Infectious Diseases Study (Healthcare Acquired Infections) PDF

Chapter 21 INTRODUCTION Infectious diseases have been plaguing the world for centuries. They are caused by pathogens---microorganisms that are capable of causing disease. For a pathogen to cause a disease, a susceptible host and a mode of transmission are required. A susceptible host usually has a...

Chapter 21 INTRODUCTION Infectious diseases have been plaguing the world for centuries. They are caused by pathogens---microorganisms that are capable of causing disease. For a pathogen to cause a disease, a susceptible host and a mode of transmission are required. A susceptible host usually has a weakened immune system or has had a breakdown in the body's defense mechanism. For an infection to be transmitted, a transport mechanism is required. Routes of transmission are contact, airborne, vehicle, and vector borne. Contact transmission occurs when a person or object comes in contact with a pathogen. Airborne transmission occurs when pathogens are carried through the air. Vehicle transmission is an indirect mode of transmission that occurs when a disease-carrying agent touches a person's body or is ingested. Similarly, vector-borne transmission is also an indirect mode of transmission that occurs when a vector, an organism that transmits a pathogen, bites or infects a person. Contact transmission is the most common mode of transmission. In this mode, pathogens are introduced into the body by direct or indirect contact. When an infectious disease is spread by direct contact, the microorganisms are transferred directly from person to person. In indirect-contact transmission, microorganisms are spread from a source to a susceptible host by passive transfer from an inanimate object or fomite, an object or substance capable of carrying an infectious organism. Often in healthcare settings, patients acquire infectious diseases through indirect contact via the unclean hands of healthcare workers, from contaminated equipment, or from the contaminated environment. Infections that are acquired in the hospital and were not present on admission are called nosocomial infections. A report by the Centers for Disease Control and Prevention (CDC) in 2018 revealed that nearly 1.7 million hospitalized patients annually acquire healthcare-associated infections (HAI) while being treated for other health issues and that more than 98,000 patients (one in 17) die due to these. The CDC 2020 National and State Healthcare-Associated Infections Progress Report includes the impact of COVID-19 on HAIs. COVID-19 surges increased rates of hospital-onset bloodstream infections and multidrug-resistant organisms, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), and gram-negative organisms. The 2020 CDC survey revealed a 47% increase in central line--associated bloodstream infections (CLABSI) overall, with a 65% increase in ICU patients. The report also indicated a 35% increase in ventilator-associated infections (VAE). There was a 5% to 11% decrease in surgical infections, and Clostridioides difficile infections were not significantly associated with COVID-19. A research study was conducted in 148 hospitals from March through September 2020 by the Infectious Diseases Society of America. The study revealed a 44% increase in MRSA, and a 43% increase in catheter-associated urinary tract infections (CAUTI). The Health and Human Services Department (HHS) had implemented an Action Plan to Prevent Healthcare-Associated Infections goal of decreasing HAIs by 25% by the year 2020. HHS is currently working to update this plan with new indicator targets and data, new research and intervention efforts, and a review of the impact of the COVID-19 public health emergency on HAIs. Multidrug-resistant organisms (MDROs) are common causes of nosocomial infections. Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), Clostridioides difficile (C. diff), Acinetobacter baumannii, and carbapenem-resistant Enterobacteriaceae (CRE) are all examples of MDROs that cause nosocomial infections. MULTIDRUG-RESISTANT ORGANISMS Methicillin-Resistant Staphylococcus Aureus MRSA infection is one of the leading causes of HAIs and is commonly associated with significant cost burden, morbidity, length of stay, and mortality. This involves both hospital-associated (HA-MRSA) infections and community-associated (CA-MRSA) infections. They differ not only in antibiotic susceptibility and treatment, but also in their clinical features and molecular biology. Epidemiology Staphylococcus aureus (S. aureus) is a common asymptomatic pathogen and is considered normal bacterial flora of humans. The 2019 CDC studies show that about one in three people carry S. aureus bacteria in their nose, usually without any illness, and most will not develop serious MRSA infections. Also noted in the report was approximately 30% of healthy individuals are colonized (the host carries the bacteria without active infection) with this pathogen in the nose, throat, axillae, toe webs, or perineum. Colonization can occur by touching the skin of another MRSA colonized person or touching a contaminated surface such as a countertop or door handle. If the skin is colonized, a MRSA infection can enter an open cut, scrape, or wound. Factors increasing risk for colonization include immunosuppression, prolonged hospitalizations, surgical wounds, intravenous sites, recent use of antibiotics, and being in close proximity to healthcare workers, patients, or family members who are MRSA colonized. The first case of MRSA was described in 1961, and the first documented outbreak occurred in the United States in 1968. From 2005 to 2012, MRSA bloodstream infections reduced by 17.1% each year. From 2013 to 2016, there was no significant change. The CDC and U.S. Department of Health and Human Services were working with healthcare facilities to meet the goals in the 2013 National Action Plan to Prevent HAIs and reduce bloodstream infections caused by MRSA by 50% by 2020 but have seen an increase of 44% of MRSA infections in 2020 due to the COVID-19 virus. Today, it is estimated that approximately 72% of S. aureus isolates from clinical cultures are MRSA. MRSA is the result of decades of unnecessary antibiotic use and is currently resistant to all beta-lactam antibiotics, including penicillins, cephalosporins, and carbapenems. It is also the most commonly identified MDRO pathogen in North America, South America, Europe, Asia, Africa, and the Middle East. In 2019, the CDC estimated that 9,000 deaths are caused by MRSA, and that MRSA is responsible for 70,000 severe infections per year. The 2022 data shows that mortality rates vary from 5% to 60% depending on the site of infections and the patient population. Despite having no healthcare risks, 60% of patients contract MRSA within 48 hours of hospitalization. A central line infection was the cause in 40% of patients. Historically, MRSA has been associated with healthcare; however, recently, a newer strain has been identified. The first case of community-acquired MRSA (CA-MRSA) was reported in the United States in 1980. CA-MRSA has become the most frequent cause of skin and soft tissue infections presenting to emergency departments in the United States. Hospital-acquired MRSA (HA-MRSA) tends to lead to more invasive diseases such as bloodstream infections, surgical-site infections, and pneumonia. Epidemiologically, HA-MRSA and CA-MRSA have different molecular characteristics. CA-MRSA strains are resistant to beta-lactam and macrolide antimicrobials; however, they remain susceptible to many non--beta-lactam antimicrobials. HA-MRSA strains are resistant to many other classes of antibiotics in addition to beta-lactam and macrolide antibiotics. Recent studies suggest that HA-MRSA and CA-MRSA should be treated on the basis of the type of infection and antibiotic susceptibility rather than the strain of bacteria. Risk factors for HA-MRSA include hospitalization in the past 18 months, soft tissue infection on hospital admission, hospitalization in intensive care, and residing in a long-term care facility. These factors increase the risk of exposure through invasive procedures or medical devices such as urinary catheters or IV lines that create a portal for the entry, including hemodialysis or surgery. Also implicated are recent or long-term broad-spectrum antibiotic therapy allowing bacteria to become resistant to a specific antibiotic. Oxacillin