THE EMERGENCE of AIDS, reemergence of tuberculosis, and growth of drug-resistant bacteria are a reminder that infectious diseases will always be with us. This article focuses on three dangerous infections that are prevalent in hospitalized patients:
- Panton-Valentine leukocidin positive methicillin-resistant Staphylococcus aureus (PVL-positive MRSA), a multidrug-resistant bacterium. The PVL name comes from the toxin the bacteria produce.
- Acinetobacter baumannii, a bacterium that's often resistant to multiple drugs, which affects soldiers serving in Iraq as well as hospitalized patients at home.
- Infections that develop as a result of antimicrobial therapy, such as Clostridium difficile.
The new MRSA threat
PVL-positive MRSA evolved in the community and is linked to a strain that caused a Staphylococcus epidemic in the 1960s. The PVL toxin can cause boils and abscesses in skin wounds. As PVL-positive MRSA becomes more common, empiric and prophylactic therapy must be reevaluated.
Cefazolin, the frontline drug for prophylaxis against surgical-site infections (SSIs), has a relatively narrow spectrum, and doesn't significantly alter the patient's flora. The drug is most effective when given within 1 hour before surgical incision, and can be used for a short duration, reducing the chances that the patient's normal flora will develop resistance.
Although cefazolin has been effective against the most common pathogens that cause SSI, the emergence of PVL-positive MRSA as normal skin flora among patients means that cefazolin must be reevaluated as the drug of choice for SSI prophylaxis. Unfortunately, drugs that are effective against PVL-positive MRSA, such as vancomycin, can't be infused rapidly and need to be administered 2 hours before surgery begins, limiting their usefulness in emergency surgeries.
The most commonly used drug for PVL-positive MRSA (for skin infections and SSI prophylaxis) is vancomycin, a very broad-spectrum antibiotic. Vancomycin is bacteriostatic, meaning it doesn't kill bacteria but prevents them from reproducing. In comparison, cefazolin is bacteriocidal, so it's still the drug of choice for SSIs in patients who don't have MRSA.
Besides causing skin infections and complicating SSI prevention, PVL-positive MRSA is causing a newer life-threatening complication that's being reported with increasing frequency—post-influenza PVL-positive MRSA pneumonia. Traditional S. aureus infections have long been identified as a common cause of post-influenza pneumonia because of the bacteria's fondness for colonizing the anterior nares. This colonization and subsequent microaspiration of the bacteria into the lungs is likely the mechanism of infection.
However, the introduction of the PVL-positive MRSA toxin into the equation moves the prognosis from serious to much more grave.1 In the lungs, the toxin can cause a necrotizing pneumonia, even in previously healthy patients. Early diagnosis of this infection is essential to patient survival. Monitor your patient for hemoptysis, hypotension, and signs and symptoms of severe sepsis following a flu-like illness, even if the patient is young and in good general health. Signs and symptoms generally match traditional influenza: fever, cough, chills, tachypnea, vomiting, chest pain, and loss of appetite.
In a patient with necrotizing pneumonia, chest X-rays often show multilobar infiltrates, usually accompanied by pleural effusions and, later, cavitation. Lab results include marked leukopenia and a very high C-reactive protein level (above 250 mg/L) that helps differentiate necrotizing pneumonia from viral infections. A sputum culture with Gram stain normally reveals sheets of staphylococcal-like Gram-positive cocci. Patients who also have diarrhea and are vomiting may be experiencing toxic shock syndrome.
Few antibiotic options are available for necrotizing pneumonia. Although the causative organism generally is sensitive to vancomycin, the drug is bacteriostatic with poor penetration into lung tissue, so another antibiotic (such as clindamycin or linezolid) may also be used.2 Provide supportive care.
Looking out for MRSA
When obtaining a history from a patient before surgery or from a patient who has an abscess, ask if the patient's ever been diagnosed with MRSA in the past. This is key to determining appropriate prophylactic or routine antimicrobial therapy.
Place a patient who's been identified as having MRSA on contact precautions. Pay special attention to hand hygiene, appropriate use of personal protective equipment, cleaning the environment, and cleaning equipment not dedicated to that patient. Follow your facility's guidelines on whether or not the patient can share a room with other patients with MRSA.
In the outpatient setting, attempt to identify anyone else in the household who may need treatment for active infections. Dogs and other animals can act as reservoirs for the PVL-positive strain and transmit the bacteria at high rates.
Stress basic personal hygiene practices to patients (including not sharing personal items such as towels and bar soap), wound care, and performing hand hygiene after dressing changes or contact with the wound. Assure patients that with good hygiene practices, they pose no threat to the health of loved ones or coworkers. Tell patients to report any new boils or abscesses to their healthcare provider and inform other healthcare providers of their history of MRSA.
A. baumannii: Battlefield survivor
Unlike some other resistant bacteria, A. baumannii, a Gram-negative bacterium, continues to develop resistance to newer drug regimens. This bacterium also has become endemic in some acute care settings, notably among soldiers serving in the Iraq war.
