Hospital-acquired infections also known as healthcare-associated infections are nosocomially acquired infections that are typically not present or incubating at the time of admission.They are monitored closely by agencies such as the Center for Disease Control and Prevention (CDC) in efforts to prevent their occurrence and improve patient safety. These infections include central line-associated bloodstream infections, catheter-associated urinary tract infections, surgical site infections, hospital-acquired pneumonia, ventilator-associated pneumonia, and Clostridium difficile infections.
Recently, the 2016 guidelines from the Infectious Disease Society of America and American Thoracic Society have changed the definitions of pneumonia to be better to identify patients at risk of multidrug-resistant (MDR) pathogens to avoid overuse of antibiotics. The previous term of healthcare-acquired pneumonia (HCAP) has been made obsolete. Hospital-acquired pneumonia is defined as pneumonia that occurs 48 hours or more after admission and did not appear to be incubating at the time of admission. Ventilator-associated pneumonia is defined as pneumonia that develops more than 48 to 72 hours after endotracheal intubation.
The risk of hospital-acquired infection is dependent on the patient's immune status, infection control practices, and the prevalence of the various pathogens in the local community. Risk factors for hospital-acquired infections include older age, immunosuppression, longer hospital stays, multiple underlying chronic illnesses, frequent encounters with healthcare facilities, recent invasive procedures, mechanical ventilatory support, indwelling devices and stay in a critical care unit with an increased risk of hospital-acquired infections. One of the major factors for developing antimicrobial resistance to multiple drugs is prior receipt of antibiotics within the last 90 days. While hospitalizations play a role in the management of acute illness, they also place susceptible patients in contact with multiple nosocomial and often antimicrobial-resistant pathogens and those from other patients, hospital staff, or the hospital facility. Not surprisingly, about 20% of all nosocomial infections occur in the intensive care unit (ICU).
A multistate point prevalence survey of healthcare-associated infections involving 11,282 patients from 183 US hospitals published by the CDC in 2014 had 4% of inpatients suffering from at least one of the healthcare-associated infections giving an estimated 648,000 inpatients suffering from 721,800 infections in 2011. Pneumonia (21.8%) and surgical site infections (21.8%) were the leading causes, followed by gastrointestinal infections (17.1%), urinary tract infection (12.9%) and primary bloodstream infection (9.9%). Among the pathogens causing hospital-acquired infections, C. difficile (12.1%) is the leading cause followed by Staphylococcus aureus (10.7%), Klebsiella (9.9%) and Escherichia coli (9.3%).
Due to greater awareness and preventative measures, there has been some progress in reduction in the incidence of some types of hospital-acquired infections. From 2008 through 2014, there was a 50% decrease in central line-associated bloodstream infections. There was a 17% decrease in surgical site infections related to specific procedures. From 2011 through 2014, there was an 8% decrease in C. difficile infections. There was a 13% decrease in methicillin-resistant S. aureus (MRSA) bacteremia between 2011 through 2014.
Transmission of pathogens can occur by direct contact with healthcare workers or contaminated environment. Pathogens tend to colonize in warm and moist areas such as inguinal and perineal area, axilla, and trunk. Some organisms can form tough biofilms around catheters such as Pseudomonas species, Acinetobacter baumannii, and Stenotrophomonas maltophilia. Extraluminal migration of organisms is the major route of infection in central line-associated bloodstream infections. This explains why coagulase-negative staphylococci, commonly found in skin flora is the most common cause of colonization of central lines and hence central line-associated bloodstream infections. Multidrug-resistant organisms (MDR) are also a significant cause of infections in the hospitals, particularly in the intensive car unit, with a propensity to increase the length of stay and mortality. MDR organisms are resistant to at least two antibiotics of different classes or mechanism of action, often suspected in the case of hospital-acquired pneumonia and ventilator-associated pneumonia. Universal standard precautions such hand washing with soap and water or alcohol-based disinfectant before and after seeing every patient are vital in reducing rates of transmission. In one study of a 20-bed neonatal unit, use of gloves alone did not prevent contamination.
Pharmacokinetics and pharmacodynamics change during acute illness, particularly during sepsis. The volume of distribution can increase or decrease depending on the phase of illness or recovery, and this must be considered when dosing medications such as aminoglycosides and beta-lactams. Estimated glomerular filtration rate (eGFR) may also be impaired early in sepsis potentially affecting dosing of renally eliminated medications, and in this regard, it is important to know that eGFR is impaired before the actual rise in serum creatinine. The Infectious Disease Society of America and American Thoracic Society recommend selecting antibiotic dosing based on pharmacokinetics and pharmacodynamics for critically ill patients with ventilator-associated pneumonia. 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 typically administered as extended infusions to maintain concentrations typically within four times of minimum inhibitory concentrations, whereas concentration-dependent drugs are dosed as a one-time high dose targeting high peaks or in an intermittent fashion with multiple peaks.