resistance has become increasingly common in these patients. Other risk factors include people with an immature or weakened immune system, such as young children, older adults, or people with HIV or AIDS, as well as other comorbid conditions such as diabetes, cancer, chronic obstructive pulmonary disease, congestive heart failure, and immunosuppression. Risk factors for CA-MRSA include children younger than 2 years of age, athletes, IV drug users, men who have sex with men, military personnel, and persons living in correctional facilities or shelters, sharing razors, needles or towels, or having contact with an MRSA-infected person. These risk factors are associated with close skin-to-skin contact, crowded living conditions, and poor hygiene (Table 21.1). Pathophysiology Staphylococcus aureus is an aerobic, gram-positive, nonsporulating (does not make spores capable of reproduction), coagulase-positive bacterium (produces the enzyme coagulase, which helps convert fibrinogen to fibrin). Because it is a coagulase bacterium, MRSA is coated with a fibrin wall that resists phagocytosis, making the bacterium more virulent, thus enabling it to protect itself from host defense mechanisms. Also, S. aureus has developed the ability to destroy the active lactam ring in the penicillin molecule by secreting an enzyme called beta-lactamase. This genetic mutation prevents the beta-lactam ring from binding to the bacterial cell; thus, the agent cannot exert its antimicrobial effects. MRSA is not naturally found in the environment, but it is found on humans. Staphylococcus aureus and MRSA can live on surfaces and humans for days to weeks; it has a varying life span. When a person is colonized with MRSA, the endogenous pathogen (the pathogen residing on the body) can easily be transferred to the skin and other body areas, increasing the risk for infection (Fig. 21.1). For example, if a person is colonized with MRSA in the nose and they wipe the nose with the hand and then touch an open wound, the bacteria can then be transferred to the wound and cause an infection. MRSA infections are also caused by exogenous (meaning "outside the body") sources. The mode of transmission from an exogenous source is contaminated surfaces. MRSA can be spread if an infected person touches the source of infection and then touches an object or surface. To prevent transmission from a contaminated surface, the CDC recommends covering cuts and open wounds with bandages and maintaining good hygiene, including bathing or showering regularly. The more common mode of transmission for MRSA is direct contact. MRSA is easily spread, especially in hospitals and healthcare settings, from patient to patient or from body part to body part on the unclean hands of healthcare personnel or through improperly cleaned equipment. Thus, proper hand hygiene is essential when caring for patients with MRSA. Contamination was from side rails, beds, supply carts, nurses' sleeves, stethoscopes, and the pockets of nurses' uniforms. Clinical Manifestations Clinical manifestations of S. aureus commonly include minor skin infections, including pimples, abscesses, sties, and impetigo. MRSA, on the other hand, causes more serious infections, including pneumonia, skin and soft tissue infections, surgical-site infections, and bloodstream infections. Complications Because MRSA is resistant to numerous antibiotics, infections can often be difficult to treat and can cause serious complications as well as widespread infection. Infections with MRSA are associated with increased morbidity and mortality rates. The MRSA mortality rate overall is 5% to 60%. The highest mortality rates of 50% were observed among patients with MRSA-related septic shock. Patients with MRSA pneumonia had a mortality rate at 50%, followed by MRSA endocarditis at 19.3%. MRSA bacteremia has a mortality rate of 15% to 60%, and the mortality of MRSA cellulitis is 6.1%. Patients with MRSA bacteremia have significantly longer lengths of stay, averaging 9.1 days, mainly in the intensive care units, and the average hospital cost is significantly higher. The costs of MRSA average \$60,000 per patient, with a total burden of \$10 billion yearly. Patients who develop MRSA surgical-site infections have a 3.4-times-higher risk of death than a non-MRSA patient, and hospital costs are twice as much as the average hospital stay. Patients colonized with MRSA from a previous hospital stay have a 29% greater risk for developing bacteremia, pneumonia, or soft tissue infection within 18 months of colonization. MRSA infections can also lead to osteomyelitis and toxic shock syndrome, and ultimately, untreated infections can lead to multisystem organ failure and death. Vancomycin-Resistant Enterococci Epidemiology Enterococci are bacteria that normally live in the gastrointestinal tract and the female genital tract and are also found in the environment in soil, water, and food. They are the third most common organisms seen in nosocomial infections. Traditionally, Enterococci have been considered low-grade pathogens; however, in the 1990s, they surfaced as an increasingly important cause of nosocomial infections. Enterococci are facultatively anaerobic (organisms that use aerobic metabolism if oxygen is present but can switch to anaerobic metabolism if oxygen is absent) gram-positive cocci. In the late 1980s, the increasing prevalence of MRSA, as well as the discovery of antibiotic-associated diarrhea, resulted in an increased use of vancomycin and the emergence of VRE. VRE were first reported in 1986 in Europe. The first case of VRE was reported in the United States in 1987. The exact origin of the vancomycin-resistant genes is unknown. Both Enterococcus faecalis and Enterococcus faecium are vancomycin-resistant species of Enterococci. Enterococcus faecium exhibits natural resistance to antimicrobial agents, including beta-lactams and aminoglycosides, and more than 95% of the VRE strains isolated in the United States are E. faecium. The majority of the remaining isolates are E. faecalis, which is a more pathogenic strain. Since the emergence of VRE in the 1980s, the rates of VRE colonization and infection have risen steadily. In the United States, VRE infections mostly occur in hospitals and are not associated with community acquisition. Nearly 30% of all healthcare-associated enterococcal infections are resistant to vancomycin, reducing treatment options, and there is a concern that the remaining drugs treating VRE may become less effective. VRE infections are associated with higher morbidity and mortality rates, higher healthcare costs, and prolonged lengths of hospital stay. In 2012, the CDC reported a decrease in VRE infections. In 2017, the CDC reported that VRE was the cause of 54,500 infections in U.S. hospitals, and the cause of 5,400 deaths. The 2022 COVID-19 special report by the CDC reveals that VRE cases increased 16% from 2019 to 2020, reversing substantial decreases since 2012. The prevalence of VRE is highest among patients who are critically ill in ICUs. High VRE rates are also seen in hematology patients and organ-transplant recipients secondary to immunosuppression. In solid organ transplant units, Enterococcus faecium is the most common cause of central line-associated bloodstream infections (CLABSIs), according to CDC's National Healthcare Safety Network. More than 70% of these E. faecium are resistant to vancomycin. Rates of VRE are significantly lower in western regions of the United States than in hospitals located in the eastern region. Larger hospitals or teaching centers also have significantly higher rates of VRE than smaller hospitals with fewer beds, secondary to increased severity of illness. Hand-hygiene compliance also affects the prevalence of VRE. Hospitals with observed hand-hygiene compliance rates at 59% or greater had significantly lower rates of VRE. Antibiotic stewardship is associated with lower rates of VRE. Efforts to reduce the use of vancomycin and cephalosporins have decreased the prevalence of VRE in the United States. The risk factors for VRE are very similar to those for MRSA. They include prolonged hospital stays, people with weakened immune systems (such as patients in ICUs, transplant patients, and cancer patients, especially hematological malignancies, prolonged exposure to antibiotics (especially exposure to vancomycin and cephalosporins), urinary tract infections (UTIs), and invasive