Nosocomial Infections

Etiology

The etiology of HAIs is multifactorial, involving interactions between pathogens, host susceptibility, and the healthcare environment. Common sources include endogenous flora, contaminated equipment, healthcare personnel, and invasive procedures. The United States (US) Centers for Disease Control and Prevention broadly categorizes the types of HAI as follows:

1. Central line-associated bloodstream infections 
2. Catheter-associated urinary tract infections 
3. Surgical site infections (SSI)
4. Ventilator-associated pneumonia 

Other types of HAI include non-ventilator-associated hospital-acquired pneumonia, gastrointestinal infections (including Clostridioides difficile), primary bloodstream infections not associated with central lines, and urinary tract infections unrelated to catheter use. HAIs may also be classified by the affected organ system, including infections of the ear, eye, nose and throat; lower respiratory tract infections (eg, bronchitis, tracheobronchitis, bronchiolitis, tracheitis, lung abscess or empyema without evidence of pneumonia); skin and soft tissue; cardiovascular system; bones and joints; central nervous systems; and reproductive tract.

A 2015 point-prevalence survey conducted in US acute care hospitals identified pneumonia as the most common HAI, followed by gastrointestinal infections, SSIs, other systemic infections, bloodstream infections, and urinary tract infections.[1] The marked a shift from 2011 data, where pneumonia and SSI accounted for 21.8% each, followed by gastrointestinal (17.1%), urinary tract (12.9%), and bloodstream infections (9.9%).[1][5] Notably, the 2015 survey also highlighted non-ventilator-associated hospital-acquired pneumonia as the most prevalent HAI in acute care, consistent with findings from European studies.[2][6]

Causative Organisms

HAIs are primarily caused by bacteria, followed by fungi and viruses. The prevalence of specific pathogens varies across healthcare settings, facilities, locations, and patient populations. Each microorganism has distinct characteristics predisposing it to certain infections in susceptible hosts.

Bacteria

Bacterial pathogens in HAI may arise from endogenous flora or exogenous sources. Opportunistic infections occur when defenses are compromised. Common gram-positive organisms include coagulase-negative Staphylococci, Staphylococcus aureus, Streptococcus species, and Enterococcus species (eg, E faecalis, E faecium). Among all reported HAI pathogens, C difficile is the most frequently identified, accounting for 15% of infections with a known pathogen.[1][5] Gram-negative pathogens include members of the Enterobacteriaceae family (eg, Klebsiella pneumoniae and Klebsiella oxytoca, Escherichia coli, Proteus mirabilis, and Enterobacter species), Pseudomonas aeruginosa, Burkholderia cepacia, and Acinetobacter baumanii. A baumanii is associated with high mortality in the intensive care setting due to its extensive multidrug resistance.[7][8][9]

Multidrug-resistant bacteria are commonly seen in HAI and are associated with significant mortality.[9] Results from a study found that approximately 20% of all reported pathogens show multidrug-resistant patterns.[10] Notorious pathogens include methicillin-resistant Staphylococcus aureus, Vancomycin-intermediate S aureus, and vancomycin-resistant S aureus, Enterobacteriaceae with extended-spectrum cephalosporin resistance consistent with extended-spectrum beta-lactamase production, vancomycin-resistant Enterococcus, carbapenem-resistant Enterobacteriaceae and Acinetobacter species, and multidrug-resistant P aeruginosa.

Fungi

Fungal pathogens are typically opportunistic, affecting immunocompromised individuals and those with indwelling devices such as central lines or urinary catheters. Candida species, such as C albicans, C parapsilosis, and C glabrata, are the most common fungal agents.[1] C auris, an emerging multidrug-resistant species, poses a significant global concern due to diagnostic challenges, high morbidity, and frequent treatment failures.[11] Collectively, Candida species rank as the fourth most common pathogen in HAIs.[12] Aspergillus fumigatus, acquired through airborne transmission, particularly during hospital construction, may also originate from infected patients as a primary source.[13][14]

Viruses

Viral pathogens account for only 1% to 5% of all HAIs.[15] Healthcare-acquired hepatitis B, hepatitis C, and HIV are primarily associated with unsafe needle practices, particularly in resource-limited settings. Globally, an estimated 5.4% of HIV infections are healthcare-associated.[16] Other reported viral pathogens include rhinovirus, cytomegalovirus, herpes simplex, rotavirus, and influenza.

