Nosocomial Infections

Etiology

Types of Healthcare-Associated Infection (HAI)

Responsible pathogens originate from a variety of different sources and are represented by different types of HAI. The Centers for Disease Control and Prevention broadly categorizes the types of HAI as follows:

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

Other types of HAI include non-ventilator-associated hospital-acquired pneumonia (NV-HAP), gastrointestinal infections (including Clostridioides difficile), other primary bloodstream infections—not associated with central catheter use, and other urinary tract infections—not associated with catheter use. HAI may also be grouped by affected systems such as ear, eye, nose and throat infections, lower respiratory tract infections (including bronchitis, tracheobronchitis, bronchiolitis, tracheitis, lung abscess or empyema without evidence of pneumonia), skin and soft-tissue infections, cardiovascular infection, bone and joint infections, central nervous systems infection, and reproductive tract infections.

A point-prevalence survey conducted in the United States in 2015 showed that the most common HAI in acute hospital settings is pneumonia, followed by gastrointestinal infections, SSI, other infections of the systems, as mentioned earlier, bloodstream infections, and urinary tract infections.[1] The prevalence of these types of infections has changed from point-prevalence surveys in 2011, which showed pneumonia (21.8%) and SSI (21.8%) as the most common, followed by gastrointestinal (17.1%), urinary tract (12.9%), bloodstream (9.9%) and other infections.[1][5] Interestingly, this same study showed that NV-HAP is the most common type of HAI in the acute health care setting, which is consistent with studies conducted in Europe.[2][6]

Causative Organisms

Pathogens responsible for nosocomial infections include bacteria, viruses, and fungi. Specific microorganisms have unique characteristics that favor particular types of infections in susceptible hosts. The prevalence of infections caused by particular microorganisms varies depending on the healthcare facility location, healthcare setting, and patient population. Overall, bacteria are the most common pathogens, followed by fungi and viruses.

Bacteria

Bacteria may originate from an exogenous or endogenous source as part of the natural flora. Opportunistic bacterial infections occur when there is a breakdown of the host immune system functions. Common Gram-positive organisms include coagulase-negative Staphylococci, Staphylococcus aureus, Streptococcus species, and Enterococcus species (e.g. faecalis, faecium). Of all HAI associated pathogens, C.difficile accounts for the most commonly reported pathogen in US hospitals (15% of all infections with a reported pathogen).[1][5] Common Gram-negative organisms include species of the Enterobacteriaceae family, including Klebsiella pneumoniae and Klebsiella oxytoca, Escherichia coli, Proteus mirabilis, and Enterobacter species; Pseudomonas aeruginosa, Acinetobacter baumanii, and Burkholderia cepacian. Acinetobacter baumanii is associated with high mortality within the intensive care setting owing to its inherent multi-drug resistant properties.[7][8][9]

Multidrug-resistant bacteria are commonly seen in HAI and are associated with significant mortality.[9] One study found that approximately 20% of all reported pathogens show multidrug-resistant patterns.[10] Notorious pathogens include methicillin-resistant Staphylococcus aureus (MRSA), Vancomycin-intermediate Staphylococcus aureus (VISA) and Vancomycin-resistant Staphylococcus aureus (VRSA), Enterobacteriaceae with extended-spectrum cephalosporin resistance consistent with extended-spectrum beta-lactamase (ESBL) production, vancomycin-resistant Enterococcus (VRE), carbapenem-resistant Enterobacteriaceae and Acinetobacter species, and multi-drug resistant Pseudomonas aeruginosa.

Fungi

Fungal pathogens are usually associated with opportunistic infections in immunocompromised patients and those with indwelling devices, such as central lines or urinary catheters. Candida species, such as C. albicans, C. parapsilosis, C.glabrata are the most commonly encountered fungal organisms associated with HAI.[1] Candida auris poses a serious problem as a globally emerging multidrug-resistant organism with high morbidity and mortality due to difficulty with diagnoses and high rates of treatment failure.[11] Altogether, Candida species make up the fourth most common pathogen across all types of HAIs.[12] Aspergillus fumigatus may be acquired by airborne environmental contamination in areas of healthcare construction. However, infected hospitalized patients may be a primary source.[13][14]

Viruses

Infections due to viral pathogens are the least reported, making up 1-5% of all HAIs pathogens.[15] Healthcare-acquired hepatitis B and C and human deficiency virus (HIV) has been implicated in unsafe needle practices. Globally 5.4% of all HIV infections are healthcare-associated and frequently occur in developing countries.[16] Other reported viral pathogens include rhinovirus, cytomegalovirus, herpes simplex virus, rotavirus, and influenza.