procedures and devices. Severe comorbidities also are a risk factor for the acquisition of VRE (see Table 21.1). Pathophysiology VRE are hardy organisms and can remain viable on environmental surfaces for 7 days to 2 months. Although VRE are less virulent than MRSA, they can still cause many therapeutic problems because of their resistance to many antibiotics. They are spread by direct patient-to-patient contact or indirectly on the hands of healthcare personnel or on unclean patient care equipment. Once colonized, patients can remain colonized with VRE for prolonged periods of time ranging from 7 weeks to 3 years. People who are colonized can carry VRE on their body without symptoms and do not require antibiotics but colonization with VRE is associated with progression to VRE infection. Accordingly, there is a large emphasis on prevention because VRE outbreaks are very difficult to control owing to the fact that antibiotic use increases the microbial load of VRE and facilitates nosocomial transmission. They are also difficult to control because treatment options may be limited. A polypharmacological approach may be necessary. Clinical Manifestations Enterococci commonly cause UTIs, peritonitis (intra-abdominal and pelvic wound infections), and bacteremias; thus, clinical manifestations vary depending on the site of infection. Classic signs of UTI are back pain, pain on urination, the sensation of needing to urinate, and fever. Wound infections typically present as red and hot and, at times, with purulent drainage. Bacteremias present with signs of sepsis: tachycardia, hypotension, and fever. Complications One of the many complications of VRE is the growing list of resistance to antimicrobial agents as well as the emergence of vancomycin-resistant S. aureus. The vancomycin-resistant gene from VRE has been transferred to S. aureus isolates. This is quite disturbing because IV vancomycin is the medication of choice in the treatment of MRSA. Additional complications of VRE infections include prolonged hospital stays, prolonged antimicrobial therapy, higher attributable mortality rates, and increased cost of hospitalization. VRE bacteremia is associated with higher mortality rates than other Enterococci bacteremias because of antibiotic resistance. Additional complications of VRE are osteomyelitis, pneumonia, sepsis, and endocarditis. Enterococci are the third most common cause of infective endocarditis. This is a problem because no agent has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of VRE endocarditis. Clostridioides Difficile Epidemiology Clostridioides difficile (C. diff) was first detected in 1978. Increased use of antibiotics and the increased incidence of S. aureus infections are implicated in the emergence of C. diff. Clostridioides difficile is the most common cause of antibiotic-associated diarrhea in the United States, responsible for 15% of all hospital-acquired infections. The risk of recurrent C. diff infection (CDI) increases in patients who have already had one infection. Approximately 1 in 6 people who get C. diff infection will get it again in the subsequent 2 to 8 weeks. It is not known whether recurrence results from reinfection with a different strain or if it is the persistence of the strain responsible for the initial episode. The CDC identifies C. diff as one of the three most "urgent" threats to the public health system. In the mid-1990s, the incidence of C. diff in acute care hospitals was 30 to 40 cases per 100,000 patients. In 2001, the incidence had increased to almost 50 cases per 100,000 patients, and in 2005, it rose to 84 cases per 100,000. U.S. hospitals had a significant increase in C. diff infections between 2013 and 2014. An updated 2021 report by the CDC reveals that C. diff bacteria causes an inflammation of the colon and life-threatening diarrhea and colitis mostly in people who have had both recent medical care and antibiotics. The report continues with statistics of 223,900 infections per year, 12,800 deaths per year, and reports that approximately 29,000 patients die within 30 days of the initial diagnosis. This includes approximately 80% of patients aged 65 or older with a healthcare-associated C. difficile infection. Four to fifteen percent of healthy individuals are colonized with C. diff, and 3% to 21% of patients on admission to hospitals are colonized with C. diff without showing symptoms of the disease. Colonization occurs in the large intestine. The risk of colonization increases steadily each day during hospitalization secondary to the daily risk of exposure to C. diff spores in a healthcare setting. Newborns and children in the first year of life have some of the highest rates of colonization but not infection. The risk factors for C. diff infections include the use of antimicrobials, particularly clindamycin, cephalosporins, aminoglycosides, penicillins, and fluoroquinolones. Sixty percent of patients infected with C. diff have received antimicrobial therapy within the previous 3 months. Intravenous vancomycin was the most common treatment given. Other risk factors include duration of hospitalization; immunocompromising conditions; chemotherapy; nasogastric (NG) tubes, including feeding tubes; gastrointestinal surgery; severe underlying illness; and the use of acid-suppressing medications such as histamine-2 (H2) blockers and proton-pump inhibitors. The use of antimicrobial agents is a risk factor for C. diff infections because antimicrobials suppress the normal bowel flora and create an environment for C. diff to flourish. The greater the number of antimicrobials, the greater the number of doses, and the greater the duration of administration, the higher the risk of a C. diff infection. The use of acid-suppressing medications is a risk factor because these medications prevent the protective effect of stomach acid, which usually kills C. diff bacteria. Research shows that 31% of community-acquired CDI patients had proton pump inhibitor exposure but no antibiotic exposure. NG tubes and gastrointestinal surgery increase the risk for C. diff infections because NG tubes are usually inserted in patients who have had gastrointestinal surgery who then undergo prolonged periods of no oral caloric intake and who are prescribed prolonged courses of postoperative systemic antibiotics. These patients also suffer from impaired bowel motility, which increases the risk for C. diff infections (see Table 21.1). Pathophysiology Clostridioides difficile is a spore-forming, gram-positive anaerobic bacillus. Clostridioides difficile spores are resistant to many types of disinfectants, heat, and dryness. They also can live for months on surfaces, in skin folds, and on the hands of healthcare workers. They are transmitted through the oral-fecal route. This occurs when a pathogen from feces is introduced into the oral cavity of a host. Clostridioides difficile is almost exclusively found in healthcare settings. The hands of healthcare workers are the primary source by which C. diff is spread during outbreaks. Environmental contamination is also a means by which the organism is spread secondary to its ability to survive in the environment for long periods of time. It can also be spread by direct person-to-person contact; thus, a patient with C. diff must be put on contact-isolation precautions. Once a person becomes a susceptible host for C. diff by having one or more risk factors and has lost the protective normal flora in the colon secondary to antimicrobial therapy or decreased stomach acidity, its growth goes undetected and proliferates. The organism produces two toxins that cause the detrimental effects of the disease. One of the toxins produced is an enterotoxin, or toxin A, and the other toxin produced is a more potent cytotoxin, toxin B. Toxin A activates macrophages and mast cells, which release inflammatory mediators. The inflammatory mediators then cause disruption of the cell-wall junction, which results in increased permeability of the intestinal wall. Toxin B causes an increase in leukocytes and cytokines. Toxin B also causes degradation of the epithelial cells in the colon. Both toxins illicit a colonic inflammatory response that causes massive fluid secretions to move into the colon resulting in diarrhea. As the C. diff infection worsens, purulent and necrotic debris accumulates and forms pseudomembranes (thin tissue layer covering the surface of the epithelium). Clinical