Health Care-Associated Infections

ESSENTIALS OF DIAGNOSIS
Acquired during the course of receiving health care treatment for other conditions. Most cases are preventable. Hospital-associated infections are defined as not being present or incubating at the time of hospital admission and developing ≥ 48 hours after admission. Hand washing is the most effective prevention and should be done routinely even when gloves are worn.

General Considerations

Worldwide, approximately 10% of patients acquire a health care-associated infection, resulting in prolongation of the hospital stay, increase in cost of care, and significant morbidity and mortality. The most common infections are UTIs, usually associated with indwelling urinary catheters or urologic procedures; bloodstream infections, most commonly from indwelling catheters but also from secondary sites, such as surgical wounds, abscesses, pneumonia, the genitourinary tract, and the GI tract; pneumonia in intubated patients or those with altered levels of consciousness; surgical wound infections; MRSA infections; and Clostridioides difficile infection. There has been hospital-associated transmission of respiratory viruses, including SARS-CoV-2.

Some general principles are helpful in preventing, diagnosing, and treating health care-associated infections:

Many infections are a direct result of the use of invasive devices for monitoring or therapy, such as intravenous catheters, indwelling urinary catheters, shunts, surgical drains, catheters placed by interventional radiology for drainage, nasogastric tubes, and orotracheal or nasotracheal tubes for ventilatory support. Early removal of such devices reduces the possibility of infection.
Patients in whom health care-associated infections develop are often critically ill, have been hospitalized for extended periods, and have received several courses of broad-spectrum antibiotic therapy. As a result, health care-associated infections are often due to multidrug-resistant pathogens and differ from those encountered in community-acquired infections. For example, S aureus and S epidermidis (a frequent cause of prosthetic device infection) are often resistant to methicillin and most cephalosporins (ceftaroline is the only active cephalosporin against MRSA) and require vancomycin for therapy; Enterococcus faecium resistant to ampicillin and vancomycin; gram-negative infections caused by Pseudomonas, Citrobacter, Enterobacter, Acinetobacter, Stenotrophomonas, extended-spectrum beta-lactamases (ESBL)-producing E coli, Klebsiella, and carbapenem-resistant Enterobacteriaceae may be resistant to most antibacterials. When choosing antibiotics to treat the seriously ill patient with a health care-associated infection, antimicrobial history and the "local ecology" must be considered. In the most seriously ill patients, broad-spectrum coverage with vancomycin and a carbapenem with or without an aminoglycoside is recommended. Once a pathogen is isolated and susceptibilities are known, the most narrow-spectrum, least toxic, most cost-effective regimen should be used.

Widespread use of antimicrobial medications contributes to the selection of drug-resistant organisms; thus, every effort should be made to limit the spectrum of coverage and unnecessary duration. All too often, unreliable or uninterpretable specimens are obtained for culture that result in unnecessary use of antibiotics. The best example of this principle is the diagnosis of line-related or bloodstream infection in the febrile patient. To avoid unnecessary use of antibiotics, thoughtful consideration of culture results is mandatory. A positive wound culture without signs of inflammation or infection, a positive sputum culture without pulmonary infiltrates on CXR, or a positive urine culture in a catheterized patient without symptoms or signs of pyelonephritis are all likely to represent colonization, not infection.

Clinical Findings

A. Symptoms and Signs

Catheter-associated infections have a variable presentation, depending on the type of catheter used (peripheral or central venous catheters, nontunneled or tunneled). Local signs of infection may be present at the insertion site, with pain, erythema, and purulence. Fever is often absent in uncomplicated infections and, if present, may indicate more disseminated disease such as bacteremia, cellulitis and septic thrombophlebitis. Often signs of infection at the insertion site are absent.

1. Fever in an ICU Patient

Fever complicates up to 70% of patients in ICUs, and the etiology of the fever may be infectious or noninfectious. Common infectious causes include catheter-associated infections, hospital-acquired and ventilator-associated pneumonia (see Part 9), surgical site infections, UTIs, and sepsis. Clinically relevant sinusitis is relatively uncommon in the patient in the ICU.

