Hospital-Acquired Infections

Etiology

The risk for hospital-acquired infections depends on the facility's infection control practices, the patient's immune status, and the prevalence of the various pathogens within the community. The risk factors for HAI include immunosuppression, older age, length of stay in the hospital, multiple underlying comorbidities, frequent visits to healthcare facilities, mechanical ventilatory support, recent invasive procedures, indwelling devices, and stay in an intensive care unit (ICU).[5] Receipt of intravenous antibiotics within the last 90 days is 1 of the major risk factors for developing antimicrobial resistance to multiple drugs.[6] While hospitalizations play a major role in the management of acute illnesses, they also enhance the risk of susceptible patients to multiple nosocomial and often antimicrobial-resistant pathogens. These pathogens can be acquired from other patients, hospital staff, or the hospital facility. The risk is higher among patients in ICU. A point prevalence study that included 231,459 patients across 947 hospitals concluded that about 19.5% of patients in ICU had at least 1 HAI.[7]   

Clostridium difficile is the organism that causes Clostridium difficile colitis. Common organisms for CLABSI are candida spp (adult ICU), Enterobacteriaceae (adult wards, pediatric ICU and wards, and oncology wards), and staph aureus.[8] Common pathogens known to cause CAUTI are Enterococcus, staphylococcus aureus, Pseudomonas, Proteus, Klebsiella, and Candida.[9] According to the National Healthcare Safety Network, the common causative organisms for SSI include (in descending order) staph aureus, coagulase-negative staphylococcus, Enterococcus, E. coli, Pseudomonas aeruginosa, Enterobacter, Klebsiella pneumoniae.[10] The most common pathogens for HAP and VAP are staph aureus and Pseudomonas aeruginosa, while E. coli and Klebsiella pneumoniae can be seen in higher proportions among pediatric populations.[11]

Epidemiology

2014, the CDC published a multistate point prevalence survey of healthcare-associated infections involving 11,282 patients from 183 US hospitals.[12] According to this report, about 4% of hospitalized patients suffer from at least 1 of the HAIs. In absolute numbers, in 2011, an estimated 648,000 hospitalized patients suffered from 721,800 infections.[12] The dominant infections (in descending order) include Pneumonia (21.8%), surgical site infections (21.8%), gastrointestinal infections (17.1%), urinary tract infections or UTIs (12.9%), and primary bloodstream infections (9.9%, and include Catheter-associated bloodstream infections).[12] Among the pathogens causing HAI, C. difficile (12.1%) is the leading pathogen and is closely followed by Staphylococcus aureus (10.7%), Klebsiella (9.9%), and Escherichia coli (9.3%).[12] Skin and surgical site infections are usually caused by Staphylococcus aureus and sometimes include Methicillin-resistant staphylococcus aureus (MRSA). The SENIC study (Study on Efficacy of Nosocomial Infection Control) highlighted the possibility of reducing infections by a third by combining infection tracking and infection control programs.[13] Due to greater awareness and robust preventative measures undertaken in hospital settings, there has been some reduction in certain HAIs. Implementing robust infection surveillance and prevention practices has resulted in some success in preventing HAI. According to the CDC, the rates of CLABSI decreased by 46% between 2008 and 2013.[1]

Pathophysiology

Transmission of pathogens in a healthcare environment is complex and can occur through direct contact with healthcare workers or the surrounding contaminated environment. Risk factors for the development of Clostridium difficile infections are well known. These include recent antibiotic use, gastric acid suppressants, nonselective non-steroidal anti-inflammatory drugs (NSAIDs), and some comorbidities.[14] Risk factors for SSI include both patient factors such as age, diabetes, obesity, nutritional status, colonization, co-existing infections, and operative factors such as duration of the procedure, skin antisepsis, surgical technique, antimicrobial prophylaxis.[10] Some pathogens possess a tendency to colonize in areas with warmth and moisture. These areas are typically located in the inguinal and perineal region, axilla, and trunk. Certain bacteria and fungi thrive in such environments. 