Manifestations People who develop C. diff infections test positive for C. diff toxins in their stool. Although patients may be asymptomatic, the most common clinical manifestation is loose, watery stools (\>3 stools in 24 hrs) and may have occult blood or mucus. Other manifestations may include abdominal pain and cramping. Fever has been observed in approximately 15% of cases. Fevers of \>101.3°F (38.5°C) have been reported in mild to severe C. diff. Complications Clostridioides difficile infections increase lengths of stay in healthcare facilities and reports estimate \$4.8 billion each year in excess healthcare costs for acute care facilities alone. The rising incidence of the disease is causing higher mortality rates related to the increasing virulence of C. diff strains and the increasing host vulnerability. C. diff may cause complications years after the resolution of the infection. Children have fewer complications than adults, and research shows that there are fewer complications with low-dose antibiotics such as oral vancomycin at 125 mg once daily and oral fidaxomicin at 200 mg once daily. Severe C. diff infections lead to complications such as: Volume depletion (hypovolemia) and hypotension (low blood pressure) Renal insufficiency Electrolyte imbalances (hypo-/hyperkalemia, hypo-/hypernatremia) Hypoalbuminemia (low serum albumin levels) Peritonitis (inflammation of the peritoneum) Paralytic ileus (intestinal obstruction) Toxic megacolon (rapid dilation of the large intestines) Fulminant pseudomembranous colitis Sepsis Death Complications are more common in patients with a white blood cell (WBC) count of 15.0 103/mm3 or higher, and catastrophic complications occur in patients with a WBC count of 50.0 103/mm3. Patients who are severely ill may require a subtotal colectomy (part of the colon is removed) with preservation of the rectum or colectomy (removal of the entire colon) for treatments for severe C. diff infections that progress to fulminant pseudomembranous colitis, paralytic ileus, toxic megacolon, or sepsis. Skin breakdown is also a complication of the disease. Excessive moisture, alkaline pH, colonization with microorganisms, and friction contribute to skin breakdown in patients with C. diff. Proper perineal cleansing is imperative. Creams and ointments that serve as a moisture barrier should be applied after cleaning to prevent skin breakdown. Fecal management systems can also be used in stool-incontinent patients to maintain skin integrity. Acinetobacter Baumannii Epidemiology Acinetobacter baumannii outbreaks have been experienced throughout the world; outbreaks were reported among U.S. military personnel dating back as far as the Korean War in 1955. This infection has emerged as an important healthcare--associated pathogen. In intensive care units particularly, it can cause pneumonia and urinary tract, wound and bloodstream infections. It was first identified in 1911 and was named Micrococcus calcoaceticus. In the 1950s, it became known as Acinetobacter. Acinetobacter is identified as an MDRO because it is resistant to more than three classes of antibiotics. It has been identified as resistant to not only the carbapenems beta-lactamase inhibitors pharmacology class, but also resistant to fluroquinolones, ampicillin/sulbactam, and trimethoprim/sulfamethoxazole (Bactrim), which reduces treatment options for the patient. In 2020, the CDC reported that carbapenem-resistant Acinetobacter caused an estimated 8,500 infections in hospitalized patients and 700 estimated deaths in the United States. The emergence of MDR Acinetobacter is due to the use of broad-spectrum antimicrobials and the transmission of strains among patients. The incidence of hospital-acquired infections is continually increasing. The CDC 2022 COVID-19 special report reveals an overall 35% increase in Carbapenem-resistant Acinetobacter, with a hospital-onset of 78%. It causes an increase in morbidity and mortality as well as an increased length of stay in that setting. Studies suggest that there is a very low prevalence of Acinetobacter in the non--critically ill medical-surgical patient population. The incidence of Acinetobacter infections is highest in ICUs with complex patients in the ICU having the highest risk. Acinetobacter infections rarely occur outside of healthcare settings, and healthy people rarely get serious infections from this organism; however, the prevalence and resistance of Acinetobacter are also increasing in the community. Research has shown that increasingly resistant strains of Acinetobacter are being introduced into nursing homes and long-term care facilities, which is concerning because there are fewer resources for infection surveillance and prevention in these settings. Risk factors for MDR A. baumannii infections and colonization include recent surgery, central venous catheters, tracheostomy, and mechanical ventilation. Other risk factors include enteral feedings, bed-ridden status, exposure to antimicrobial agents (esp. fluroquinolones, carbapenems), prior colonization with MRSA, hemodialysis, malignancy, prior glucocorticoid therapy, and underlying severity of illness. Vascular catheters and the respiratory tract have been identified as the most frequent source of Acinetobacter bacteremia. Other risk factors include prolonged hospitalization, ICU admissions, prior hospitalizations, and nursing home residence (see Table 21.1). Pathophysiology Multidrug-resistant Acinetobacter is a nonfermentative, aerobic, gram-negative coccobacillus that naturally inhabits water, soil, animals, and humans. It grows at varying temperatures and pH environments. More than 25 species within the Acinetobacter genus have been described. The most important species of this genus in human pathology is A. baumannii. It accounts for nearly 80% of Acinetobacter infections. It has been recovered from the skin, throat, and rectum of humans. It also colonizes the respiratory tract. This organism has the ability to survive for weeks to months on both dry and moist surfaces, which promotes transmission via contamination in hospital settings. The mechanism by which the Acinetobacter species become resistant to antimicrobials is an impermeable outer membrane, antimicrobial-inactivating enzymes, reduced access to bacterial targets, and mutations that change targets or cellular function. This organism is spread by direct or indirect contact. Direct transmission occurs when Acinetobacter is transferred from patient to patient without a contaminated intermediate object or person. This usually occurs when an infected Acinetobacter patient and noninfected patient share the same room. Indirect transmission occurs when Acinetobacter is transferred through a contaminated object or person. The most common mode of transmission is through the unclean hands of healthcare workers who have cared for infected or colonized patients. Transmission commonly occurs through contaminated skin, body fluids, equipment, or the environment. Multidrug-resistant Acinetobacter outbreaks are often traced back to common-source contamination. Respiratory care equipment, wound care procedures, humidifiers, and patient care items have been named as sources of contamination in recent outbreaks. Clinical Manifestations Acinetobacter can infect or colonize many body sites. Typical sites of colonization and infection are the respiratory tract, gastrointestinal tract, blood, pleural fluid, peritoneum, urinary tract, surgical wounds, central nervous system (CNS), skin, and eyes. The most frequent clinical manifestations of A. baumannii infections are ventilator-associated pneumonia and bloodstream infections. Complications Many complications are associated with MDR Acinetobacter infections. They increase mortality, morbidity, length of hospitalization, and length of ventilator days. Patients with Acinetobacter bacteremia have a 5-day excess length of mechanical ventilation compared with patients without Acinetobacter infections. These infections also prolong an ICU stay by 6 days, with the median duration of hospitalization being 18 days. Although difficult to prove secondary to the patient's severe underlying illnesses, the associated crude mortality rates range from 45% to 70% for MDR Acinetobacter infections. Carbapenem-Resistant Enterobacteriaceae (CRE) Epidemiology In 2022, the CDC reported about 12,700 CRE HAIs in the United States, with an overall hospital-onset