An important noninfectious cause is thromboembolic disease. Fever in conjunction with refractory hypotension and shock may suggest sepsis; however, adrenal insufficiency, thyroid storm, and transfusion reaction may have a similar clinical presentation. Drug fever is difficult to diagnose and is usually a diagnosis of exclusion unless there are other signs of hypersensitivity, such as a typical maculopapular rash (most common with beta-lactams).

2. Fever in the Postoperative Patient

Postoperative fever is common and noninfectious fever resolves spontaneously. Timing of the onset of the fever in relation to the surgical procedure may be of diagnostic benefit.

A. IMMEDIATE FEVER (IN THE FIRST FEW HOURS AFTER SURGERY)- Immediate fever can be due to medications that were given perioperatively, to surgical trauma, or to infections that were present before surgery. Necrotizing fasciitis due to group A streptococci or mixed organisms may present in this period. Malignant hyperthermia is rare and presents 30 minutes to several hours following inhalational anesthesia and is characterized by extreme hyperthermia, muscle rigidity, rhabdomyolysis, electrolyte abnormalities, and hypotension. Aggressive cooling and dantrolene are the mainstays of therapy. Aspiration of acidic gastric contents during surgery can result in a chemical pneumonitis (Mendelson syndrome) that develops rapidly, is transient, and does not require antibiotics. Fever due to surgical trauma usually resolves in 2-3 days; however, it may be longer in more complicated operative cases and in patients with head trauma.

B. ACUTE FEVER (WITHIN 1 WEEK OF SURGERY)- Acute fever is usually due to common causes of hospital-associated infections, such as ventilator-associated pneumonia (including aspiration pneumonia in patients with decreased gag reflex) and line infections. Noninfectious causes include alcohol withdrawal, gout, PE, and pancreatitis. Atelectasis following surgery is commonly invoked as a cause of postoperative fever but there is no good evidence to support a causal association between the presence or degree of atelectasis and fever.

C. SUBACUTE FEVER (AT LEAST 1 WEEK AFTER SURGERY)- Surgical site infections commonly present at least 1 week after surgery. The type of surgery that was performed predicts specific infectious etiologies. Patients undergoing cardiothoracic surgery may be at higher risk for pneumonia and deep and superficial sternal wound infections. Meningitis without typical signs of meningismus may complicate neurosurgical procedures. Postoperative deep abdominal abscesses may require drainage.

B. Laboratory Findings

Blood cultures are universally recommended, and CXRs are frequently obtained. A properly prepared sputum Gram stain and semi-quantitative sputum cultures may be useful in selected patients where there is a high pretest probability of pneumonia but multiple exclusion criteria probably limit generalizability in most patients, such as immunocompromised patients and those with drug resistance. Other diagnostic strategies will be dictated by the clinical context (eg, transesophageal echocardiogram in a patient with S aureus bacteremia).

Any fever in a patient with a central venous catheter should prompt the collection of blood. The best method to evaluate bacteremia is to gather at least two peripherally obtained blood cultures. Blood cultures from unidentified sites, a single blood culture from any site, or a blood culture through an existing line will often be positive for coagulase-positive staphylococci, particularly S epidermidis, often resulting in the inappropriate use of vancomycin. Unless two separate venipuncture cultures are obtained-not through catheters-interpretation of results is impossible, and unnecessary therapy often results. Each "pseudobacteremia" increases bacterial resistance pressure, laboratory costs, antibiotic use, and length of stay. Microbiologic evaluation of the removed catheter can sometimes be helpful, but only in addition to (not instead of) blood cultures drawn from peripheral sites. The differential time to positivity measures the difference in time that cultures simultaneously drawn through a catheter and a peripheral site become positive. A positive test (at least 120 minutes' difference in time) supports a catheter-related bloodstream infection, while a negative test suggests catheters may be retained.