Epidemiology

HAIs significantly contribute to global morbidity, mortality, and healthcare costs. Although the actual global burden of HAIs is unclear due to limited surveillance in many regions, data from the US and Europe provide consistent epidemiologic insights. Most available studies originate from these regions. 

In European hospitals, HAI prevalence varies by care setting: 4.4% in primary care hospitals, 7.1% in tertiary hospitals, 19.2% in intensive care units (ICUs), and 3.7% in long-term care facilities.[2] An estimated 8.9 million HAI episodes occur annually in acute care and long-term healthcare facilities in the European Union. The 1995 European Prevalence of Infection in Intensive Care (EPIC) study reported a 20.6% prevalence of intensive care unit (ICU)-acquired infection.[17]

A study's results showed the prevalence of HAI among patients hospitalized in the US was 3.2% in 2015, a decline from 4.0% in 2011.[1] Further, 36.4% of HAIs occurred in critical care units, 57.5% in general wards or nurseries, and 6.1% in step-down, specialty, or mixed-acuity units. Results from earlier studies found HAI rates to be highest among adults and pediatrics outside the ICU, followed by patients in the ICU, high-risk neonatal nurseries, and well-baby nurseries.[18] 

In 2015, 687,200 (estimated) HAIs occurred in US hospitals, affecting 633,300 patients, markedly lower than the 1.7 million infections estimated in 2002.[1][18] The endemic burden of HAIs is notably higher in developing countries. A pooled analysis reported a prevalence of 15.5%, with VAP and neonatal infections in ICUs accounting for most cases.[3] A systematic review in Southeast Asia found an overall HAI prevalence of 9.1%.[19]

Pathophysiology

The interaction between microbial exposure, impaired host defenses, and invasive medical interventions drives the pathophysiology of HAIs. Devices such as catheters or ventilators often bypass natural barriers, allowing pathogens to colonize and infect normally sterile sites. Depending on the host response and the organism involved, this can lead to localized or systemic infection.

Routes of Transmission

Pathogens causing HAIs are transmitted through various routes, with contact transmission being the most common. This includes direct or indirect contact transmission and is associated with organisms such as methicillin-resistant Staphylococcus aureus, extended-spectrum β-lactamase–producing gram-negative bacteria, vancomycin-resistant Enterococcus, Clostridioides difficile, and rotavirus. Droplet transmission occurs via large respiratory droplets (>5 microns) that travel short distances (<3 feet), as seen with the influenza virus, Bordetella pertussis, and Neisseria meningitidis. Airborne transmission involves smaller droplets (<5 microns) that can travel longer distances, facilitating the spread of pathogens such as Mycobacterium tuberculosis, varicella-zoster virus, measles virus, and SARS-CoV-2.[20]

Central line–associated bloodstream infections

Central line–associated bloodstream infections (CLABSI) occur in patients with a central venous catheter (CVC) and are considered the most preventable type of HAI. Please see StatPearls' companion resource, "Central-Line Related Bloodstream Infections," for more information. In the US, 55% of individuals in the ICU and 24% of non-ICU individuals have CVC.[21] Infection typically occurs from skin flora migrating along the catheter's external surface into the bloodstream. Other routes include contamination during catheter insertion or manipulation, and hematogenous seeding. Many bacterial and fungal pathogens associated with CLABSI and catheter-associated urinary tract infections produce biofilm, enhancing adherence and persistence on device surfaces.[22]

Results from a recent US study identified common pathogens as S aureus (23%), Candida species (13%), coagulase-negative Staphylococcus (12%), Enterococcus species (12%), Streptococcus species (12%), E coli (8%), and Bacteroides species (6%). However, some studies' results still report coagulase-negative Staphylococci as the most common organism.[1][12][1][23] Antimicrobial resistance among these pathogens remains a significant concern.[9]

CLABSI risk factors are divided into host- and catheter-related factors. Host factors include immunosuppression (eg, chronic illness, neutropenia, malnutrition), parenteral nutrition, age extremes, and bone marrow transplantations. Catheter-related risks include prolonged hospitalization before catheterization, extended catheter dwell time, use of multilumen catheters, catheter material, multiple catheter placements, urgent insertions, and breaches in sterile barriers or aseptic technique. The association between femoral catheterization and an increased risk of CLABSI remains a topic of debate compared to subclavian or jugular sites.[23]

Catheter-associated urinary tract infections

Catheter-associated urinary tract infections (CAUTI) refer to urinary tract infections that occur in the presence of an indwelling urinary catheter placed for various medical indications. Please see StatPearls' companion resource, "Complicated Urinary Tract Infections," for more information. Approximately 15% to 25% of those hospitalized in the US receive a urinary catheter.