Epidemiology

Nosocomial infections affect a substantial number of patients globally, leading to increased mortality and financial impact on healthcare systems. While the actual global burden of healthcare-associated infection (HAI) remains unknown due to the lack of reliable data and surveillance systems, epidemiologic studies from Europe and the United States show relatively consistent results in surveillance programs. As such, most of the epidemiologic studies come from the United States and Europe.

Among European hospitals, the prevalence of at least one HAI varied based on the care setting: 4.4% in primary care hospitals; 7.1% in tertiary care hospitals; 19.2% in intensive care units; and 3.7% in long-term care facilities.[2] It is determined that approximately 8.9 million distinct HAI episodes occur annually in acute care and long-term health care facilities within the European Union. The 1995 European Prevalence of Infection in Intensive Care (EPIC) study showed a 20.6% prevalence of ICU-acquired infection.[17]

The prevalence of HAI among hospitalized patients in the US was 3.2% based on a survey in 2015, which was significantly lower than 4% in a study from 2011.[1] The same study showed that among HAI in US health facilities, 36.4% were attributed to critical care locations, 57.5% in ward or nursery locations, 6.1% in step-down or specialty care units, or mixed acuity locations (different levels of acute care).

An earlier study showed the area of HAI acquisition was highest among adults and children outside ICU, ICU patients, high-risk neonate nurseries, and then well-baby nurseries.[18] The estimated number of HAI in US hospitals in 2015 was 687,200, affecting 633,300 patients.[1] These figures are promising compared to those in 2002, which determined the annual number of HAI in US hospitals at 1.7 million.[18]

The endemic burden of HAI appears to be higher in developing countries. A pooled analysis of data from developing countries showed HAI prevalence of 15.5%, most of which occur as ventilator-associated pneumonia (VAP) and neonatal infections in intensive care settings.[3] A systemic review of HAI in Southeast Asian countries found the overall prevalence to be 9.1%.[19]

Pathophysiology

Routes of Transmission

Pathogens associated with healthcare-associated infection (HAI) may have different routes of transmission. The most common route of transmission is through contact, whereby the organisms are transmitted by direct or indirect contact. Common microorganisms that may be transmitted through contact are multidrug-resistant bacteria (such as MRSA, ESBL-producing Gram-negative organisms, VRE), C. difficile, and rotavirus. Droplet transmission may occur when microorganisms are transmitted from the respiratory tract by large droplets (greater than 5 microns) and travel less than 3 feet. Examples of infectious pathogens that are transmitted via the droplet route include influenza, Bordetella pertussis, and Neisseria meningitidis. Airborne transmission involves the transmission of organisms from the respiratory tract by small droplets (less than 5 microns) that travel long distances. Chickenpox virus, tuberculosis, measles, and the novel SARS-COV-2 virus may be transmitted through the airborne route.[20]

Central Line-Associated Blood Stream Infection (CLABSI)

CLABSI occurs in the setting of a central venous line (CVC) and is the most preventable type of HAI. In the United States, 55% of ICU patients and 24% of non-ICU patients have CVC.[21] CLABSI typically occurs when bacteria on the skin proliferate along the external portion of the catheter toward the intravascular part. Contamination of the CVC during insertion or manipulation process or by hematogenous seeding are other ways CLABSI can occur. Bacteria and fungal pathogens responsible for CLABSI and CAUTI frequently have virulence properties that result in biofilm production, which increases adherence and proliferation on external devices.[22] A recent study in the United States listed the common organisms associated with CLABSI as S. aureus (23%), Candida species (13%), coagulase-negative Staphylococcus (12%), Enterococcus species (12%), Streptococcus species (12%), E.coli (8%), Bacteroides species (6%). However, other studies still show coagulase-negative Staphylococci as the most common organism.[1][23][12] Among these pathogens, antimicrobial resistance is a serious problem.[9]