Some of the proposed mechanisms of CAUTI are intraluminal colonization, retrograde intraluminal ascent, extraluminal peri urethral spread, and biofilms adherent to the urinary catheters.[15] Some organisms, such as Pseudomonas and Proteus species, can form tough biofilms around catheters. Sometimes, these pathogens produce enzymes that inactivate the antimicrobial agents, making it harder to treat these infections.[16] Mechanisms of infection in central line-associated bloodstream infections include colonization, biofilm formation, and extraluminal migration. The femoral site is associated with an increased risk of infections and should be avoided if possible.[17] Staphylococcus aureus and Staphylococcus epidermidis are common organisms associated with catheter biofilm formation.[18] Coagulase-negative staphylococci (CoNS), commonly found in skin flora, is a common cause of colonization of central lines and, thereby, central line-associated bloodstream infections. 

Multidrug-resistant (MDR) pathogens are also a significant cause of hospital infections, particularly in the intensive care unit. Infections with MDR organisms are associated with increased length of stay (LOS), mortality indicators, and care costs.[19] MDR pathogens are resistant to at least 1 antibiotic from 3 different classes or with different mechanisms of action.[20] MDR organisms are often suspected of HAP and VAP. The use of intravenous antibiotics within the past 90 days is an important risk factor for MDR infections.[3] Other risk factors for MDR VAP include the presence of septic shock at the time of VAP onset and duration of hospitalization, Acute respiratory distress syndrome, and acute renal replacement therapy before the onset of VAP.[3]

Toxicokinetics

Pharmacokinetics and pharmacodynamics change during an acute illness, especially during sepsis. For a given drug, the volume of distribution varies depending on the phase of the illness or recovery. This is an important concept and must be considered when determining dosing medication dosings, especially for drugs like aminoglycosides and beta-lactams. Another important determinant of the dosing of renal-excreted medications is the estimated glomerular filtration rate (eGFR), which may be impaired in sepsis. The IDSA and ATS recommend selecting antibiotic dosing based on pharmacokinetics and pharmacodynamics for critically ill patients with ventilator-associated Pneumonia.[21] An antibiotic's efficacy may be concentration-dependent (fluoroquinolones and aminoglycosides), time-dependent (beta-lactams), or a combination of both (Vancomycin). Time-dependent drugs are administered as extended infusions to maintain concentrations within 4 times the minimum inhibitory concentrations. In contrast, concentration-dependent drugs are dosed targeting 1 high peak (with a 1-time high dose) or multiple peaks with intermittent dosing.

History and Physical

Obtaining thorough details in history and a comprehensive physical examination is important in determining whether the infection was acquired before admission or is a hospital-acquired infection. Important pieces of history, such as subjective fever, chills, and night sweats, may indicate that the infection was not hospital-acquired. Common infectious symptoms include fever, chills, altered mental status, productive cough, shortness of breath, palpitations, abdominal pain, flank pain, suprapubic pain, polyuria, dysuria, and diarrhea. Vital signs can reflect signs of systemic inflammatory response or sepsis. These include hypothermia or hyperthermia, tachypnea, tachycardia, and hypotension. Examination of external devices such as tracheostomies, endotracheal tubes, foley catheters, intravascular lines, insulin pumps, and pacemakers/ defibrillators is essential. Supplementing the examination of external devices is the information on the location and placement of the device (duration and setting).

Central lines placed hastily during emergencies need to be re-evaluated and possibly replaced within 24 to 48 hours, especially in the context of aseptic conditions during line placement or a new fever during hospitalization. Central venous catheters are considered the primary source of hospital-acquired bloodstream infections. The other sources of bloodstream infections are catheter-associated urinary tract infections and ventilator-associated Pneumonia. The surgical sites and breaches in skin integrity should be examined daily for any signs of evolving infection. Thorough and serial examinations go a long way in identifying brewing infections in early phases, containing the infections, and minimizing complications. Careful examination of the abdomen and stool samples is often needed to evaluate clostridium difficile infection.

Evaluation

Laboratory testing complements the history and clinical examination in elucidating the possible source of infection and revealing evidence of organ dysfunction. Serum levels of lactic acid, liver transaminases, prothrombin time, blood urea nitrogen (BUN), and serum creatinine can support clinical findings of hypoperfusion. Other important lab findings include low or elevated white cell counts, elevated bands, thrombocytopenia, hypoglycemia, hyperglycemia, and reduced mixed venous blood saturation. Obtaining samples for cultures before the initiation of antibiotics is vital in the early identification of the pathogen and the antimicrobial susceptibility pattern. Pathogen and antibiotic susceptibility help narrow the range from broad-spectrum antibiotics to specific agents targeted toward the pathogens. Investigations that do not alter clinical decision-making or the clinical course are not usually recommended. Suppose the pretest probability is high for an HAI such as ventilator-associated pneumonia/ VAP. In that case, tests such as C-reactive protein (CRP) and procalcitonin are considered ancillary and not indicated. For patients with HAP/ VAP, recent IDSA guidelines recommend noninvasive sampling with tracheal aspirates as they have been shown to have non-inferior yield compared to invasive samplings such as quantitative tracheal lavage or bronchoscopy.[21] 