Long a bane in ICUs, A. baumannii can't be reliably treated with piperacillin/tazobactam, most third-generation cephalosporins, aminoglycosides, or fluoroquinolones. Now, the bacteria have developed resistance to broader-spectrum antibiotics such as the carbapenems, usually among the most effective group of antimicrobials for treating Gram-negative infections.3
A. baumannii is one of the few Gram-negative bacteria that survive in both wet and very dry environments. It can thrive on healthcare workers' hands, inside and outside hospital equipment such as mechanical ventilators, and in the cities and deserts of Iraq.
When physicians caring for soldiers serving in Iraq began to notice high rates of A. baumannii infections in their patients' wounds, they wondered if the bacteria came from soil contaminating traumatic wounds or if the bacteria were acquired in the military healthcare delivery system.
By August 2004, roughly 100 soldiers had acquired A. baumannii bloodstream infections.4 As the outbreak began to grow, it became apparent that it was driven by healthcare practices. The publicity generated by this outbreak led some people to believe that the military cases were introducing resistant A. baumannii into U.S. civilian hospitals. This may have happened a few times, but most A. baumannii strains were established in Western healthcare systems long before the current Iraq war.5
So why does A. baumannii thrive in healthcare settings? While MRSA is strongly linked to healthcare workers' hands, A. baumannii isn't limited to the skin, and can sustain itself in the environment before spreading to others.6-8
Some of the environmental surfaces implicated are quite novel. One outbreak of resistant A. baumannii was linked to the inside of medical equipment such as mechanical ventilators, and may have been spread by a fan inside the ventilator that wasn't in the patient's air flow—not something that's routinely cleaned at most facilities.9 With recent multicenter studies showing that even high-touch surfaces often aren't adequately cleaned, it's no surprise that such a versatile organism has begun to proliferate in ICUs.10
If you're caring for a patient with resistant A. baumannii, place the patient on contact precautions. Perform meticulous hand hygiene, and make sure that the patient's environment is thoroughly cleaned and that patient-care equipment is disinfected. A. baumannii is relatively sensitive to most disinfectants, so routine cleaning is effective. Antibiotics used to treat A. baumannii infections vary depending on the organism's degree of drug resistance. Many multidrug-resistant strains are treated with imipenem or tobramycin; strains resistant to these drugs can be treated with colistin, although some strains have been reported resistant to colistin.
Antibiotic overload: C. difficile proliferates
With multidrug-resistant organisms come antibiotics, and with antibiotics comes the proliferation of C. difficile, a Gram-positive rod. The most widely identified risk factor for C. difficile illness (CDI) is the use of antibiotics, which remove the normal intestinal flora and let C. difficile proliferate. Toxogenic strains of C. difficile can cause illness that ranges from a mild diarrhea to potentially fatal pseudomembranous colitis and toxic megacolon. Since the 1970s, C. difficile has caused problems in hospitals and skilled nursing facilities. But in the last 4 years, the epidemiology and profile of C. difficile has changed dramatically.11
The new strain is BI/NAP1, which constantly produces toxins. (Other toxin-producing strains of C. difficile have a mechanism that limits toxin production.) An epidemic of BI/NAP1 in Canada was reported to have killed 2,000 people, although that number is in dispute because the province wasn't tracking cases of the infection at the time. Between August 2004 (when tracking in Canada began) and August 2005, 409 of 5,113 patients with CDI died.12 A recent study found that this strain is more likely to form spores than other strains of C. difficile, making it harder to kill in the environment and more problematic for healthcare facilities.13
Nonmutant C. difficile doesn't cause disease in all patients who carry it in their intestinal tract. In neonates, C. difficile isn't considered a pathogen, and transmission risk isn't a concern in this population. (The bacteria have been found as intestinal flora in up to 70% of newborns while causing no acute illness.) Only toxin-producing strains are considered pathogenic.
But even the presence of a toxin-producing strain in the intestines doesn't mean that the patient will develop signs and symptoms. Up to 30% of hospitalized patients who receive antibiotics and have toxin-producing strains remain asymptomatic carriers. One reason may be that prolonged colonization with C. difficile is a protective factor against developing CDI, the new term for C. difficile-associated disease or CDAD.14
Almost all antibiotics except for aminoglycosides have been linked in one study or another with CDI, including vancomycin, which is used to treat CDI.15 Most experts feel that broad-spectrum antibiotics are more likely to disrupt the intestinal flora than antibiotics with a narrower spectrum, putting the patient at greater risk for developing CDI.
Diarrhea is the most common manifestation of CDI, although some patients produce solid stool. The disease is usually categorized by severity. Mild disease is defined as occasional non-bloody diarrhea with mild cramping and mild abdominal tenderness. Moderate to severe disease involves profuse diarrhea, fever, abdominal pain, and leukocytosis.16
Pseudomembranous colitis, a severe manifestation of C. difficile, is characterized by profuse, watery diarrhea with abdominal distension and pain. Stool may be positive for occult blood, but frank bleeding is rare.