CAUTIs are classified as extraluminal or intraluminal. Extraluminal infections result from bacterial migration along the outer surface of the catheter from the urethral meatus to the bladder. Intraluminal infections arise from urinary stasis or ascending infection through a contaminated catheter lumen. Biofilm formation by bacterial or fungal pathogens facilitates colonization and persistence on catheter surfaces. Common pathogens originate from fecal and skin flora, with E coli being the most frequently reported, followed by K pneumoniae or oxytoca, Enterococcus species, P aeruginosa, and Candida species.[1][2][12] Complications of CAUTI include upper urinary tract involvement, sepsis, and bacteremia.

The primary risk factor for CAUTI is the duration of catheterization. Additional modifiable risks include breaches of the aseptic technique during insertion or maintenance. Patient-related risk factors include female sex, paraplegia, cerebrovascular disease, older age, diabetes mellitus, recent urinary tract infection, and antibiotic use within the prior 90 days.[24][25]

Surgical site infection

SSIs occur in 2% to 5% of patients undergoing surgery and usually manifest within 30 days postoperatively or within 90 days if an implant is involved.[26] SSIs are classified by depth and location: superficial (involving the skin and subcutaneous tissues), deep (involving muscle or fascia), and organ- or space-specific (involving the surgical field). Endogenous flora from the skin, gastrointestinal tract, or female genital tract may contaminate the surgical site, depending on the procedure.

Procedure-related risk factors include prolonged operative time (the most critical factor), wound classification, intraoperative hypothermia and hypovolemia, hypoxemia, emergency surgery, multiple procedures, need for blood transfusion, and type of prosthesis implanted.[27] Dirty, contaminated, and clean-contaminated wounds carry a significantly higher risk than clean wounds.[28] Postoperative factors, such as the use of wound drains, poor wound hygiene, and an extended postoperative length of stay, further increase the risk.[29]

Patient-related risk factors include immunosuppression, tobacco use, obesity, hyperglycemia, malnutrition, joint disease, and advanced age.[27][29] Common surgical site infection pathogens include Escherichia coli, Staphylococcus aureus, coagulase-negative Staphylococcus, Klebsiella, Enterobacter, Enterococcus, and Streptococcus species.[1][27] Exogenous sources, such as contaminated surgical instruments, the environment, or the actions of surgical staff, are less common and typically associated with clusters of infections.

Pneumonia

Hospital-acquired pneumonia (HAP) is defined as pneumonia occurring after 48 hours of admission, while ventilator-associated pneumonia (VAP) develops more than 48 hours after endotracheal intubation. Please see StatPearls' companion resource, "Nosocomial Pneumonia," for more information. VAP affects approximately 5% to 15% of mechanically ventilated individuals.[30] HAP and VAP may result from aspiration, inhalation of contaminated aerosols, bacterial translocation, or hematogenous spread. Common pathogens include S aureus, P aeruginosa, Candida species, K oxytoca and pneumoniae, Streptococcus species, and Enterobacter species.

Multidrug-resistant organisms are commonly seen in VAP. Host susceptibility depends on local factors, such as underlying lung disease, and systemic factors, including immunosuppression, neutropenia, age older than 70, dysphagia, or recent abdominal or thoracic surgery.[31] Risk factors for VAP include mechanical ventilation, sedation, supine positioning, inadequate oral care, physical deconditioning, and reintubation.[30][32] Risk factors for developing HAP or VAP with multidrug-resistant organisms include prior intravenous antibiotic use within the last 90 days, the need for mechanical ventilation, septic shock at the onset of VAP, preceding acute respiratory distress syndrome, hospitalization lasting more than 5 days before VAP onset, and the requirement for acute renal replacement therapy.[33]