Treatment / Management

Management of hospital-acquired infections follows standard goal-directed therapy of sepsis, antibiotics, fluid resuscitation, and close monitoring for organ dysfunction. Serial assessments of the clinical and hemodynamic responses should follow fluid resuscitation. The selection and timing of initiation of antibiotics are critical. Empiric antibiotics should be selected based on risk factors for MDR pathogens and the patient's clinical stability. Antibiotics should be started early, within an hour if possible. If central line-associated bloodstream infection is suspected, two sets of blood cultures, 1 from a peripheral venous site and the other from the central venous catheter site, should be obtained before initiating antibiotic therapy. In case of hypotension, hypoperfusion, or organ dysfunction, the catheter must be removed without delay, and the tip should be sent for culture.

When suspecting catheter-associated urinary tract infections, the old catheter must be removed, and a urine sample from the newly placed catheter must be obtained, preferably before initiating antibiotics. These measures have been shown to enhance the yield of microbiological specimens. As part of the standard precautions, all catheters (including central lines and urinary catheters) should be removed if they are no longer indicated.[9] For catheter-associated UTIs, 7 days of antibiotics are typically recommended. However, in case of a delayed response or bacteremia, the antibiotic course could be extended to 10 - 14 days. Reducing usage, minimizing dwelling, using antimicrobial catheters, and using antibiotic prophylaxis in certain situations help prevent CAUTI.[9] The usual duration of the antibiotic regimen in HAP or VAP is 7 days unless a longer duration is clinically indicated.[21] Antibiotic regimens typically include activity against staph aureus and Pseudomonas aeruginosa.[3] MDR pathogens need different antibiotics than the usual antibiotics. (A1)

CLABSI incidence has decreased in the US over the years due to increasing awareness and implementation of evidence-based preventive strategies such as aseptic precautions at the time of insertion, removal of unnecessary catheters, chlorhexidine baths, antimicrobial dressings, and catheter lock solutions.[22] The antibiotic duration for central line-associated bloodstream infections depends on whether the infection is complicated or uncomplicated and whether the catheter is retained or removed. Determinants of complicated central line-associated bloodstream infections include suppurative thrombophlebitis, osteomyelitis, endocarditis, persistent positive cultures after 72 hours, and active malignancy or immunosuppression.[23] For Clostridium difficile infections, oral vancomycin is usually the drug of choice, and sometimes, the underlying antibiotic regimen for primary infection might need to be altered. Metronidazole is an alternative medication. Newer medications include fidaxomicin.[24] Other options, such as teicoplanin, among other antibiotics, are being explored.[24] Fecal microbiota transplantation is reserved for severe refractory cases.(A1)

Proper hand hygiene and appropriate infection prevention strategies must be followed postoperatively caring for surgical sites. Also, antibiotic prophylaxis and skin decontamination are important factors in preventing SSI.[10] Antibiotics to cover common pathogens in case of surgical site infections need to be employed early and later adjusted per reports from cultures. Antibiotics to cover staphylococcus aureus and other organisms such as Pseudomonas are usually initiated, depending upon the clinical scenario. Sometimes, antibiotics with activity against MDR pathogens such as MRSA and carbapenemase-producing Enterobacteria must be considered.[10] Universal standard (infection control) measures, such as handwashing with soap and water or using alcohol-based disinfectant before and after each patient visit, are vital in reducing transmission rates of MDR pathogens. In a study, gloves and gowns did not prevent contamination and conclusively did not seem enough to prevent the spread of infections.[25]

Differential Diagnosis

Differential diagnosis for hospital-acquired infections include the following:

• Bacterial sepsis
• Clostridium Difficile Colitis
• Pseudomonas
• Acinetobacter
• Enterococcal infections
• MRSA
• Legionella
• Viral hepatitis
• HIV
• Tuberculosis

Complications

Complications of hospital-acquired infections include:

• Sepsis
• Meningitis
• Endocarditis
• Osteomyelitis
• Peritonitis
• ARDs