Risk factors for CLABSI may be divided into host and catheter factors. Host factors include immunocompromised statuses such as chronic illness, neutropenia, malnutrition, parenteral nutrition, extremes of ages, and bone marrow transplantations. Catheter factors include prolonged hospitalization before catheterization, prolonged time of catheterization, multi-lumen CVC, type of catheter material, multiple CVC, urgent insertion, and lack of sterile barriers or breaks in the aseptic technique. There exists some debate about whether femoral CVC carries an increased risk of CLABSI as compared to subclavian or jugular sites.[23]

Catheter-Associated Urinary tract Infection (CAUTI)

CAUTI is a urinary tract infection that occurs in the setting of an indwelling urinary catheter, which may be inserted for numerous medical indications. Approximately 15 to 25% of hospitalized patients in the United States have a urinary catheter. CAUTI can be classified as extraluminal or intraluminal. Extraluminal infections occur when bacteria track along the extraluminal surface of the catheter and enter from the urethral meatus to the bladder. Intraluminal infection arises when there is urinary stasis, usually due to blocked drainage or ascending infection from the intraluminal side of a contaminated catheter. Bacteria and fungal pathogens typically use biofilm formation to facilitate growth and spread along with the indwelling device.[24] Fecal and skin microflora generally are the culprit pathogens. Numerous studies have listed E.coli as the most common CAUTI pathogen, followed by Klebsiella pneumonia/oxytoca, Enterococcus species, Pseudomonas aeruginosa, and Candida species.[1][2][12] Complications of CAUTI include involvement of the upper urinary tract, sepsis, and bacteremia.

The most critical risk factor for CAUTI is the duration of catheterization. Operative or insertion protocol, such as nonadherence to aseptic techniques, is another modifiable risk factor. Patient characteristics that predispose to increased risk are female sex, paraplegia, cerebrovascular disease, older age, diabetes mellitus, history of UTI in the preceding year, and recent antibiotic use within 90 days.[25][26]

Skin and Soft Tissue Infection (SSI)

SSI occurs in 2-5% of patients undergoing surgery and usually manifest within 30 days of surgery or 90 days of implanted devices.[27] The infection depth and location determine the type of SSI: superficial SSI involves only the skin and subcutaneous tissues; deep SSI involves the muscle or facia, and organ or space-specific SSI occupy the anatomic vicinity of surgery. The patient’s skin, gastrointestinal tract, and female genital tract serve as a reservoir of the healthy flora that may contaminate the surgical site depending on the location of the surgery.

Procedure-related risk factors include the duration of surgery, wound class, hypothermia and hypovolemia during surgery, hypoxemia, the urgency of surgery, more than one intervention/surgery, necessity for blood transfusion, and the type of prosthesis implanted. The most critical risk factor is the duration of operation due to the time that the tissue is exposed to the environment leading to an increased chance of contamination.[28]

The wound class is also an important consideration, dirty, contaminated, and clean-contaminated wounds have the greatest risk compared to clean wounds.[29] Post-operative risk factors include the presence of wound drains, poor wound hygiene, and postoperative length of stay.[30] Patient-related risk factors include immunosuppression, tobacco use, obesity, hyperglycemia, malnutrition, joint disease, and increasing age.[28][30]

Common SSI pathogens are E.coli, S. aureus, Klebsiella species, Enterobacter species, Enterococcus species, Streptococcus species, Coagulase-negative Staphylococcus.[1][28][12] Exogenous sources of microorganisms from surgical instrumentation, environment, and operator are less common sources and usually occur in clusters of infections.

