesis and Microbiology

NSTI is typically described as 2 types, type I and type II. Type I infections are monomicrobial and are caused by streptococci or clostridia species, and type II infections are polymicrobial. Other organisms associated with NSTI in specific clinical situations include Vibrio vulnificus, Aeromonas hydrophila, and MRSA. Necrosis of the fascial and muscle layers is caused by exotoxin production of these pathogens and results in a rapid progression of infection and cytokine production causing septic shock.²⁶

Diagnosis

The diagnosis of NSTI can be challenging; initial skin findings can vary from skin discoloration or cellulitis to gangrene or necrosis. Symptoms progress quickly and are usually associated with ecchymosis, blisters or bullae, edema, crepitus, or necrosis. Pain may be out of proportion to what is seen on physical examination, and there may be a hard, wooden feel to the subcutaneous tissues. Systemic findings include fever and signs of sepsis such as tachycardia and hypotension. Laboratory examination is significant for a leukocytosis with left shift, electrolyte disturbances such as acidosis and elevated creatine kinase. Radiologic findings include soft tissue stranding or edema in the deep fascial layers and the presence of gas is highly specific. Frozen section biopsy can also be done to confirm diagnosis of NSTI. If clinical suspicion is high for NSTI, early surgical evaluation is indicated.²⁵

Management

NSTI is considered a surgical emergency and requires aggressive resuscitation along with surgical debridement and broad-spectrum antibiotics. Surgical debridement of all necrotic tissue is paramount and should be done as early as possible in order to improve outcome. Antimicrobial therapy serves as an adjunct to source control and should cover gram-positive, gram-negative aerobic and anaerobic organisms. Initially, empiric coverage includes a broad-spectrum beta-lactam such as piperacillin-tazobactam or carbapenem along with empiric vancomycin. In streptococcal toxic shock syndrome or necrotizing fasciitis caused by group A streptococci, therapy should be penicillin along with clindamycin, which is added for suppression of streptococcal toxin and cytokine production. Antimicrobial therapy should be continued until operative treatment is no longer needed and there has been clinical improvement without fever for 42 to 78 hours.²⁷ Close monitoring in the ICU is important in order to provide supportive care with fluid resuscitation and optimal nutritional support.

Introduction and Epidemiology

IE remains relatively uncommon and affects about 10,000 to 15,000 people annually.²⁸ Men are affected more commonly and the median age of patients with IE is greater than 60. Common reasons for admission to the ICU include the development of congestive heart failure, septic shock, and neurologic deterioration.²⁹

Pathogenesis

The pathogenesis of IE involves initial damage to the endothelial surface of the valve, followed by platelet and fibrin deposition. This allows bacteria to subsequently adhere to the valve surface and produce disease at a lower inoculum.³⁰ Typical risk factors for IE include rheumatic heart disease, injection drug use, degenerative valve disease, prosthetic devices, and immunosuppression.²⁹

Microbiology

IE can be caused by several organisms, but is usually associated with S aureus and streptococci infection. S aureus is the most common cause of IE in the developed world, and is frequently associated with health care–associated infection. The streptococci make up a wide variety of organisms, but the viridans group streptococci are the most common pathogens associated with endocarditis, followed by Enterococcus and Streptococcus bovis. Coagulase-negative staphylococci, such as Staphylococcus lugdunensis have also increasingly been described. The HACEK organisms, Haemophilus spp., Aggregatibacter spp., Cardiobacterium spp., Eikenella corrodens, and Kingella, have been associated with culture-negative endocarditis, although sterile blood cultures in the setting of endocarditis can be due to several different factors.³⁰ Lastly, organisms other than bacteria, such as fungi, can also be a rare cause of endocarditis, the most common of which is Candida spp.²⁹

Diagnosis

The diagnosis of IE involves pathologic diagnosis on examination of the valve or the presence of major or minor criteria as described by the modified Duke criteria (Table 39–4). Blood cultures are critical to the diagnosis and 3 sets should be obtained in the first 24 hours. If the patient received antibiotics previously, more blood cultures may be required. Echocardiography is central to the diagnosis of IE, and transesophageal echocardiography (TEE) is more sensitive than transthoracic echocardiography (TTE). A good-quality TTE with a low clinical suspicion usually excludes the diagnosis of IE. However in cases where there is high clinical suspicion and TTE is negative or a suboptimal examination, TEE may be required. Occasionally repeat TEE after 7 to 10 days is needed to reassess for a vegetation in the setting of an initial negative examination.

Clinical Manifestations

Patients present with fever and other nonspecific symptoms, such as anorexia, weight loss, and malaise, especially in subacute cases. On examination, an audible heart murmur is heard about 85% of the time.³⁰ Other findings on physical examination include splinter hemorrhages (linear streaks in the fingernails or toenails), conjuctival petechiae, Osler nodes (small, painful nodular lesions on pads of fingers or toes), Janeway lesions (macular, painless plaques seen on palms or soles), and Roth spots (retinal lesions surrounded by hemorrhage).

The most common complication of IE is severe valvular regurgitation or heart failure. Major embolic phenomena are the second most common complication and may reflect the initial clinical presentation. Splenic emboli with infarction may cause left upper quadrant abdominal pain and renal infarction may present with hematuria. Renal abscess or glomerulonephritis may also be seen in the setting of IE. Mycotic aneurysms, or direct bacterial invasion or immune complex deposition in the arterial wall, can be seen in cerebral vessels or in the abdominal aorta. Neurologic complications are a common cause of initial ICU admission and include ischemic cerebrovascular accident (CVA), cerebral hemorrhage, or brain abscess. Right-sided IE may present as pulmonary embolism or infarction.³⁰ Anemia is almost always seen and erythrocyte sedimentation rate (ESR) is usually elevated, although laboratory parameters are not diagnostic.²⁹

Management

American Heart Association (AHA) and IDSA guidelines include recommended pathogen-guided antimicrobial therapy for IE, as listed in Table 39–5.³¹ Surgical indications in IE include heart failure not responsive to medical therapy, severe aortic or mitral regurgitation, endocarditis due to highly resistant organisms or persistent bacteremia, perivalvular infection with abscess, recurrent emboli or persistent vegetations, and large, mobile vegetations greater than 10 mm.²⁸