infection increase of 35%. The CDC also reported that 50% of hospital patients who develop bloodstream infections from CRE bacteria die from them. Due to this, the CDC has labeled CRE an "urgent" concern, the CDC's highest level of concern. Enterobacteriaceae can cause infections in people in both the hospital and community setting. Healthy people are typically not at risk. Risk factors are similar to those for other MDROs. They include any disorder or treatment that disturbs the body's natural flora. There is an increased frequency in older individuals, patients in hospitals and long-term care facilities, patients with urinary catheters, intravenous catheters, feeding tubes, mechanical ventilation, and long-term antibiotic therapy. There is a slight increase in women. Common comorbidities include diabetes, heart disease, and renal disease. Pathophysiology Enterobacteriaceae include Klebsiella species and Escherichia coli (E. coli). These organisms are normally found in the intestines, where they are typically harmless if contained, but if spread outside the intestine, they can cause serious infections, such as UTIs, bloodstream infections, wound infections, pneumonia, and meningitis. Infections with CRE are usually spread through direct contact with infected or colonized people, particularly contact with skin, wounds, or stool. The resistance of CRE to carbapenems is caused by two main mechanisms: (1) the activity of β-lactamase enzymes that results in resistance to β-lactam antibiotics and (2) the production of carbapenemases, enzymes that hydrolyze (break down compounds in a reaction with water) carbapenem antibiotics. Clinical Manifestations Manifestations vary depending on the location of the infection---bloodstream, pneumonia, wound infections, meningitis, or UTIs. Common manifestations include fever, chills, and signs of sepsis if the infection has not been successfully controlled. Complications CRE are strains of bacteria that are resistant to carbapenem, a class of antibiotics typically used as a last resort for treating severe infections when other antibiotics have failed. These organisms are particularly dangerous and difficult because they have become resistant to nearly all available antibiotics. Because of this, mortality is high, especially in hospitalized patients. INTERPROFESSIONAL MANAGEMENT OF MULTIDRUG-RESISTANT ORGANISMS Medical Management Diagnosis Diagnosis of MDROs begins with detection. Bacterial culture is the recognized standard for MDRO diagnosis. However, recent clinical research has found that the positive rate of bacterial culture was only 15%, which delays the treatment of MDRO patients. Patients with MDRO infections are more resistant to antibiotic therapy, which can delay effective treatment. In an effort to contain outbreaks of VRE and MRSA, hospitals have initiated surveillance programs. A recent study suggests that lower rates of MRSA were found in healthcare settings where surveillance for antimicrobial-resistant organisms occurred. There is an MRSA risk assessment tool that is used to identify baseline data on MRSA incidence, prevalence, and transmission. The risk assessment helps to identify patient populations that are likely to be colonized or infected with MRSA. The purpose of the MRSA risk assessment is to prevent transmission through the development of a plan that is based on facility data and conditions. Thus, MRSA patient screening or active surveillance testing (AST) is individualized for each institution. With AST, MRSA cultures are obtained from patient populations identified as being at risk through the MRSA risk assessment. The most commonly cultured site is the anterior nares. Other sites that are typically screened for MRSA are areas of skin breakdown and draining wounds. Tracking VRE colonization is done through active surveillance in high-risk populations. Some institutions perform VRE screening on any patient admitted to the intensive care environment. The screening is done through the collection of perianal specimens. These specimens are obtained by swabbing back and forth across the perianal region using culture swabs; if stool is present, the culture swab should be immersed in the stool. There is no current surveillance for C. diff or Acinetobacter. If a patient is suspected of having C. diff secondary to watery diarrhea, a stool sample should be obtained. It is not recommended to test the stool of asymptomatic patients because infection is not likely. Once collected, the stool sample must be promptly sent to the laboratory. The C. diff toxins are unstable at room temperature, and false-negative results may occur in samples that are not tested within 2 hours of collection. Clostridioides difficile can also be diagnosed through direct visualization of the pseudomembranes via sigmoidoscopy or colonoscopy because it is nearly the exclusive cause of pseudomembranous colitis. Currently, there are no specific recommendations regarding best practice for surveillance cultures for Acinetobacter because of the lack of verified effectiveness of screening cultures. However, in an outbreak situation, screening cultures may be a part of an enhanced intervention when rates are increasing. Suggested body sites for screening cultures include the nose, throat, skin sites such as the axilla or groin, the rectum, open wounds, and endotracheal aspirates. When environmental contaminants are suspected of playing a role in an outbreak, environmental or equipment culturing may be used. At present, there is no active screening for CRE. Infections are typically identified through blood, wound, sputum, or urine cultures. Treatment Hand Hygiene The best treatment of MDROs begins with prevention---hand hygiene. The declining rates of some MDRO infections have been attributed to the use of alcohol-based hand rubs and improved hand-hygiene programs. It is important to remember that alcohol-based hand rubs are not effective against C. diff. Isolation Patients in healthcare settings who are either colonized or infected with MDROs are placed on contact-isolation precautions (see Safety Alert: Isolation Precautions) to help reduce patient-to-patient spread of the organism within the hospital. Contact-isolation precautions include wearing gowns and gloves on entry to a patient's room, removing both the gown and gloves just prior to exiting, and performing proper hand hygiene before exiting. Past studies have shown that organisms remained on healthcare workers' isolation gowns, gloves, and hands before hand washing after caring for an infected or colonized patient. As noted previously, proper hand hygiene is essential with all MDROs. Patients colonized or infected with MDROs are placed in private rooms when available or placed in a room with other patients colonized or infected with the same organism. Contact-isolation precautions are typically continued throughout the duration of the hospital stay or, as in the case of C. diff, until the diarrhea has stopped. Discontinuation of contact precautions for MRSA patients may occur when clearance of the organism has been documented with three or more surveillance tests. Retesting patients to document clearance is commonly done 3 to 4 months after the last positive test result. However, some institutions consider MRSA-colonized patients to be colonized indefinitely. During large MDR Acinetobacter outbreaks, patients are usually placed in a specific area or unit. Sometimes, the closure of an entire ICU is warranted to halt transmission. Single patient rooms, and dedicated nursing and respiratory staff, as well as dedicated equipment, are used to prevent further transmission. Medications Methicillin-Resistant Staphylococcus Aureus The most commonly used medication for the treatment of infections caused by MRSA is vancomycin (Vancocin), administered either IV or orally. Serum levels of vancomycin must be monitored, especially in patients with renal failure. The trough level (blood sample drawn after a dose is given but immediately before the next dose) should be monitored at least weekly to avoid toxic doses and maintain therapeutic levels. If trough levels are too high, vancomycin can cause nephrotoxicity as well as ototoxicity. Weekly blood urea nitrogen (BUN) and serum creatinine tests are recommended to assess kidney function because of the nephrotoxicity. Linezolid (Zyvox) given IV or orally is another antibiotic commonly used to treat skin and