Pneumonia

Hospital-acquired pneumonia is pneumonia that develops after 48 hours of admission. Ventilator-associated pneumonia develops after 48 hours of endotracheal intubation. Approximately 5 to 15% of mechanically ventilated patients develop VAP.[31]

Patients develop HAP as a result of aspiration, inhalation of contaminated aerosols, bacterial translocation, and via hematogenous spread. Pathogens commonly associated with HAP and VAP include S. aureus, P. aeruginosa, Candida species, Klebsiella oxytoca and pneumoniae, Streptococcus species, and Enterobacter species. Multi-drug resistant organisms are commonly seen in VAP. Host susceptibility depends on local factors, such as underlying lung disease, or systemic factors, such as immunosuppression, neutropenia, age greater than 70, dysphagia, and recent abdominal or thoracic surgery.[32]

Mechanical ventilation, sedation, supine positioning, poor oral care, physical deconditioning, and reintubation are risk factors for VAP.[31][33] Risk factors for developing HAP or VAP with multi-drug resistant organisms are prior IV antibiotic use within the last 90 days, need for ventilatory support, septic shock at the time of VAP, acute respiratory distress syndrome preceding VAP, more than five days of hospitalization before VAP onset and need for acute renal replacement therapy.[34]

Clostridioides difficile Infection (CDI)

C. difficile is the single most common organism encountered in HAI.[1][5] CDI causes antibiotic-associated diarrhea and colitis. Colonization of the intestinal tract occurs by fecal-oral transmission and also through aerosolization of spores.[35] C. difficile produces toxins that act on intestinal epithelial cells leading to tissue injury and result in diarrhea. The most critical risk factor for healthcare-facility onset C. difficile infection (HO-CDI) is antibiotic use and environmental contamination, both of which are modifiable risk factors. Other frequently seen risk factors include increasing age, hospitalization, multiple comorbidities, use of gastric acid-suppressing medications, and immunosuppression.[36]

History and Physical

Clinical manifestations vary depending on the type of healthcare-associated infection (HAI), implicated pathogen, and the severity of illness.

Central Line-Associated Blood Stream Infection (CLABSI) will manifest with fever and rigors due to bacteremia in a patient having a central line at the time of infection or within 48 hours after removal. Purulence or erythema at the site of insertion and catheter dysfunction may occur, but absence should not minimize suspicion of CLABSI. Occasionally complicated infections due to the bloodstream infection (BSI) may be the first manifestation, such as endocarditis, suppurative thrombophlebitis, septic arthritis, osteomyelitis, or abscess.

Catheter-Associated Urinary Tract Infection (CAUTI)

Signs and symptoms of CAUTIare similar to other urinary tract infections, but they occur with indwelling urethral or suprapubic catheters, intermittent catheterization, or within 48 hours of removal of a catheter. Common signs and symptoms are fever, suprapubic or costovertebral angle tenderness, acute hematuria, catheter obstruction, dysuria, urgency.

Skin and Soft Tissue Infection (SSI) will have different clinical signs and symptoms based on the site, type of infection, and pathogen(s) involved. SSI usually occurs within the first 30 days post-operatively or 90 days in the setting of prosthetic devices. Signs of inflammation, such as erythema, warmth, and pain, and wound dehiscence, are seen in SSI. Purulent drainage may be present depending on the characteristics of the implicated organism and typically occurs in superficial incisional infections. Post-surgical drains may also drain purulent material. Deep tissue and organ-specific/space occupying infections are usually somewhat concealed and present with more systemic signs, such as fevers, rigors, more profound and extensive pain, and leukocytosis.

Pneumonia will manifest with new-onset fever, cough, purulent sputum production, and declining oxygenation. To meet the criteria for HAP or VAP, the symptoms should have an onset after 48 hours of hospitalization or ventilation, respectively. Sedated patients on mechanical ventilation may present with fevers, increasing oxygen requirement, and purulent material from endotracheal suctioning. Physical examination findings may reveal coarse breath sounds and rales on auscultation, in the setting of parapneumonic effusions, there may be decreased breath sounds.

Healthcare Facility Onset C. difficile Infection (HO-CDI) should be suspected in the setting of unexplained CDI symptoms, which include three or more unformed stools in 24 hours that occur within three days of hospitalization. Diarrhea is the cardinal symptom of CDI. However, other signs and symptoms may include abdominal pain, distention, cramping, fever, nausea, anorexia, and dehydration. Symptoms typically occur in the setting of recent antibiotic use.