Clostridioides difficile infection

C difficile is the single most commonly identified pathogen in HAIs.[1][5] Please see StatPearls' companion resource, "Clostridioides difficile infection," for more information. C difficile typically presents as antibiotic-associated diarrhea and colitis. Transmission occurs via the fecal-oral route and through aerosolized spores, leading to intestinal colonization.[34] The most critical risk factors for C difficile infections are antibiotic exposure and environmental contamination, both modifiable. Additional risk factors include advanced age, hospitalization, multiple comorbidities, use of gastric acid-suppressing medications, and immunosuppression.[35]

History and Physical

Clinical manifestations vary depending on the type of HAI, the causative pathogen, and the severity of illness. Presentations may range from localized symptoms, such as wound erythema or urinary urgency, to systemic signs like fever, hypotension, and sepsis. CLABSI typically presents with fever and rigors due to bacteremia in a patient with a central venous catheter in place or within 48 hours of its removal. Local signs such as insertion site erythema, purulence, or catheter dysfunction may be present but are not required for diagnosis and should not lower clinical suspicion. In some cases, CLABSI may first manifest as a complication of a bloodstream infection, including endocarditis, suppurative thrombophlebitis, septic arthritis, osteomyelitis, or deep abscess. 

Signs and symptoms of CAUTI mirror those of other urinary tract infections but occur in the presence of an indwelling urethral or suprapubic catheter, intermittent catheterization, or within 48 hours of catheter removal. Common signs and symptoms include fever, suprapubic or costovertebral angle tenderness, acute hematuria, catheter obstruction, dysuria, and urgency. The clinical presentation of SSI varies depending on the site of infection, its depth, and the causative pathogen. SSI typically develops within 30 days postoperatively or 90 days if prosthetic material is involved. Common signs include erythema, warmth, localized pain, and wound dehiscence. Purulent drainage, often seen in superficial incisional infections or from surgical drains, may also be present. Deep or organ/space infections are less apparent and tend to present with systemic features such as fever, rigors, significant pain, and leukocytosis.

Pneumonia typically presents with new-onset fever, cough, purulent sputum, and declining oxygenation. For a diagnosis of HAP or VAP, symptoms must begin more than 48 hours after hospital admission or mechanical ventilation, respectively. In sedated or intubated patients, signs may include fever, increasing oxygen requirement, and purulent secretions during endotracheal suctioning. On physical examination, findings may reveal coarse breath sounds and rales on auscultation. In the setting of parapneumonic effusions, breath sounds may be diminished.

Healthcare facility onset C difficile infection should be suspected in patients with 3 or more unformed stools within 24 hours after the third day of hospitalization, particularly in recent antibiotic use. Diarrhea is the hallmark symptom, but other manifestations may include abdominal pain, distention, cramping, fever, nausea, anorexia, and dehydration. For immunocompromised or older individuals who may not exhibit typical inflammatory responses, clinicians should maintain a high index of suspicion for C difficile infection when faced with nonspecific signs such as altered mental status, lethargy, fatigue, or changes in baseline vital signs, including tachycardia, hypotension, or respiratory compromise. 

Evaluation

Laboratory and diagnostic testing, in addition to clinical presentation and physical examination, are essential for confirming HAIs. Routine blood tests, such as complete blood counts, metabolic panel, inflammatory markers, and blood gases, can help assess for systemic infection. Specific diagnostic workups vary depending on the type of HAI. 

CLABSI

When CLABSI is suspected and no other source of infection is identified, blood cultures should be obtained before initiating antibiotic therapy. Samples should be drawn from two sites: central venous catheters and a peripheral vein. If purulent drainage is present at the catheter exit site, it should be cultured to determine the causative organism. 

CAUTI

If possible, urine samples should be collected from a midstream catch after catheter removal to minimize contamination from biofilm on the catheter. Urinalysis and urine cultures are essential for diagnosis. Pyuria is common in catheterized patients with bacteriuria. Asymptomatic bacteriuria, defined as culture growth of 100,000 colony-forming units (CFU)/mL of uropathogens in the absence of urinary tract infection symptoms, does not warrant treatment. A diagnosis of CAUTI is made when a patient exhibits clinical signs of infection that cannot be attributed to another source and a urine culture reveals greater than 1000 CFU/mL of 1 or more pathogens.