soft tissue infections caused by MRSA. Linezolid is a synthetic antibiotic of the oxazolidinone class and is bacteriostatic (stops organism reproduction) against Enterococci and Staphylococci. Recent studies have demonstrated that linezolid is equally as effective as vancomycin (Vancocin) for patients with skin and soft tissue infections. Linezolid is given for 14 to 28 days depending on the infection. If it is given for more than 10 days, the patient should be monitored through evaluation of a complete blood count (CBC) for myelosuppression, including anemia, leukopenia, pancytopenia, and thrombocytopenia. Linezolid should be discontinued if bone marrow suppression occurs or worsens. Linezolid may also cause diarrhea, nausea, and vomiting. Serious CNS reactions can occur when Linezolid is used together with serotonergic psychiatric medications. Patients taking Linezolid should avoid foods with high tyramine content (such as aged cheeses, dried/processed meats, bananas, alcohol, caffeine-containing beverages, or soy sauce) and should report any vision changes to their healthcare provider. If optic neuropathy occurs, other therapy should be considered. IV daptomycin (Cubicin, Cubicin RF) and IV tigecycline (Tygacil) are used for the treatment of complicated skin and soft tissue infections caused by MRSA. Daptomycin is a cyclic lipopeptide that has an antimicrobial spectrum similar to that of linezolid and exhibits bactericidal activity (kills the organism) against gram-positive organisms. It is used for skin and soft tissue infections Patients receiving daptomycin should be monitored for muscle pain and weakness and should have weekly creatine phosphokinase (CPK) levels drawn to assess for rhabdomyolysis (the breakdown of muscle tissue--releasing proteins into the blood). Patients with renal insufficiency need to have more frequent CPK level monitoring. Tigecycline is in the glycylcycline antibiotic class that has extended-spectrum activity against gram-positive, gram-negative, and anaerobic microorganisms. Tigecycline may cause diarrhea, nausea, and vomiting. It also decreases the effectiveness of oral contraceptives, so female patients should be instructed to use an alternative method of contraception while receiving this therapy. Assess for rash occasionally during therapy to monitor for Stevens-Johnson Syndrome, a very rare toxic epidermal necrosis that causes the epidermis to separate from the dermis, typically because of a severe medication sensitivity. If administered prenatally or during early childhood, it may cause yellow-brown discoloration and softening of teeth and bones. Clindamycin (Cleocin) given IV, IM, or orally is one of the more commonly used antibiotics used to treat CA-MRSA infections. Clindamycin has activity against aerobic and anaerobic gram-positive organisms including MRSA. The most common side effects of clindamycin are diarrhea, and it can cause C. diff. Patients receiving clindamycin must be observed for eosinophil and systemic symptoms, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermis necrolysis. These can be life-threatening Sulfamethoxazole-trimethoprim (Bactrim) given IV or orally is also used to treat CA-MRSA skin and soft tissue infections. Dosing must be adjusted for patients with impaired renal function. The most common side effects are gastrointestinal (nausea, vomiting, loss of appetite). Life-threatening adverse reactions/side effects include acute afebrile neutrophilic dermatosis, Stevens-Johnson Syndrome, and toxic epidermal necrolysis. Sulfamethoxazole-trimethoprim can cause sun sensitivity, so instruct patients to use sunscreen when going out into the sun. Patients should also report signs of jaundice, somnolence, and confusion to their healthcare provider because sulfamethoxazole-trimethoprim can cause fulminant hepatic necrosis. It is also important to instruct patients to stay hydrated to prevent the formation of renal stones while taking this medication. Because MRSA has started to become resistant to many antibiotics, antibiotic stewardship must be practiced when prescribing medications. The CDC suggests that minor to moderate skin infections be treated with incision and drainage of abscesses without the use of antibiotics. Currently, there are no recommendations to treat MRSA colonization; however, some institutions provide decolonization therapy. Decolonization therapy is the administration of local antimicrobial or antiseptic agents alone or in conjunction with antimicrobial therapy. A typical therapy used to decolonize patients is 2% mupirocin (Bactroban) ointment administered intranasally; mupirocin ointment is often used along with chlorhexidine bathing to complete the decolonization process. Mupirocin ointment should not be used with other intranasal products, and contact with mupirocin ointment should be avoided with open wounds, burns, and eyes. It can also cause headaches, pharyngitis, and rhinitis. Vancomycin-Resistant Enterococci VRE infections are often difficult to treat and may require multiple antibiotics for treatment because most VRE isolates are resistant to penicillin and ampicillin. Susceptibility testing is recommended to verify the activity of the antimicrobial agent being used. Quinupristin-dalfopristin (Synercid) given via IV was the first antimicrobial agent available to treat VRE infections caused by E. faecium. Quinupristin-dalfopristin is a streptogramin and targets bacterial ribosomes, thereby inhibiting protein synthesis. The first dose of Synercid may be given prior to blood culture results. Dosages may need to be adjusted in patients with liver insufficiency or cirrhosis. The length of therapy depends on the type of infection. Common side effects of quinupristin-dalfopristin are joint pain, mild diarrhea, nausea and vomiting, and muscle pain. Generally, the two major treatments recommended for VRE are linezolid and daptomycin if VRE is highly resistant to other antimicrobial therapies. Although off-label, tigecycline is also used to treat VRE infections if the patient is intolerable to other treatments. Linezolid has activity against both E. faecium and non--E. faecium species. It is the only oral agent approved by the FDA for the treatment of infections caused by VRE. Daptomycin has been reported to be effective against more than 99.5% of VRE isolates. Tigecycline has in vitro activity against VRE, but clinical data are lacking for the treatment of VRE infections. Treatment for VRE colonization is not recommended because there is currently no antimicrobial agent available to eradicate VRE colonization. Another drug, chloramphenicol, has successfully treated VRE for many years. The dose is 50 to 100 mg/kg/day divided into doses every 6 hours (4 g/day max dose). The main warning of this drug is that it should not be a first-line agent when there are other options available due to its high incidence of toxicity and adverse effects, such as aplastic anemia or bone marrow suppression. An infectious-disease specialist should be consulted before initiating this drug. Clostridioides Difficile Before treatment for C. diff can begin, the suspected causative antibiotic must be stopped. In about 20% of patients, C. diff infection will resolve within 2 to 3 days of discontinuing the antibiotic to which the patient was previously exposed. Additionally, the use of antiperistaltic agents should be avoided because they may delay clearance of toxins from the colon and exacerbate toxin-induced colonic injury or precipitate ileus (an intestinal obstruction that results in the failure of intestinal contents to pass through) and toxic megacolon (a life-threatening complication of inflammatory bowel disease that causes rapid dilation of the large intestines, which results in septic shock). Oral vancomycin is considered the first-line agent for the treatment of an initial episode of severe C. diff because it causes prompt symptom resolution and there is a significantly lower risk of treatment failure. It is effective because it is not absorbed in the intestines and kills the bacteria at the site of the infection in the colon. When oral vancomycin is not appropriate for the treatment of severe C. diff because of a coexisting ileus or toxic megacolon, IV metronidazole is used. Fidaxomicin (Dificid) is also used to treat C. diff infections. It is a bactericidal agent against C. diff that inhibits RNA synthesis by RNA polymerases. Common side effects