Antimicrobial Use in ICU Case File

Antimicrobial Use in ICU Case File

Eugene C. Toy, MD, Manuel Suarez, MD, FACCP, Terrence H. Liu, MD, MPH

Case 18:

A 74-year-old woman has been in the ICU for 8  days for the management of recurrent  urinary tract and blood-borne infections. She has a history of a cerebral vascular accident and residual neurological deficits and has been hospitalized for  the past 3 weeks. A nurse notifies you for a  temperature  of 39.4°C (102.92°F). On examination, her pulse rate is 100 beats/minute, respiratory rate is 22 breaths/minute, and blood pressure is 110/84 mm Hg. The patient is currently on the third day of ciprofloxacin for empiric treatment of her recurrent urinary tract infection. Her serum creatinine is 2.2 mg/dL. Her urine culture  reveals multidrug-resistant  (MDR) Acinetobacter baumannii and the blood culture  reveals the same organism  in addition to fungus.

⯈ What is the most appropriate next step in the management of this patient? 

⯈ What are the underlying processes that predispose to this condition? 

⯈ What are appropriate strategies in the prevention of this problem?

ANSWER TO CASE 18:

Antimicrobial Use in ICU

Summary: An elderly 74-year-old woman with a prolonged hospitalization now has a urinary tract infection and bacteremia with multidrug-resistant (MDR) bacteria. She has an elevated temperature despite antibiotic treatment and has developed fungemia as well.

• Next step: Administer appropriate therapy to cover the MDR bacterial infection and fungal infection.
• Underlying predisposing processes: The factors in this patient contributing to MDR bacterial and fungal infection are prolonged hospitalization, comorbid conditions, recurrent or persistent infections, relatively immunocompromised state, and previous antibiotic exposures.
• Prevention of resistance: Provide prompt broad-spectrum antibiotics for empiric therapy followed by antibiotic de-escalation after culture sensitivities become available and when patient shows good clinical responses to the initial therapy.

ANALYSIS

Objectives

1. To learn the principles of antimicrobial selection and treatment endpoints in ICU patients.
2. To learn antimicrobial treatment strategies that may reduce the occurrence of antimicrobial resistance.
3. To learn the supportive care that may improve responsiveness to antimicrobial treatment in the ICU population.

Considerations

This is a 74-year-old woman with significant residual neurologic deficits and renal insufficiency after suffering from a cerebral vascular accident. She has had a prolonged hospital course and is now in the ICU after contracting a nosocomial infection. She is currently on antibiotics but does not appear to be improving. When a patient does not respond to antimicrobial therapy, it is generally important to determine if another source of infection is present and/or if the antibiotic treatment regimen is inappropriate or insufficient against the microorganisms responsible for the infection. The culture results at this point are helpful in directing her management. Since the same bacteria is isolated from her urine and her blood stream, the infection is severe, systemic, and inadequately controlled with the current antimicrobial regimen. In addition, fungal species isolated on blood culture strongly suggests that fungal sepsis is contributing to the worsening clinical picture. Infection with drug-resistant organisms contributes to prolonged hospitalization, higher hospital costs, and a poorer prognosis. Unfortunately, this patient represents a common clinical scenario in many modern ICUs.

The most important first steps in this patient's management is selection of the correct antimicrobial agents and dosages based on the sensitivity spectrum of the cultured MDR A . baumannii and fungal species. Assistance from the institution's microbiology laboratory and infectious disease specialists should be sought out to coordinate the management of her complicated infections. The emergence of antibiotic-resistant bacteria is a significant problem in intensive care units. This resistance makes antimicrobial therapy more difficult as patient's disease process and illness severity continue to increase. The inappropriate administration of broad-spectrum antibiotics can lead to even more difficult-to-treat infections.

DEFINITIONS

NOSOCOMIAL INFECTIONS: Infections acquired in a health-care facility. Generally, the infectious organism is first cultured >48 hours after admission.

HEALTHCARE-ASSOCIATED INFECTIONS: Infections in patients with prior hospitalization for > 3 days within the past 90 days, transferred from nursing home, or history of exposure to transfusion/dialysis centers.

EMPIRIC ANTIBIOTIC THERAPY: Antibiotic therapy that is started without culture evidence of infection. The therapy is started based on clinical suspicion of infection based on physiologic parameters.

ANTIMICROBIAL DE-ESCALATION: The goals of the de-escalating strategy are to strike a balance between providing prompt, appropriate initial antimicrobial therapy and minimizing the emergence of antimicrobial resistance. Patients with suspected infections are treated with broad-spectrum antibiotics aimed at most probable organisms that are causing the infections with narrowing (or discontinuing altogether) of the antibiotic coverage as soon as culture results become available, or if no infections are documented. Similarly, duration of treatment may be shortened when patients with uncomplicated infections show clinical improvement/resolution.