SSI

Evaluation of SSI should be guided by clinical presentation. When suspected, samples of infected tissue, drainage, or purulent material should be obtained for culture and susceptibility testing. Swabs may be used for deep wounds, but superficial swabs often yield polymicrobial colonization and may be less reliable. Imaging studies can aid in identifying organ or space infections and are particularly useful in guiding drainage of abscesses or fluid collections. 

HAP or VAP

Suspected HAP or VAP should be evaluated using imaging or microbiologic testing. A chest x-ray is the initial modality and may reveal more or progressive infiltrates. Laboratory findings may include leukocytosis or leukopenia. Respiratory samples should be obtained by noninvasive methods, such as endotracheal aspiration or expectorated sputum, or invasively through bronchoscopy with bronchoalveolar lavage or specimen brushing.[36] Samples should be stained, cultured, and tested for antimicrobial susceptibility. In select cases, specialized media may be required to isolate fastidious organisms such as M tuberculosis or fungal pathogens.

 C difficile Infection

Suspected C difficile infections (CDI) should be evaluated using stool tests for C difficile toxins or C difficile toxin genes. Only liquid stool from patients with clinically significant diarrhea should be tested to reduce false positives from highly sensitive assays. A rectal swab may be used for diagnostic purposes in patients with ileus. While nucleic acid amplification testing (NAAT) is highly sensitive, it carries a risk of overdiagnosis and overtreatment.[37]

An algorithmic approach is recommended, starting with enzyme immunoassays for toxins A and B and the glutamate dehydrogenase antigen. Indeterminate results should be confirmed with NAAT.[38] Colonoscopy is not routinely used for diagnosis, but pseudomembranous colitis, if observed, strongly suggests CDI. Imaging may be necessary in severe cases to evaluate for toxic megacolon or perforation.

Treatment / Management

The treatment and management of nosocomial infections require a multifaceted approach that includes prompt identification of the causative pathogen, targeted antimicrobial therapy, and removal or management of implicated medical devices. Additionally, adherence to infection control protocols and antimicrobial stewardship is crucial for reducing the transmission of infections and preventing the development of antimicrobial resistance. Management strategies vary depending on the type of infection, severity, and host factors. 

CLABSI

Based on the cultured organism and clinical context, central venous catheter (CVC) removal should be considered. Catheters infected with Candida species, S aureus, or P aeruginosa should be removed and replaced at an alternate site after blood cultures confirm clearance. Antimicrobial therapy and duration depend on the identified pathogen and severity of infection. Persistent bacteremia or the presence of high-risk organisms warrants further evaluation for metastatic complications.

Prevention remains the cornerstone of CLABSI management. Key measures include hand hygiene, skin disinfection with chlorhexidine, strict aseptic techniques, and ensuring that experienced operators perform CVC placement. Risk-reduction strategies involve daily assessment of CVC necessity, minimizing the number of catheters, and limiting lumens to those clinically required.[39]

CAUTI

Effective management of CAUTI requires both appropriate antimicrobial therapy and catheter management. Minimizing the use and duration of indwelling catheters is the most effective preventive strategy. Daily reassessment of catheter necessity is essential, and intermittent catheterization should be considered when feasible, as it is associated with lower infection rates.[40](A1)

In cases of CAUTI, catheter removal is recommended, particularly if the catheter has been in place for more than 2 weeks, due to biofilm formation and reduced treatment efficacy. Antimicrobial therapy should be guided by urine culture and susceptibility results, with empiric treatment informed by local antibiograms. Antiseptic-coated catheters, antimicrobial irrigation, or treated collection bags remain controversial and may contribute to the development of increased antimicrobial resistance.[40](A1)

SSI

Management of SSI involves prompt debridement of devitalized tissue and drainage of any purulent collections or abscesses. Empiric antimicrobial therapy should initially target the most likely pathogens based on the surgical site, with subsequent narrowing guided by culture results and clinical response, especially in polymicrobial infections where culture may not detect all organisms. Prevention of SSI includes pre-, intra-, and postoperative measures. Preoperative strategies focus on optimizing modifiable risk factors, appropriate antibiotic prophylaxis, and decolonization when indicated. Routine hair removal is discouraged due to the risk of microtrauma; hair should be clipped rather than shaved if necessary. Intraoperative measures include maintaining normothermia (>35.5 °C), euvolemia, adequate oxygenation, and blood glucose control (target <180 mg/dL), with re-dosing of antibiotics as needed for prolonged procedures. Postoperative measures include careful wound hygiene, monitoring of dressings and drains, and, in select cases such as those with dirty wounds or immunocompromised patients, short-term postoperative antibiotic prophylaxis.[41](A1)