Complications

Complications such as septic thrombophlebitis, endocarditis, or metastatic foci of infection (particularly with S aureus) may be suspected in patients with persistent bacteremia and fever despite removal of the infected catheter. Additional studies such as venous Doppler studies, transesophageal echocardiogram, and CXRs may be indicated, and 4-6 weeks of antibiotics may be needed. In the case of septic thrombophlebitis, anticoagulation with heparin is also recommended if there are no contraindications.

Differential Diagnosis

Although most fevers are due to infections, about 25% of patients will have fever of noninfectious origin, including drug fever, nonspecific postoperative fevers (tissue damage or necrosis), hematoma, pancreatitis, PE, MI, and ischemic bowel disease.

Prevention

The concept of universal precautions emphasizes that all patients are treated as though they have a potential blood-borne transmissible disease, and thus all body secretions are handled with care to prevent spread of disease. Body substance isolation requires use of gloves whenever a health care worker anticipates contact with blood or other body secretions. Even though gloves are worn, health care workers should routinely wash their hands, since it is the easiest and most effective means of preventing hospital-associated infections. Application of a rapid drying, alcohol-based antiseptic is simple, takes less time than traditional hand washing with soap and water, is more effective at reducing hand colonization, and promotes compliance with hand decontamination. For prevention of transmission of C difficile infection, hand washing is more effective than alcohol-based antiseptics. Consequently, even after removing gloves, providers should always wash hands in cases of proven or suspected C difficile infection.

Peripheral intravenous lines should be replaced no more frequently than every 3-4 days. Some clinicians replace only when clinically indicated or if the line was put in emergently. Arterial lines and lines in the central venous circulation (including those placed peripherally) can be left in place indefinitely and are changed or removed when they are clinically suspected of being infected, when they are nonfunctional, or when they are no longer needed. Using sterile barrier precautions (including cap, mask, gown, gloves, and drape) is recommended while inserting central venous catheters. Antibiotic-impregnated (minocycline plus rifampin or chlorhexidine plus silver sulfadiazine) venous catheters reduce line infections. Silver alloy-impregnated indwelling urinary catheters reduce the incidence of catheter-associated bacteriuria, but not consistently catheter-associated UTIs. Best practices to prevent ventilator-associated pneumonia include avoiding intubation if possible, minimizing and daily interruption of sedation, pooling/draining of subglottic secretions above the tube cuff, and elevating the head of the bed. Silver-coated endotracheal tubes may reduce the incidence of ventilator-associated pneumonia but have limited impact on hospital stay duration or mortality, so they are not generally recommended. Catheter-related UTIs and intravenous catheter-associated infections are not Medicare-reimbursable conditions in the United States. Preoperative skin preparation with chlorhexidine and alcohol (versus povidone-iodine) reduces the incidence of infection following surgery. Another strategy that can prevent surgical site infections is the identification and treatment of S aureus nasal carriers with 2% mupirocin nasal ointment and chlorhexidine soap. Daily bathing of ICU patients with chlorhexidine-impregnated washcloths versus soap and water results in lower incidence of health care-associated infections and colonization. Selective decontamination of the digestive tract with nonabsorbable or parenteral antibiotics, or both, may prevent hospital-acquired pneumonia and decrease mortality but is in limited use because of the concern of the development of antibiotic resistance. Prevention bundles (implementing more than one intervention concomitantly) are commonly used as a practical strategy to enhance care.

Attentive nursing care (positioning to prevent pressure injuries, wound care, elevating the head during tube feedings to prevent aspiration) is critical in preventing hospital-associated infections. In addition, monitoring of high-risk areas by hospital epidemiologists is critical in the prevention of infection. Some guidelines advocate rapid screening (active surveillance cultures) for MRSA on admission to acute care facilities among certain subpopulations of patients (eg, those recently hospitalized, admission to the ICU, patients undergoing hemodialysis). However, outside the setting of an MRSA outbreak, it is not clear whether this strategy decreases the incidence of hospital-associated MRSA infections.