ANTIBIOTIC RESISTANCE: The ability of microorganisms to grow in the presence of antibiotic levels that would normally suppress growth or kill susceptible bacteria.

Approach To:

Antimicrobial Use in the ICU

CLINICAL APPROACH

Nosocomial infections affect ICU patients with far greater frequency than patients residing elsewhere in the hospital. Consequently, antibiotics are one of the most common therapies utilized in the intensive care unit. Additionally, up to 70% of all nosocomial infections isolated in the ICU are due to MDR bacteria. The reason for this elevated level of drug-resistant infections is multifactorial. ICU patients have a more severe underlying disease processes, are crowded into small areas of the hospital, and are often malnourished and immunocompromised. They are more likely to be subjected to multiple invasive procedures including endotracheal tubes, indwelling urinary catheters, and central venous lines. In addition to patient-specific risk factors, there are other general factors such as excessive antimicrobial use, poor aseptic technique, and inadequate hand hygiene of health-care providers that contribute to the increased infectious risks. The inappropriate choice and duration of antibiotics therapy can also contribute to the problem by selecting for resistant bacteria overgrowth and infection.

Microbial resistance is increasing in both gram-negative and gram-positive bacteria. These bacteria strains have greater resistance to broad spectrum antibiotics. The inadequate empiric coverage of these resistant bacteria can lead to a higher morbidity and mortality. However, the inappropriate use of broad-spectrum antibiotics can lead to the increase in emergence of resistant bacteria. Thus, the challenge to the physician is to use antibiotics that will cover the resistant bacteria without overtreatment that can lead to resistance.

When a patient is septic, antibiotics must be initiated promptly, preferably, within 1 hour of diagnosis. Each hour of delay over the next 6 hours has been shown to contribute to a decrease in survival of 7.6%. For most septic patients, the culture results are not known at the time of the initial presentation; therefore, antibiotics are selected based on clinician's suspicions of the source of infection. The initial choices of the preemptive antimicrobial therapy need to adequately address the potential infective organisms to minimize the mortality associated with the infection. Inadequate initial therapy usually involves either the failure to cover a specific microbe or utilizing antibiotics to which the organism is resistant. Therefore, high-risk patients admitted to the ICU with serious infections should be treated aggressively with broad-spectrum antibiotics until the bacteria cultures are isolated. It is obligatory that before antibiotics are started, cultures should be obtained. Once the culture isolates with their associated antibiotic sensitivities are identified, the antimicrobial therapy should be immediately adjusted to more narrow-coverage antibiotics that have bactericidal activity against the bacteria. This de-escalation therapy allows for treatment of the infection while reducing the risk of antimicrobial resistance. Another key component in the selection of antibiotic choice is based on the basic pharmacokinetics (necessary dosage to achieve adequate levels, tissue penetrance, etc). This is important so that under-dosing does not occur, as this can lead to an increase in the emergence of resistant organisms. This is particularly important in patients with renal insufficiency; adjustments of drug dosing and frequency of administrations are often needed when patient are receiving hemodialysis.

Recognizing when patients are at high risk for developing MDR infections is important in selecting appropriate initial broad-spectrum antibiotics, and these high-risk patients include those who have had prior antibiotics treatments during their hospitalization, prolonged hospitalization, and indwelling devices (such as endotracheal tubes, central venous catheters, and urinary catheters). Infected highrisk patients should be started on combination broad-spectrum antibiotics based on presumed infectious sources and local antibiograms (Table 18-1).

Initial antibiotics are selected based on knowledge of the infection source. Antibiotics have different tissue penetrations and should be taken into account when treating infections. Source control of the infection, such as abscess drainage, should be performed immediately. The choice of antibiotics is somewhat dependent 

on the local hospital flora. Different resistance rates are found at different hospitals, so antibiograms that show local antibiotic susceptibility should be used as a guide for initiating therapy that will cover local resistance. Once the cultures return with antibiotic susceptibility, antibiotic therapy should be de-escalated in spectrum and duration.

If no organism is isolated after 72 hours, serious consideration should be given to stopping the antibiotic administration. In a study evaluating the duration of therapy in treating patients with ventilator-associated pneumonia (VAP), it was determined that treating patients for 8 days instead of the standard 15 days had no difference in mortality, but significantly reduced the incidence of MDR bacterial infection. Patients with spontaneous bacterial peritonitis receive no additional benefits from being treated for more than 5 days with cefotaxime (Claforan). For all other isolated organisms, the antibiotics should be stopped after a predetermined time course. This allows for shorter therapy with decreased likelihood of selecting resistant organisms. It is also more economical to not provide prolonged, unnecessary antibiotic therapy. However, these maneuvers must all be undertaken after taking into consideration with the patient's clinical status. If the patient continues to remain septic, or is clinically deteriorating, antibiotic administration can be prolonged. Likewise, patients who are immunocompromised or elderly may benefit from longer durations of antibiotics therapy.