include nausea/vomiting, abdominal pain, and other gastrointestinal disorders. This medication is reserved for patients who have recurrent infections and probable vancomycin resistance. Oral metronidazole, once the treatment of choice, is an alternative if vancomycin or fidaxomicin is not available. Although vancomycin, metronidazole, and fidaxomicin are among the medications used to treat C. diff, they do little to prevent CDI recurrence. Recurrence of C. diff infections is seen in 40% to 60% of cases. Recurrence typically occurs 4 weeks after therapy has been completed. The recurrence rate for patients treated with metronidazole is 20.2%, and the recurrence rate for patients treated with vancomycin is 18.4%. Subsequent occurrences should be treated with vancomycin using a tapered regimen. In 2016, the FDA approved the monoclonal antibody bezlotoxumab (Zinplava). It is indicated in the reduction of the recurrence of C. diff in patients who are receiving antibacterial medication treatment for C. diff infection and are at high risk for C. diff recurrence. This monoclonal antibody binds to C. diff toxin B and neutralizes its effects. It is given as a single dose based on the patient's weight of 10 mg/kg and is administered by IV intermittent infusion over 60 minutes in a dedicated IV line. It is not administered IV push or bolus. The half-life is 19 days. Bezlotoxumab does not replace antibacterial treatment. The onset, peak, and duration are unknown. Probiotics (live bacteria and yeasts) are another treatment that is used supplementally. Probiotics have effectively reduced the incidence of simple antibiotic-associated diarrhea and are sometimes used to treat recurrent C. diff; however, their efficacy is inconsistent. Another potential treatment option for recurrent C. diff is immunoglobulin therapy, but there is limited evidence supporting the efficacy of its use. Because of the inadequacies of current therapies as reflected by the high recurrence rate, the search is on for new antibiotics that inhibit vegetative cells of C. diff while preserving colonic flora during treatment. Emerging as a treatment for recurring C. diff is fecal microbiota transplantation (FMT). The success rate of FMT in C. diff symptom resolution has been reported to be 81% to 94% in patients with recurrent disease. Fecal microbiota transplantation may restore the gut microbiota to create an environment resistant to C. diff. The treatment of FMT is indicated for patients who have had three or more occurrences of C. diff or who have had unsuccessful treatment with 6 to 8 weeks of vancomycin. Relatives who share similar microbiota are thought to be the most effective donors. The donor is screened for ova and parasites; HIV; and hepatitis A, B, and C. A stool culture and sensitivity may also be done. The fecal sample from the donor is combined with normal saline or water. Methods of administering the sample to the patient are NG (25--50 mL) or colonoscopic (250--500 mL). Although frozen FMT oral capsules appear to be a viable delivery method, their clinical availability is limited, and their cost-effectiveness is still to be determined. Although rare, the New England Journal of Medicine (2019) reported the first death from a fecal transplant in a hospital in Massachusetts. A 73-year-old man with a rare blood condition died from drug-resistant bacteria found in a fecal transplant. The transplant was made with fecal capsules from one donor. Acinetobacter Many different antimicrobial classes are used to treat MDR Acinetobacter; however, before treatment begins, susceptibility testing must occur because antibiotic resistance has increased over the last decade. Beta-lactamase inhibitors, especially sulbactams, possess the greatest intrinsic bactericidal activity against A. baumannii. Sulbactams, which in the United States are combined with ampicillin-sulbactam (Unasyn) given intravenously or intramuscularly, can be used for mild to severe cases of A. baumannii infections; however, the cure rate is only 67%. Better patient outcomes are associated with lower severity of illness. Ampicillin-sulbactam commonly causes diarrhea or a rash. It also decreases the effectiveness of oral contraceptives, so female patients should be instructed to use another form of contraception. Carbapenems given intravenously, such as imipenem/cilastatin (Primaxin IM, IV) and meropenem (Merrem IV), are some of the most important therapeutic options for serious infections caused by MDR Acinetobacter. They have excellent bactericidal activity; however, the increasing carbapenem resistance is creating therapeutic challenges. It still remains the treatment of choice if the isolates retain susceptibility. Dosages need to be adjusted for patients with renal impairment. Carbapenems commonly cause nausea and headaches. They are also implicated in the development of Stevens-Johnson syndrome. In 2020, the FDA approved imipenem/cilastatin/relebactam (Recarbrio) to treat a broad spectrum of bacteria including Acinetobacter baumannii. Recarbrio is under the pharmacological classes of carbapenems and beta lactamase inhibitors. The treatment is 1.25 g every 6 hours and is given via IV intermittent infusion over 30 minutes. Adverse reactions/side effects include C. diff associated diarrhea, anemia and hypersensitivity reactions including anaphylaxis. Patients must be observed for signs of anaphylaxis, including rash, wheezing, laryngeal edema, and pruritus. Have epinephrine nearby, discontinue the drug, and immediately notify the healthcare provider if adverse symptoms appear. Aminoglycoside agents such as IV tobramycin and IV amikacin are options for MDRO isolates that retain susceptibility. Tobramycin maintains the highest susceptibility rates, and amikacin susceptibility has been reported at 53%. It is imperative that tobramycin peak levels are drawn on time (30 minutes after IV administration and 1 hour after IM administration) and trough levels should be obtained every 3 to 4 days to maintain a therapeutic dose. Amikacin may cause nephrotoxicity and ototoxicity; thus, peak and trough levels should also be monitored to maintain a therapeutic dose. Tigecycline, a glycylcycline agent, also has bacteriostatic activity against MDR Acinetobacter. However, the development of resistance to tigecycline has been reported recently. Polymyxin agents are the most active agents in vitro against MDR Acinetobacter. They are cationic detergents that disrupt bacterial cell membranes, causing leakage of the cell contents, thus increasing permeability and leading to cell death. Polymyxin agents include Polymyxin B and Polymyxin E, which is also known as colistimethate sodium (Colistin). This class of medication has demonstrated its effectiveness as a treatment for highly drug-resistant gram-negative bacteria. The efficacy ranges from approximately 55% to more than 80%. Cure or improvement rates with colistin are 57% to 77% among severely ill patients. Resistance rates of MDR Acinetobacter for polymyxin agents are currently low. Polymyxin agents can be administered orally, intravenously, ophthalmically, intrathecally, or by inhalation. In the past, polymyxin agents could be administered intramuscularly, but the route was discontinued when aminoglycosides became available. Polymyxins are poorly absorbed in the gastrointestinal tract, and gastrointestinal side effects are rarely reported with oral agents. The most concerning adverse effect of intravenous polymyxins is nephrotoxicity, which has a high incidence. Renal dose adjustment is required for patients with renal impairment. Tetracycline agents, such as minocycline (Dynacin) and doxycycline (Doryx), are also used to treat MDR Acinetobacter infections. These agents can be given both intravenously and orally. Dosage and length of therapy vary depending on the type and severity of the infection. These agents decrease the effectiveness of oral contraceptives, so female patients should be instructed to use an alternative form of contraception. Tetracyclines also cause sun sensitivity, and patients should be instructed to use sunscreen when out in the sun for prolonged periods of time. It is recommended that tetracycline agents be taken, if prescribed orally, 1 hour before meals or 2 hours after meals to help with absorption. Adequate fluid hydration is also recommended to prevent esophageal irritation or ulcer. They may also cause gastrointestinal disturbances. CBC