It is vital to consider immunocompromised and elderly patients who may not mount robust immune responses to infection. In these special patient populations, a high index of suspicion for underlying infection should be kept when there are signs of altered mental status, lethargy, fatigue, and changes in baseline vitals (tachycardia, hypotension, respiratory status).

Evaluation

In addition to the clinical manifestations and physical examination, laboratory and other diagnostic testing are used to confirm diagnoses of healthcare-associated infection (HAI). Routine blood tests, which include complete blood counts, metabolic panels, inflammatory markers, and blood gases will be useful to evaluate for HAI. Each type of HAI will require different workup, as indicated below.

Central Line-Associated Blood Stream Infection (CLABSI)

With the clinical suspicion of CLABSI, in the absence of other localized infection(s), blood cultures should be drawn. Ideally, samples for blood cultures should be drawn from two different sites, for example, one from CVC and the other from a peripheral vein before starting antibiotic therapy. Any purulent material at the exit site should be cultured.

Catheter-Associated Urinary Tract Infection (CAUTI)

Urine samples should be collected from a midstream sample after removal of the urinary catheter, if possible. This prevents the chances of obtaining bacteria present in the biofilms present on the walls of the catheter. Urinalysis and urine cultures should be obtained. Pyuria is commonly seen in catheterized patients with bacteriuria. Bacteriuria, with culture growth of 100,000 colony forming units (CFU)/mL of uropathogenic bacteria without UTI symptoms, is referred to as asymptomatic bacteriuria and is typically not treated. In patients with clinical manifestations of CAUTI not explained by another source of infection, and urine culture growth greater than 1,000 CFU/mL of one or more pathogens are diagnosed with CAUTI.

Skin and Soft Tissue Infection (SSI)

The clinical presentation should guide the evaluation of SSI. When an SSI is suspected, a sample of the infected tissue, drainage, or purulent material should be cultured with an antibiogram. Swabs may be done on deep wounds. However, superficial swabs may be contaminated with polymicrobial colonization. Different modalities of imaging may be used to identify organ or space-occupying SSI, especially to guide drainage of infected fluid or abscess.

Hospital-Acquired Pneumonia (HAP)/Ventilator Associated Pneumonia (VAP)

A clinical diagnosis of pneumonia should be further evaluated with radiography and microbiologic findings. A chest x-ray is most commonly used and may reveal new infiltrates. Leukocytosis or leukopenia may be present. Sputum samples should be obtained by non-invasive sampling from endotracheal aspiration or expectoration or via bronchoscopy with bronchoalveolar lavage or specimen brushing.[37] Samples should be stained and cultured with antibiotic susceptibility testing. Depending on the clinical scenario, a specialized culture medium may be necessary to grow fastidious organisms, such as Mycobacterium tuberculosis or fungal pathogens.

C. difficile Infection (CDI)

Suspected CDI should be evaluated with stool tests for C. difficile toxin(s) or C. difficile toxin gene. Liquid stool from only clinically significant diarrhea should be sampled to limit false positives by highly sensitive diagnostic tests. A rectal swab may be done in patients with ileus and suspected CDI. Nucleic acid amplification testing (NAAT) is highly sensitive and may lead to overdiagnosis and overtreatment.[38]

An algorithmic approach with initial enzyme immunoassay for toxins A and B and glutamate dehydrogenase antigen is recommended. Indeterminate toxin or antigen tests should be confirmed with the use of NAAT.[39] Colonoscopy is not typically done for the sole purpose of diagnosing CDI. However, findings of pseudomembranous colitis are highly suggestive of CDI. Radiographic imaging may be warranted for patients with severe illness and suspected toxic megacolon or perforation.