There are other strategies that are used in the ICU to decrease infection rates. Specific strategies that have been shown to decrease the rate of central-lineassociated bloodstream infections (CLABSI) when used in combination include hand hygiene, the use of full sterile barriers during central-line insertion, skin antisepsis with 2% chlorhexidine solution, subclavian vein insertion site, chorhexidine-impregnated sponge dressings at the line sites, centralizing equipment in a central-line carts during catheter insertion, and daily assessment of centralline necessity. Strategies that may reduce ventilator-associated pneumonias include the elevation of the head of bed, protocols for sedation medications, and ventilation, which are associated with reduced ventilation days.

The early administration of enteral nutritional support also seems to decrease infection rates, allowing for less use of antibiotics. Studies comparing enteral feeding versus parental feeding indicate that there is a decrease in overall infections. Additionally, the use of enteral feeding allows for maintenance of nonspecific mechanisms of immune protection by maintaining gut epithelium. Normal gut epithelium provides for absorption of nutrients, exclusion of pathogenic organisms, production of mucus, and maintenance of normal gap junctions. These mechanisms all protect against potentially harmful bacteria. Not only does enteral feeding aid in nonspecific immune protection, but it also helps provide continued function of gut-associated lymphoid tissue (GALT) which is home to lymphocytes that can produce cytokines and immunoglobulins. All of these factors help provide improved immune function, thus decreasing the need for antibiotics.

CLINICAL CASE CORRELATION

• See also Case 17 (Meningitis/Encephalitis), Case 19 (Sepsis), and Case 20 (Immune-Compromised Patient With Sepsis). 

COMPREHENSION QUESTIONS

18.1 An 82-year-old woman is admitted to the ICU for presumed urosepsis. Her initial blood pressure is 80/50 mm Hg, heart rate is 110 beats/minute, and oxygen saturation is 100% on 2 L nasal cannula. Urine, blood, and sputum cultures were drawn in the emergency department. Her hemodynamics improve to 120/80 mm Hg and heart rate of 80 bpm after administration of 2 L of normal saline and remain stable. She is started on IV vancomycin. Three days later, all of her cultures return with no growth to date. The next step in management should be:

A. Continue IV vancomycin for 8 more days

B. Continue IV vancomycin for 3 more days

C. Switch to ciprofloxacin PO for 3 days

D. Discontinue antibiotics completely

E. Re-culture the patient

18.2  A 34-year-old man is seen in the emergency department with fever, chills, nausea, and vomiting 2 days after injecting heroin intravenously. Which of the following is the correct order of antibiotic management?

A. Obtain cultures, start specific monotherapy antibiotic, change to broadspectrum antibiotics if resistant bacteria are found.

B. Start broad-spectrum antibiotics, pan culture (blood, urine, sputum), narrow coverage after 72 hours.

C. Start broad-spectrum antibiotics, culture in 3 days if no improvement, de-escalate antibiotics based on culture results.

D. Obtain blood cultures and obtain a CT scan of the abdomen. If the CT is normal, observe the patient until cultures become available.

E. Pan culture, start broad-spectrum antibiotics, de-escalate after culture results return.

18.3  Which of the following measures decreases the risk of developing antibiotic resistance in the ICU?

A. Central-line skin preparation using povidone-iodine (Betadine)

B. Antibiotic de-escalation

C. Restricting broad-spectrum antibiotics usage

D. Continued antibiotic administration for 2 weeks

E. Using peripherally inserted central venous catheters (PICC) rather than standard central venous catheters

18.4  A 32-year-old woman with a history of poorly controlled Type 1 diabetes had a below knee amputation 2 months ago for gangrene of her foot. Her postoperative course was complicated by a UTI and pneumonia. Her amputation wound spontaneously opened 2 days ago and she was pan-cultured. Her wound was satisfactorily debrided in the operating room and she was started on IV vancomycin and IV piperacillin and tazobactam (Zosyn). She is now being transferred to the ICU for worsening hyperglycemia and dehydration. Her wound culture has grown methicillin-resistant Staphylococcus aureus (MRSA) that is sensitive to vancomycin. All other cultures were negative. What is the next step in management?