Vaccines, including hepatitis A, hepatitis B, and the varicella, pneumococcal, influenza, and SARS-CoV-2 vaccinations, are important adjuncts. (See section below titled Immunization Against Infectious Diseases.)

Treatment

A. Fever in an ICU Patient

Unless the patient has a central neurologic injury with elevated intracranial pressure or has a temperature higher than 41°C, there is less physiologic need to maintain euthermia. Empiric broad-spectrum antibiotics (see Table 32-1. Examples of Initial Antimicrobial Therapy for Acutely Ill, Hospitalized Adults Pending Identification of Causative Organism (Listed in Alphabetical Order by Suspected Clinical Diagnosis)) are recommended for neutropenic and other immunocompromised patients and in patients who are clinically unstable.

Table 32-1. Examples of initial antimicrobial therapy for acutely ill, hospitalized adults pending identification of causative organism (listed in alphabetical order by suspected clinical diagnosis).

Suspected Clinical Diagnosis	Likely Etiologic Diagnosis	Medication of Choice
Brain abscess	Staphylococcus aureus, gram-negative bacilli, streptococci, mixed anaerobes	Ceftriaxone, 2 g intravenously every 12 hours plus metronidazole, 500 mg orally/intravenous every 8 hours, plus vancomycin, 15-20 mg/kg intravenously every 8-12 hours¹
Endocarditis, acute	S aureus, Enterococcus faecalis, viridans streptococci	Vancomycin, 15-20 mg/kg/dose intravenously every 8-12 hours¹
Fever in neutropenic patient receiving cancer chemotherapy	S aureus, Pseudomonas, Klebsiella, Escherichia coli	Cefepime, 2 g intravenously every 8 hours. If concerned for MRSA infection, add vancomycin 15-20 mg/kg intravenously every 8-12 hours¹
Intra-abdominal sepsis (eg, postoperative, peritonitis, cholecystitis)	Gram-negative bacteria, anaerobic bacteria (ie, Bacteroides), enterococcus	Piperacillin-tazobactam, 4.5 g intravenously every 6-8 hours, or ertapenem, 1 g every 24 hours
Meningitis, bacterial, age >50 years, community-acquired	Streptococcus pneumoniae (pneumococcus), Neisseria meningitidis (meningococcus), Listeria monocytogenes,² gram-negative bacilli, group B streptococcus	Ampicillin, 2 g intravenously every 4 hours, plus ceftriaxone, 2 g intravenously every 12 hours, plus vancomycin, 15-20 mg/kg intravenously every 8-12 hours¹
Meningitis, bacterial, age 18-50 years, community-acquired	Pneumococcus,³ meningococcus	Ceftriaxone, 2 g intravenously every 12 hours,³ plus vancomycin, 15-20 mg/kg intravenously every 8-12 hours¹
Meningitis, postoperative (or posttraumatic)	S aureus, gram-negative bacilli, coagulase-negative staphylococci, diphtheroids (eg, Cutibacterium acnes)	Vancomycin, 15-20 mg/kg intravenously every 8-12 hours¹ , plus cefepime, 2 g intravenously every 8 hours
Osteomyelitis	S aureus, secondarily gram-negative aerobes	Vancomycin 15-20 mg/kg intravenously every 8-12 hours,¹ plus ceftriaxone 2 g intravenously every 24 hours
Pneumonia, community-acquired, non-ICU hospital admission	Pneumococci, Haemophilus influenzae, Mycoplasma pneumoniae, Legionella, Chlamydia pneumoniae	Ceftriaxone, 1 g intravenously every 24 hours or ampicillin-sulbactam 1.5-3 g intravenously every 6 hours) plus azithromycin, 500 mg intravenously every 24 hours; or a respiratory fluoroquinolone⁴ alone
Pneumonia, postoperative or nosocomial	S aureus, gram-negative bacilli	Cefepime, 2 g intravenously every 8 hours; or ceftazidime, 2 g intravenously every 8 hours; or piperacillin-tazobactam, 4.5 g intravenously every 6-8 hours; or imipenem, 500 mg intravenously every 6 hours; or meropenem, 1 g intravenously every 8 hours plus vancomycin, 15-20 mg/kg/dose intravenously every 8-12 hours¹ Empiric combination therapy for gram-negative bacilli may be considered based on local susceptibility patterns. Secondary agents include ciprofloxacin, 400 mg intravenously every 8 hours or tobramycin, 5-7 mg/kg intravenously every 24 hours
Pyelonephritis with flank pain and fever	E coli, Klebsiella, Proteus	Ceftriaxone, 1 g intravenously every 24 hours; or if culture results confirm susceptibility, ciprofloxacin, 400 mg intravenously every 12 hours (500 mg orally); or levofloxacin, 500 mg once daily (intravenously/orally)
Septic arthritis	S aureus, Neisseria gonorrhoeae	Ceftriaxone, 1-2 g intravenously every 24 hours plus vancomycin 15-20 mg/kg/dose intravenously every 8-12 hours¹
Septic thrombophlebitis	S aureus, gram-negative aerobic bacteria	Vancomycin, 15-20 mg/kg/dose intravenously every 8-12 hours¹ , plus ceftriaxone, 1 g intravenously every 24 hours