Treatment / Management

Central Line-Associated Blood Stream Infection (CLABSI)

CVC catheter removal should be considered in specific circumstances and depending on the cultured organism. CVC infected with Candida, S. aureus, and Pseudomonas should be removed and replaced at an alternate site after subsequent blood cultures return negative. Antimicrobial therapy and duration are dictated by the specific organism that is cultured and severity of the infection. Further workup to evaluate for metastatic infections should be considered depending on the implicated organism and persistence of bacteremia after catheter removal. The second set of blood cultures should always be obtained to confirm clearance. Prevention of CLABSI is the best way to limit this type of HAI. Experienced operators should practice good hand hygiene, skin disinfection with chlorhexidine, and maintain aseptic techniques throughout the procedure. Interventions to mitigate the risk of CLABSI include daily review of CVC indication, minimizing the number of CVCs, and using only CVC with the required number of lumens.[40]

Catheter-Associated Urinary Tract Infection (CAUTI)

Both catheter management and anti-microbial therapy are needed to treat CAUTI. Minimizing the use and duration of indwelling catheters is the most important preventive step. Daily assessment of indications and the need for continued catheterization should be done. Intermittent catheterization is associated with lower rates of CAUTI and should be considered in patients who definitely need it.[24](A1)

In the setting of CAUTI, removal of the urinary catheter is recommended after two weeks of use due to biofilm formation and inadequate response to antimicrobial therapy. Antimicrobial therapy should be based on cultures and susceptibility testing. Providers should use hospital or community antibiograms to direct initial treatment. There is no clear consensus on the use of antiseptic-coated urinary catheters or collection bags or antimicrobial catheter irrigation; in fact, there is suspicion that this may lead to increased antimicrobial resistance.[24](A1)

Skin and Soft Tissue Infection (SSI)

SSI is treated by debridement of devitalized tissue and drainage of infected fluids, including abscesses. Anti-microbial therapy should initially be chosen with broad coverage for the most common pathogens associated with the specific site of infection. Narrowing anti-microbial coverage should be guided by the culture results and the patient’s clinical picture, as the cultures may not always capture all the implicated pathogens in polymicrobial infections. Preventive measures for developing SSI may be broken down into pre-operative, intra-operative, and post-operative. Pre-operative preventative measures include reducing host-modifiable risk factors, administering pre-operative antibiotics if indicated, and de-colonization of specific pathogens. Hair removal is not usually necessary, and shaving the area may cause microtrauma and introduce bacteria more deep-seated in the epithelium.[27] If hair removal is essential, hair should be clipped instead.

Intra-operative measures towards prevention include maintaining euthermia (temperature higher than 35.5 degrees Celsius), euvolemia, and avoiding hypoxemia, all of which are strategies to improve tissue oxygenation. Glycemic control should be achieved, keeping glucose concentrations less than 180mg/dL while avoiding hypoglycemia.  Intra-operative antibiotics may be re-dosed as needed depending on the duration of surgery. Post-operative measures involve maintaining hygiene to the area, monitoring dressings, incision sites, post-operative drains. Prophylactic postoperative antibiotics may be indicated in dirty or contaminated wound, where there is already a presumed infection, or in immunocompromised patients.[41](A1)

Pneumonia

The respiratory culture results should guide anti-microbial therapy for treating HAP and VAP. If a sample can not be obtained, empiric anti-microbial treatment should be started based on the hospital guidelines and hospital antibiograms for HAP and VAP. Patients should be reassessed daily for the need for continued anti-microbial therapy and depending on the level of suspicion of disease.[37] Empiric treatment for VAP consists of coverage for P. aeroginosa, MRSA, and other gram-negative bacilli. Dual anti-pseudomonal coverage may be necessary based on patient risk factors and the hospital antibiogram to treat VAP.(B3)

In the setting of suspected aspiration pneumonia coverage for oral anaerobes should be started. Antibiotics should be de-escalated based on culture results and clinical stability of the patient. If symptoms don't improve within 72 hours or the patient is rapidly deteriorating after appropriate treatment is started, further investigation into complications or alternate sources of infection should be considered. Steps to prevent VAP pneumonia include limiting exposure to mechanical ventilation, decreasing the duration on the ventilator, titrating to low levels of effective sedation, and early mobilization.[37](B3)

C. difficile Infection (CDI)

Hospital-acquired CDI is treated similarly to community-acquired CDI. If the infection is associated with antibiotic use, the initial step is to discontinue the inciting antibiotic if feasible. Oral vancomycin, oral fidaxomicin, and metronidazole are active against C. difficile. Providers should follow the most recent guidelines for the treatment and management of CDI. Duration of therapy depends on concomitant antibiotic use, the severity of illness, recurrent disease. Surgical evaluation and fecal microbiota transplantation may be warranted in severe disease.[42](B3)

Prevention HO-CDI requires close surveillance of clustered outbreaks in healthcare facilities. Prevention strategies are targeted toward early detection, prompt isolation, and implementation of contact precautions, proper hand hygiene, environmental cleaning and disinfection, and anti-microbial stewardship.