and liver and kidney function tests should be monitored if the patient is receiving chronic tetracycline therapy Carbapenem-Resistant Enterobacteriaceae Treatment options are limited because no one antibiotic regimen has been shown to be better than another. As with other infections, treatment is based on the susceptibility of the organism. What follows is an overview because treatment is tailored to meet individual needs based on type of infection, comorbidities, and possible medication interactions. For serious infections caused by Klebsiella, ceftazidime-avibactam (Avycaz -- third-generation cephalosporin/beta-lactamase inhibitor) and meropenem-vaborbactam (Vabomere -- carbapenem beta-lactamase inhibitor) are acceptable options. These medications are given intravenously. They both work through the inhibition of bacterial cell-wall synthesis. They have reliable dosing and greater susceptibility, but data are limited. Options when neither of these is used are polymyxin-based combinations such as polymyxin (colistin or polymyxin B) and meropenem. These medications are also given intravenously and work through the disruption of the organism's outer cell membrane. These medications are associated with renal toxicity and neurotoxicity. Renal function should be carefully monitored, and the patient should be assessed for signs of neurological dysfunction. Some signs are mild, such as dizziness, diplopia, and weakness, but some adverse effects can be very serious, such as ataxia, dysphagia, dysphonia, psychosis, coma, and neuromuscular blockade leading to apnea. Polymyxin-based combinations and plazomicin are also options for other types of CRE. Plazomicin (Zemdri) is an aminoglycoside and is given intravenously. It is associated with nephrotoxicity and ototoxicity, including hearing loss, tinnitus, and vertigo. Neuromuscular blockade is also associated with plazomicin. Nursing Management Assessment and Analysis The clinical manifestations seen with MDRO infections are consistent with typical signs of infection: fever, tachycardia, tachypnea, and hypovolemia. Diarrhea is the prominent manifestation of C. diff, and MRSA wound infections can be red and warm with purulent drainage. Nursing Diagnoses/Problem List Risk for deficient fluid volume related to C. diff infection Inadequate primary defenses related skin breakdown/damage to tissue integrity Ineffective airway clearance related to MDR pneumonia Alteration in comfort related to diarrhea and abdominal pain Risk for perineal skin breakdown related to frequent stools Impaired tissue integrity related to MDR wound infection Impaired urinary elimination: Frequency related to UTI secondary to an MDRO Acute pain related to wound infection secondary to an MDRO Nursing Interventions Assessments Vital signs Increased body temperature is an immune response to an infection. A person's body temperature rises to try to kill the bacteria or virus that is causing the infection. Increased heart rate can occur due to fever and metabolic rate increases or hypovolemia. Tachypnea can occur secondary to pneumonia from infection with an MDRO. Tachypnea is also caused secondary to a fever, which increases the metabolic rate, which then increases the work of breathing. Low blood pressure may indicate vasodilation due to systemic infection and hypovolemia. Hypovolemia can also occur secondary to fluid loss as a result of C. diff diarrhea. Oxygen saturation Monitor the patient's oxygen saturation. Decreased oxygen saturation can be a symptom of pneumonia caused by an MDRO. Pain Pain is the fifth vital sign. Monitor patients for increased pain. Increased pain can be a sign of infection caused by an MDRO; pain may also result from a fever. Skin turgor and mucous membranes Decreased skin turgor and dry mucous membranes can result from dehydration secondary to a C. diff infection. Urine output Decreased urine output is a sign of dehydration and can occur secondary to C. diff diarrhea or may indicate the presence of a systemic infection with an MDRO. It can also occur as an adverse side effect of antibiotics used to treat the infection. Wound or surgical sites An infected wound or surgical site caused by an MDRO may be red, swollen, painful, and warm to the touch and may have purulent drainage. Bowel movement frequency and consistency Increased bowel movement frequency can result in dehydration. When a person has a C. diff infection, the bacteria proliferate and cause the release of toxins, resulting in an inflammatory response in the colon, which causes fluid to be secreted into the colon, resulting in diarrhea. Skin integrity Monitor skin integrity to assess for skin breakdown or incontinence-associated dermatitis (IAD) secondary to C. diff diarrhea. Laboratory tests White blood cell (WBC) count An increased WBC count is seen as part of the immune response; a large increase in WBCs may occur in C. diff infections. Serum creatinine level Increased creatinine levels can occur when a patient is dehydrated or has an adverse reaction to antibiotic treatment, signaling decreased renal function. Electrolyte and albumin levels Electrolyte and albumin levels may be decreased or increased secondary to dehydration from a C. diff infection or any MDRO infection. Actions Hand hygiene To prevent the spread of MDROs: (1) alcohol-based cleansers are effective against nearly all MDROs, except C. diff; (2) physical hand washing with soap and water is necessary to remove C. diff. Place the patient on contact-isolation precautions. This helps to prevent the spread of MDROs. Administer medications as ordered: Administer antibiotics. Antibiotics help treat infection of an MDRO. Administer fever reducers. Fever reducers decrease fever and complications associated with increased metabolic rate and also increases comfort. Administer pain medications. Pain medications decrease pain from wound or surgical-site infection. Administer IV fluids or encourage the patient to drink fluids. This helps a patient rehydrate from loss of fluid secondary to diarrhea from C. diff infection or from infections with MDROs. Administer supplemental oxygen. Supplemental oxygen increases oxygen saturation secondary to MDR pneumonia. Administer chest physiotherapy. Chest physiotherapy mobilizes secretions in patients with MDR pneumonia and increases oxygen saturation. Encourage early mobilization. This helps to decrease the risk of atelectasis secondary to MDR pneumonia and promote overall patient conditioning. Stop administration of causative antimicrobial agent in those with a C. diff infection. This stops/decreases C. diff--associated diarrhea. Perform wound care as ordered. Treat wounds and surgical-site infections to promote wound healing. Cleanse perineum and apply moisture barriers. Cleaning prevents skin breakdown or IAD secondary to C. diff--associated diarrhea. Use fecal diversion or containment systems in the stool-incontinent patient. Prevent skin breakdown and increase comfort in C. diff patients. Encourage family visits and the use of the telephone and television. These help to prevent depression in a patient in isolation with an MDRO infection. Teaching Contact-isolation precautions and hand washing (see Evidence-Based Practice) Teach patient and visitors the importance of wearing gowns and gloves when entering the room and removing the gowns and gloves when exiting the patient's room; also teach them the importance of performing hand hygiene after removing the gown and gloves. Take antibiotics as prescribed. Antibiotics should be taken as prescribed, and the patient should finish the course of antibiotics to prevent the reoccurrence of MDR infections. Clinical manifestations of infection It is important that the patient and family are able to recognize the signs and symptoms of infection. Sun protection Be aware of antibiotics such as tetracyclines that create sun sensitivities. Avoid prolonged sun exposure, and wear sunscreen and appropriate clothing. Evaluating Care Outcomes Infections due to MDROs can usually be successfully treated with antimicrobial therapy. Once the infection has been treated, the patient's vital signs and laboratory values should return to within normal limits. Patients should know the importance of finishing their antibiotic regimen to prevent the reoccurrence of infection. Patients and families should also know the clinical manifestations of a reoccurring infection to know when to seek healthcare advice