A. Glucose control and narrow her current coverage to vancomycin.

B. Glucose control; continue her current antibiotics and add cefepime.

C. Glucose control and continue her current regimen.

D. Stop her current antibiotics and perform above knee amputation for source control.

E. Continue current antibiotics and obtain additional cultures.

18.5  An 89-year-old woman who is significantly malnourished is in the ICU with Pseudomonas aeuriginosa pneumonia. She has received 5 days of antibiotics, but still has copious amounts of sputum and is continuing to require a significant amount of ventilatory support. The most appropriate course of action is:

A. Continue her current regimen, but re-culture for any spikes in temperature.

B. Discontinue her antibiotics on day 8 of therapy.

C. Broaden her antibiotics for the next 24 hours and then stop antibiotics.

D. Stop antibiotics, re-culture, and await culture results before re-starting antibiotic therapy.

E. Empirically add an antifungal agent.

ANSWERS TO QUESTIONS

18.1  D. This patient presented to the emergency department hypotensive and tachycardic and although it was initially thought that she might be septic, none of her cultures returned with any bacteria. Additionally, she improved with simple rehydration, indicating that she was possibly just dehydrated. Thus, there is no need of continuing her antibiotics. The continuation of her antibiotics could also lead to the formation of resistant bacteria.

18.2  E. It is essential to obtain cultures prior to starting antibiotic therapy for presumed sepsis. Although the unnecessary use of broad-spectrum antibiotics can lead to increased antimicrobial resistance, it is important that all bacteria are initially covered when starting empiric antibiotic therapy. Once the bacterial cultures return, the antibiotics can be de-escalated to the appropriate mono therapy.

18.3  B. The use of broad-spectrum antibiotics for prolonged duration contributes to the increase in antimicrobial resistance. However, their use is necessary in the initial empiric therapy to cover the majority of probable pathogens. Once the cultures have returned, the therapy can be de-escalated, so that the patient's infection can be appropriately treated and broad-spectrum antibiotics use can be limited. Using aseptic technique and limiting the duration of antibiotic administration also helps reduce antimicrobial proliferation and resistance. Chlorhexidine skin preparations have been shown to cause fewer central-line-associated infections in comparison to povidone-iodine (Betadine) skin preparations. The use of PICC in hospitalized patients has not been shown to be associated with reduced catheter-associated infections in comparison to standard central venous catheters.

18.4  A. The hyperglycemia can contribute to poor response to antimicrobial therapy in this patient and needs to be better managed. This patient has multiple risk factors for infection with resistant bacteria. Her wound has grown MRSA that is sensitive to vancomycin. This is the most likely source of her sepsis. The addition of piperacillin and tazobactam (Zosyn) does not provide additional benefits. Her wound has been recently inspected and debrided to satisfaction, therefore there is no indication at this time to perform an above the knee amputation. Fungal infections are reasonably common in relatively immunocompromised patients; however, there is no indication of this process at this time.

18.5  A. This is an elderly patient who is being treated for pneumonia. Although she is nearing the end of a standard 8-day course of antibiotics for ventilator associated pneumonia, she is malnourished and still requires a significant amount of ventilatory support. Because of her age and relative immune compromised status, it is reasonable to extend her antibiotics past the standard 8 days, with re-culturing if her temperatures spike through her current antibiotic coverage and continued vigilance for other causes of her fever.

CLINICAL PEARLS

⯈ Broad-spectrum antibiotics should be started on septic patients based on presumed location of infection and local antibiograms. 

⯈ Once culture sensitivities have returned, de-escalation of antibiotics should be done to minimize the use of broad-spectrum antibiotics. 

⯈ The duration of antibiotic administration should be  limited to specific time courses. If there is no growth of initial cultures after 72 hours, serious consideration should be given to discontinuing the antibiotics. 

⯈ Prolonged administration of antibiotics may be necessary in the elderly, immunocompromised, and clinic ally deteriorating patient. 

⯈ Nonpharmacologic strategies for decreasing need for antibiotics in the ICU include aseptic technique, hand-washing, and early enteral nutrition. 

References

ATS/IDSA. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am ] Resp Crit Care Med. 2005 ; 1 7 1 :3 88-4 1 6 . 

File TM, Jr. Recommendations for the treatment o f hospital-acquired and ventilator-associated pneumonia: review of recent international guidelines. Clin Infect Dis . 201 0;5 1 (suppl 1 ) :S42-S4 7 . 

Leone M , Martin C. How t o break the vicious circle o f antibiotic resistances? Current Opin Crit Care. 2008; 1 4 : 5 8 7 - 5 9 2 . 

Masterton R G . Antibiotic de-escalation. Crit Care Clin . 20 1 1 ; 2 7 : 149 - 1 62 . 

Niederman M S . De-escalation therapy i n ventilator-associated pneumonia. Curr Opin Crit Care . 2006 ; 1 2:452-45 7. 

Volles DF, Brana TN. Antibiotics in the ICU: focus o n agents for resistant pathogens. Emerg Med Clin N Am . 2008;26:8 1 3 - 834.

HomeCritical Care Case FileAntimicrobial Use in ICU Case File