Differential Diagnosis

The differential diagnoses of healthcare-associated infection (HAI) depend on the presenting symptoms, type of infection, and risk factors for developing a specific kind of infection. Differentiating a community-acquired infection versus one that is attributed to healthcare acquisition is essential because associated pathogens and anti-microbial resistance patterns differ between HAI and non-HAI.

Having a correct distinction between HAI and community-acquired infections guides the clinician to treat and manage the patient appropriately. For this reason, a careful review of symptom onset is essential. Different types of infections develop after a specific exposure, for example, broad-spectrum antibiotic use, presence of a CVC, or urinary catheter. The timing of symptoms can tell us if the infection was present before or after the specific intervention or hospitalization. In this way, many types of HAI can mimic the community-acquired version of the infection.

Central Line-Associated Blood Stream Infection (CLABSI): Bacteremia in the absence of CVC should be investigated and search for any underlying source that can produce bacteremia. If bacteremia develops in the setting of indwelling CVC, other causes of infection should be ruled out. Bacteremia may arise from a variety of sources, for example, wound infection, urinary tract infection, pneumonia, and endocarditis. The clinical presentation and timing of symptoms onset should be carefully evaluated, and symptoms should have started in the presence of a CVC or within 48 hours after removal.

Catheter-Associated Urinary Tract Infection (CAUTI): It is crucial to differentiate CAUTI from community-acquired urinary tract infection, the latter of which occurs in the absence of urinary catheter use. Urinary tract infections may present as lower urinary tract infections, such as acute cystitis or urethritis, or upper urinary tract infections, pyelonephritis, nephrolithiasis, and ureteritis.

Skin and Soft Tissue Infection (SSI): Post-operative fever may occur in atelectasis with pneumonia, urinary tract infection, medication side-effect, or drug reaction. Other localizing conditions may produce pain at the surgical site but are not necessarily considered SSI, such as wound dehiscence, wound herniation, cellulitis, burns, gas gangrene or myonecrosis, tumor or neoplastic process, and septic thrombophlebitis. SSI typically develop within 30 to 90 days after surgery. The diagnosis of SSI requires both clinical features of infection plus diagnostic criteria, such as purulent drainage, positive cultures, or radiographic imaging. The criteria vary depending on the class of infection.

Pneumonia: As with other HAI, the timing of onset of respiratory symptoms should guide the clinician to diagnose community-acquired versus hospital-acquired pneumonia. HAP will have a symptom onset after 48 hours of hospitalization or ventilation. The differential diagnosis for HAP is COPD, asthma, pulmonary edema, bronchiectasis, and pulmonary emboli. Upper respiratory tract infections may also mimic pneumonia symptoms. Differential diagnoses for VAP include acute respiratory distress syndrome, pneumonitis, pulmonary hemorrhage, pulmonary embolism, infiltrative tumor, and drug reaction.

Hospital-Acquired C. difficile Infection (HO-CDI): Symptoms of diarrhea should be differentiated between other infections or noninfectious causes. Antibiotic-associated diarrhea not associated with C. difficile, inflammatory bowel disease, irritable bowel syndrome, malabsorptive diarrhea, microscopic colitis are differential diagnoses of noninfectious causes of diarrhea. Infectious diarrhea may be associated with viral, fungal, or bacterial pathogens. Antibiotic-associated diarrhea may also be due to S. aureus, Salmonella, Bacteroides fragilis, Clostridium perfringens, or Klebsiella oxytoca.[43] Acute abdomen associated with CDI can appear similar to ileus, colonic pseudo-obstruction, ischemia, or volvulus.