Clinical judgment is important in determining whether the patient had an infection before admission or whether they acquired it in the hospital. Constitutional symptoms before admission such as subjective fever, chills, night sweats may indicate that the patient's sepsis was not acquired in the hospital. Symptoms that favor an infection include altered mental status, productive cough, shortness of breath, palpitations, abdominal pain, rebound tenderness, suprapubic pain, polyuria, dysuria, costovertebral angle tenderness. On physical exam, vital signs can reflect signs of sepsis such as hyperthermia or hypothermia, hypotension, tachypnea, tachycardia and low oxygen saturation. Examination of the integrity of external devices such as tracheostomies, endotracheal tubes, intravascular lines, foley catheters, insulin pumps, pacemakers and defibrillators, and prosthetics is also important including the information on the location of the device, when it was placed, and where it was placed. A femoral central line placed hastily in the emergency room during a code blue would need to be re-evaluated in the context of a new fever during hospitalization, but if asepsis during placement will be in question, then replacement with a new central access elsewhere under sterile precautions must be done within 24 hours to 48 hours. Most hospital-acquired bloodstream infections are associated with central venous catheters, although bloodstream infections secondary to catheter-associated urinary tract infections and ventilator-associated pneumonia can occur.
Laboratory values can reveal evidence of organ dysfunctions and elucidate the possible source of infection. Signs of hypoperfusion apart from clinical exam may be evidenced by elevation of lactic acid, transaminases, prothrombin time, blood urea nitrogen and serum creatinine. Other findings include bandemia with normal or elevated white cell counts, leukopenia, thrombocytopenia, reduced mixed venous blood saturation, hypoglycemia, and hyperglycemia. Obtaining samples for cultures is vital in early identification of the pathogen, and it's antimicrobial susceptibility pattern to enable us to narrow down from broad-spectrum antibiotics to specific agents targeted towards these pathogens. Studies that do not inform clinical decision making are not recommended. If pretest probability is high for a hospital-acquired infection such as ventilator-associated pneumonia, then ancillary testing such as C-reactive protein and procalcitonin are not indicated. Recent guidelines from Infectious Diseases Society of Americal recommend noninvasive sampling with tracheal aspirates is enough due to non-inferior yield when compared to invasive samplings such as quantitative tracheal lavage or bronchoscopy. 
Management of sepsis should follow standard goals, which includes resuscitation with intravenous fluids and close monitoring for organ dysfunction with laboratory trends such as lactate. The clinical and hemodynamic response should be assessed with each fluid challenge. Adequate selection of empiric antibiotics and timely administration of antibiotics within the first hour has been shown to reduce mortality. Antibiotic treatment should be targeted based on risk factors for MDR organisms and clinical stability of the patient. When suspecting central line-associated bloodstream infection it is recommended to obtain two sets of blood cultures, one set each from the peripheral venous site and the central venous catheter site, ideally before initiating empiric intravenous antibiotics. If the patients had hypotension, hypoperfusion, and signs and symptoms of organ failure, the catheter must be removed and tip cultured as soon as possible. When suspecting catheter-associated urinary tract infections, remove the old catheter and obtain a urine sample for culture from a freshly placed catheter preferably before initiating antibiotics, to improve the yield of microbiological specimens. All catheters, including central venous catheters and urinary catheters, should be removed as soon as they are no longer indicated. A seven-day duration of antibiotics is recommended for hospital-acquired pneumonia and ventilator-associated pneumonia unless a longer duration is clinically indicated. For catheter-associated urinary tract infections, seven days of antibiotics are recommended if there is a clinical improvement, but if there is a delayed response or resulted in a bacteremia, the antibiotic course may be extended to 10 to 14 days. Antibiotic duration for central line-associated bloodstream infections is dependent on whether the infection is complicated or uncomplicated and whether the catheter is retained or removed. Complicated central line-associated bloodstream infections are associated with one or more of suppurative thrombophlebitis, osteomyelitis, endocarditis, persistent positive cultures after 72 hours and active malignancy or immunosuppression. 
Various preventive measures have been shown to reduce hospital-acquired infections. The major principles of prevention include hand hygiene, contact precautions when indicated, antibiotic stewardship to avoid rise of MDR organisms, appropriate antimicrobial prophylaxis particularly for surgeries, patient positioning, subglottic suction to avoid aspiration, strict asepsis when placing a central line, limiting unnecessary use of external devices, removal of catheters as soon as no longer indicated, and decontamination with chlorhexidine bathing for patients in the intensive care unit.
A Multidisciplinary Approach to Healthcare Associated Infections
Healthcare-associated infections have very high morbidity and mortality, costing the healthcare system billions of dollars each year. Over the years, many guidelines have been developed for monitoring, performing and monitoring central lines, and isolation of infected patients. Only a concerted effort by all healthcare team can have an impact. The primary strategy employed in hospitals is to prevent transmission of infectious agents among patients and healthcare providers. Nurses play a vital role in prevention as they are often the first to encounter infected patients. Washing hands and ensuring that everyone follows the established rules for infection prevention are key. Several category 1A recommendations including education of healthcare workers about infection control procedures, hand washing, using aseptic techniques when performing invasive procedures and securing catheters. Further, disinfection of hospital rooms and decreasing environmental contamination is also encouraged.  (Level I) Finally, with a rise in antibiotic resistance organisms, a hospital committee consisting of a pharmacist should be established to ensure that empirical use of antibiotics is not routine and ensuring that certain antibiotics cannot be used without prior approval from the committee.
Healthcare-associated infections are known to increase the length of stay, health care costs, and mortality. Each year close to 2 million healthcare-associated infections occur in the US resulting in nearly 100,000 deaths. The cost of care of these infections is at least $40 billion. Healthcare costs are known to occur in every medical and surgical department, including the ICU. However, with more awareness and better guidelines, both sepsis and central line infections appear to be declining. Best practices have now been established in most hospitals for insertion of central lines and wound care. (Level 1)