HAP and VAP

The results of respiratory culture should guide antimicrobial therapy for HAP and VAP. If cultures cannot be obtained, empiric treatment should be initiated based on institutional guidelines and local antibiograms.[36] Empiric treatment for VAP typically includes coverage for P aeruginosa, MRSA, and other gram-negative bacilli. Dual anti-pseudomonal therapy may be warranted, depending on the patient's risk factors and resistance patterns.(B3)

In cases of suspected aspiration pneumonia, empiric coverage for oral anaerobes should be included. Antibiotic regimens should be de-escalated based on culture results and the patient's clinical stability. A lack of clinical improvement within 72 hours or rapid deterioration despite appropriate therapy should prompt an evaluation for complications or alternative sources of infection. VAP prevention strategies include minimizing mechanical ventilation duration, using light sedation protocols, promoting early mobilization, and conducting daily assessments of extubation readiness.[36](B3)

CDI

Hospital-acquired CDI is managed similarly to community-acquired cases. When possible, the inciting antibiotic should be discontinued. First-line treatments include oral vancomycin, fidaxomicin, and metronidazole in select cases. Recently approved fecal microbiota transplantation (FMT) products effectively treat recurrent CDI.[42][43] Management should follow the most current clinical guidelines, with therapy duration tailored to the disease severity, ongoing antibiotic use, and risk of recurrence. Surgical consultation and FMT may be indicated in severe or refractory disease cases.[44] Prevention of healthcare onset CDI relies on early identification, patient isolation, and strict contact precautions. Additional measures include proper hand hygiene, thorough environmental cleaning, and robust antimicrobial stewardship programs, particularly during outbreaks.(A1)

Differential Diagnosis

The differential diagnoses of HAIs depend on the presenting symptoms, type of infection, and individual risk factors. Differentiating HAIs from community-acquired infections is essential, as the causative pathogens and antimicrobial resistance patterns often differ significantly. Accurate classification ensures the appropriate treatment and implementation of infection control measures. A detailed review of symptom onset relative to healthcare exposure, such as recent hospitalization, use of broad-spectrum antibiotics, or central venous or urinary catheters, helps determine the likely source. Because many HAIs can mimic community-acquired infections, timing and clinical context are key to differentiation.

• CLABSI: In patients with bacteremia and no CVC, alternative sources of infection, such as wound infections, urinary tract infections (UTIs), pneumonia, or endocarditis, should be thoroughly investigated. When bacteremia develops in the presence of an indwelling CVC, other potential causes should be ruled out. Diagnosis of CLABSI requires careful evaluation of clinical presentation and symptom timing; symptoms should begin while the CVC is in place or within 48 hours of its removal. 
• CAUTI: Distinguishing CAUTI from community-acquired UTI is essential, as the latter occurs without recent urinary catheter use. UTIs may present as lower tract infections, such as acute cystitis or urethritis, or upper tract infections, including pyelonephritis, nephrolithiasis, or ureteritis. Accurate classification guides appropriate management and helps prevent unnecessary catheter-related interventions.  
• SSI: Postoperative fever may result from various causes unrelated to SSI, including atelectasis, pneumonia, UTI, medication adverse effects, or drug reactions. Other conditions may produce localized pain at the surgical site but are not classified as SSIs, such as wound dehiscence, wound herniation, cellulitis, burns, gas gangrene or myonecrosis, neoplasms, or septic thrombophlebitis. SSIs typically present within 30 days of surgery or up to 90 days in the presence of prosthetic material. Diagnosis requires clinical signs of infection in combination with diagnostic criteria, such as purulent drainage, positive cultures, or radiologic evidence, which vary by the type of SSI. 
• Pneumonia: As with other HAIs, the timing of respiratory symptom onset is key to distinguishing HAP from community-acquired pneumonia. The differential diagnosis for HAP is chronic obstructive pulmonary disease, asthma, pulmonary edema, bronchiectasis, pulmonary embolism, and upper respiratory tract infections. Differential diagnoses for VAP include acute respiratory distress syndrome, pneumonitis, pulmonary hemorrhage, pulmonary embolism, infiltrative malignancy, and drug-induced lung injury.
• Healthcare onset CDI: Diarrhea in those hospitalized should be carefully evaluated to distinguish healthcare onset CDI from other infectious or noninfectious causes. Noninfectious differentials include antibiotic-associated diarrhea unrelated to C difficile, inflammatory bowel disease, irritable bowel syndrome, malabsorptive diarrhea, and microscopic colitis. Infectious causes may involve viral, fungal, or bacterial pathogens. Antibiotic-associated organisms include S aureus, Salmonella, Bacteroides fragilis, Clostridium perfringens, or K oxytoca.[45] In severe cases, CDI-associated acute abdomen may mimic ileus, colonic pseudo-obstruction, ischemia, or volvulus.