Other types of HAI outside of the five major groups of HAI, such as soft tissue, upper respiratory tract, central nervous system, and reproductive tract infections are less common but may occur. In general, any infection in which the symptoms begin after healthcare delivery may be attributed to HAI. The differential is broad and would mimic the community-acquired version of the infection.

Prognosis

The prognosis of healthcare-associated infection (HAI) varies on the type of HAI, the severity of illness, and the implicated pathogen. Worldwide morbidity and mortality are not well established due to limited surveillance and analysis. However, multiple studies over the years allow for estimates of the global burden of HAI. The mortality, length of stay, and associated costs associated with HAI are discussed below.

Mortality

The exact mortality attributed to HAI worldwide is not known, but some studies show 30-day mortality around 10% in patients who acquired HAI.[44][45] Others claim that the crude mortality rate associated with HAI varies from 12 to 80%, depending on the definition and populations under study.[46] Excess mortality due to HAI seems to be greater in critically ill patients, even after accounting for admission prognostic factors and severity scores.[17][47]

An international study showed that the ICU mortality rate of patients with HAI versus those without was 25% and 11%, respectively.[8] This same study also showed that the overall hospital mortality rate was again doubled in patients with HAI versus those without, 30%, and 15%, respectively. The International Nosocomial Infection Control Consortium 2003-2008 report from ICUs in Latin America, Africa, Asia, and Europe showed crude excess mortality in adult patients of 29.3%, 23.6%, and 18.5% in VAP, CLABSI, and CAUTI respectively.[48]

In 2002 the estimated deaths among US hospitals that were associated with HAI were 98,987 and varied by the type of infection: pneumonia (35,967), bloodstream infections (30,665), UTI (13,088), SSI (8,205), and other sites of infection (11,062).[18]

Length of Hospital Stay

Analysis of surveillance models in a German hospital showed that additional length of hospital stay (LOS) was sensitive to the location of acquisition and the type of HAI. The extra LOS due to all HAI was 12 days for all units but differed on the type of HAI such that CAUTI, SSI, and primary bloodstream infections were responsible for 3.3, 12.9, and 12.5 additional days, respectively.[49] Having multiple HAIs in the same patient prolonged extra LOS to 25.6 days. The LOS in patients with and without HAI was 26.30 and 5.69 days in a US hospital, respectively.[50] The additional LOS due to HAI in developing countries was reported between 5 to 23 days.[19][51]

Associated Costs

The annual costs of the five major types of HAI occurring in acute care hospitals are estimated to be $9.8 billion in US adult inpatient populations alone.[52] The most costly HAI are listed in the following order, along with the respective contributing percentages: SSI (33.7%), VAP (31.7%), CLABSI (18.9%), CDI (15.4%) and CAUTI (0.3%). The CDC estimates that all HAI cost the US healthcare system from $28 billion to $45 billion annually. In Europe, HAI-associated costs are approximately € 7 billion annually.[17]

Complications

Complications of healthcare-associated infection (HAI) are broad and depend on the type of infection, the severity of illness, and implicated pathogen. The list of complications of each type of HAI can be extensive, below a few of the more common complications of each HAI are listed.

Complications of Hospital Acquired Pneumonia (HAP)/Ventilator Associated Pneumonia (VAP)

• Respiratory failure
• Empyema
• Parapneumonic effusions
• Sepsis

Complications of Central Line-Associated Blood Stream Infection (CLABSI)

• Suppurative thrombophlebitis
• Endocarditis
• Septic arthritis
• Osteomyelitis
• Abscess
• Sepsis

Complications of Catheter-Associated Urinary Tract Infection (CAUTI)

• Upper urinary tract involvement
• Sepsis

Complications of Skin and Soft Tissue Infection (SSI)

• Delayed wound healing
• Rejection of implanted devices/prosthetics
• Repeat surgery or removal of infected devices/prosthetics
• Abscess formation
• Body cavity infections
• Sepsis

Complications of Hospital Acquired C. difficile Infection (HO-CDI)

• Recurrent or difficult to treat infections
• Ileus with toxic megacolon
• Dehydration
• Sepsis