¹ Vancomycin serum levels should be monitored. Select drug interval based on estimated kidney function and dose rounded to nearest 250 mg.

² TMP-SMZ can be used to treat Listeria monocytogenes in patients allergic to penicillin in a dosage of 15-20 mg/kg/day of TMP in three or four divided doses. Dose reduction is necessary for patients with reduced kidney function.

³ Including penicillin-resistant isolates.

⁴ Levofloxacin 750 mg/day, moxifloxacin 400 mg/day.

B. Catheter-Associated Infections

Factors that inform treatment decisions include the type of catheter, the causative pathogen, the availability of alternate catheter access sites, the need for ongoing intravascular access, and the severity of disease.

In general, catheters should be removed if there is purulence at the exit site; if the organism is S aureus, gram-negative rods, or Candida species; if there is persistent bacteremia (more than 48 hours while receiving antibiotics); or if complications, such as septic thrombophlebitis, endocarditis, or other metastatic disease, exist. Central venous catheters may be exchanged over a guidewire provided there is no erythema or purulence at the exit site and the patient does not appear to be septic. Methicillin-resistant, coagulase-negative staphylococci are the most common pathogens; thus, empiric therapy with vancomycin, 15 mg/kg/dose intravenously twice daily, should be given assuming normal kidney function. Empiric gram-negative coverage should be used in patients who are immunocompromised or who are critically ill (see Table 32-1. Examples of Initial Antimicrobial Therapy for Acutely Ill, Hospitalized Adults Pending Identification of Causative Organism (Listed in Alphabetical Order by Suspected Clinical Diagnosis)).

Antibiotic treatment duration depends on the pathogen and the extent of disease. For uncomplicated bacteremia, 5-7 days of therapy is usually sufficient for coagulase-negative staphylococci, even if the original catheter is retained. Fourteen days of therapy are generally recommended for uncomplicated bacteremia caused by gram-negative rods, Candida species, and S aureus. Antibiotic lock therapy involves the instillation of supratherapeutic concentrations of antibiotics with heparin in the lumen of catheters. The purpose is to achieve adequate concentrations of antibiotics to kill microbes in the biofilm. Antibiotic lock therapy can be used for catheter-related bloodstream infections caused by both gram-positive and gram-negative bacterial pathogens and when the catheter is being retained in a salvage situation.

When to Refer

Any patient with multidrug-resistant infection.
Any patient with fungemia, S aureus bacteremia, or persistent bacteremia of any organism.
Patients whose catheters cannot be removed.
Patients with multisite infections.
Patients with impaired or fluctuating kidney function for assistance with dosing of antimicrobials.
Patients with refractory or recurrent C difficile infection.

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