Other Types of HAIs

Less common HAIs include soft tissue infections and those in the upper respiratory tract, the central nervous system, and the reproductive tract. Any infection with symptom onset following healthcare exposure may be considered an HAI. These often resemble their community-acquired counterparts, making clinical distinction essential.

Prognosis

The prognosis of HAIs depends on the infection type, illness severity, and the causative pathogen. Global morbidity and mortality remain poorly defined due to limited surveillance and analysis. However, results from numerous studies have provided estimates of HAI burden over time. The associated mortality, length of hospital stay, and healthcare costs are outlined below.

Mortality

Global mortality attributable to HAIs is not precisely known. However, study results report a 30-day mortality of approximately 10%, with crude mortality rates ranging from 12% to 80%, depending on patient population and definitions used.[46][47][48] Critically ill individuals appear to experience significantly higher excess mortality, even after adjusting for baseline severity.[17][49]

One international study reported ICU mortality rates of 25% in patients with HAI compared to 11% without, and overall mortality of 30% versus 15%, respectively.[8] The International Nosocomial Infection Control Consortium (2003–2008) reported excess mortality rates in ICUs of 29.3% for VAP, 23.6% for CLABSI, and 18.5% for CAUTI.[50] In 2002, HAIs in US hospitals were estimated to contribute 98,987 deaths, with the highest attributed to pneumonia (35,967), bloodstream infections (30,665), UTIs (13,088), SSIs (8205), and other sites (11,062).[18]

Length of Hospital Stay

The additional length of hospital stay due to HAIs varies by infection type and location of acquisition. Results from a German hospital study found an average increase of 12 days across all HAIS, with CAUTI, SSI, and primary bloodstream infections contributing 3.3, 12.9, and 12.5 additional days, respectively.[51] Patients with multiple HAIs experienced an extended length of stay of 25.6 days. In a US hospital, the length of stay was 26.30 days for patients with HAI compared to 5.69 days without.[52] In developing countries, HAIs have been associated with an additional length of stay ranging from 5 to 23 days.[19][53]

Associated Costs

In the US, the estimated annual cost of the 5 major HAIs in adult inpatients is $9.8 billion.[54] SSIs are the most costly (33.7%), followed by VAP (31.7%), CLABSI (18.9%), CDI (15.4%), and CAUTI (0.3%). The US Centers for Disease Control and Prevention estimates the total economic burden of HAIs to range from $28 billion to $45 billion annually. In Europe, HAIs are estimated to cost approximately €7 billion each year.[17]

Complications

Complications of HAIs vary widely based on the type of infection, severity of illness, and causative pathogen. While each HAI may result in a broad range of sequelae, the following outlines some of the more common complications associated with each primary type. 

• HAP and VAP
  • Respiratory failure
  • Empyema
  • Parapneumonic effusions
  • Sepsis
• CLABSI
  • Suppurative thrombophlebitis
  • Endocarditis
  • Septic arthritis
  • Osteomyelitis
  • Abscess
  • Sepsis
•  CAUTI
  • Upper urinary tract involvement
  • Sepsis
• SSI
  • Delayed wound healing
  • Rejection of implanted devices or prosthetics
  • Repeat surgery or removal of infected devices or prosthetics
  • Abscess formation
  • Body cavity infections
  • Sepsis
• Healthcare-onset CDI
  • Recurrent or difficult-to-treat infections
  • Ileus with toxic megacolon
  • Dehydration
  • Sepsis