Patients with severe colitis can progress to paralytic ileus and toxic megacolon. Once toxic megacolon develops, diarrhea will stop because peristalsis in the affected part of the intestine stops. The megacolon fills with waste material. The patient will have an acute abdomen, fever, and tachycardia. Other manifestations of severe CDI include sepsis, peritonitis, hypotension, volume depletion, electrolyte imbalances, elevated creatinine, and a white blood cell count more than 20 × 109/L.
For all stool-based testing, labs should accept only watery or loose stools when evaluating patients for clinical illness. (Solid stool doesn't allow testing for CDI.) Given the rates of colonization in hospitalized patients, the presence of toxin in formed stool in asymptomatic patients proves only colonization, not necessarily disease. Feces should be submitted within 2 hours of specimen collection or be refrigerated.
Recently released commercial polymerase chain reaction tests for CDI appear to be better than the existing enzyme-linked immunosorbent assays. Endoscopic evaluation is generally used for evaluation of pseudomembranous colitis.
Reducing CDI's spread
To prevent additional cases of CDI in an institution, use this three-pronged approach:
- Improve hand hygiene to stop disease transmission.
- Restrict the antibiotic linked to the outbreak.
- Eliminate reservoirs for the organism by thoroughly cleaning the patient's environment.
Most C. difficile transmission probably occurs on the hands of healthcare workers, who carry the bacteria contained in one patient's feces to the second patient's environment. Whether alcohol-based hand rubs should be used is still an open question because these rubs don't kill C. difficile in its dormant spore state, when it's surrounded by many protective layers. The CDC recommends against using alcohol-based hand rubs in an outbreak, but has no position on using these rubs in daily situations. Some institutions have switched from alcohol-based hand rubs to soap and water for use with patients known to have CDI. However, given the number of asymptomatic patients colonized with C. difficile who are potential reservoirs, it's unclear whether this approach would eliminate transmission entirely.
In some cases, CDI outbreaks have been interrupted by severe restrictions on the antibiotic implicated as the major risk factor for CDI development.17 However, many other outbreaks have continued after restrictions of the implicated antibiotic, suggesting that such restrictions alone aren't the solution.
Giving probiotics such as lactobacillus to patients taking antibiotics, another strategy for preventing CDI, hasn't been proven effective. Probiotics are microorganisms that, when administered in sufficient quantities, may improve health. The CDC is monitoring research on probiotics, but doesn't yet recommend them for preventing drug-resistant infections.
Because the environment is known to be a reservoir for C. difficile, keeping the patient's room clean is a priority. But many cleaners don't kill the organism in its spore form. Bleach has reduced CDI rates in some settings, but isn't suitable for widescale cleaning.18 However, the act of manual cleaning probably lowers the bioburden enough to reduce the risk of transmission.
Contaminated patient-care equipment also can transmit C. difficile. Patients with CDI should be placed on contact precautions, with equipment dedicated solely to each patient (or cleaned between patients).
If your patient develops diarrhea while taking antibiotics, or if a patient with a history of recent antibiotic use develops diarrhea, inform the healthcare provider. If the patient has fecal incontinence, be careful not to cross-contaminate patient care items, such as skin ointments. When contaminated items are used again on the patient, they could cause reinfection.
Food may contain C. difficile, although the role of food in transmitting the infection is minimal, and more research is needed.19
No consensus exists on the best treatment for CDI. Before the emergence of BI/NAP1, stopping the inciting antibiotics alone was moderately successful in treating CDI. Stopping the antibiotic use associated with the CDI can be challenging if the patient is taking antibiotics for a condition associated with high mortality and if antibiotic alternatives are extremely limited or nonexistent. In these cases, because BI/NAP1 is associated with rapid progression and high mortality, the decision to discontinue the inciting antibiotic can be very difficult.
Treatment for many diarrheal illnesses includes antiperistaltics, but this treatment can be deadly for patients with CDI. Slowing peristaltic action extends contact time with the toxin, worsening disease. The patient's drug regimen should be reviewed for drugs that have antiperistaltic properties (for example, opioids), and adjusted as necessary.
Before the emergence of the BI/NAP1 strain, metronidazole was as effective as oral vancomycin for treating CDI. The CDC recommended metronidazole as the first-line choice because of concerns over the rapid increase in vancomycin-resistant enterococcus. However, the emergence of BI/NAP1 and reports of increased treatment failure and relapse with metronidazole have led some experts and clinicians to reconsider the treatment choices. Resistance to metronidazole remains very rare, and the reported treatment failures are most likely due to poor immune response from the patient.
If the patient can't take oral medications, intracolonic vancomycin has been shown to be effective and is the first choice. Metronidazole may be given I.V., although this route of administration hasn't been studied extensively.
A review of alternative treatments for CDI found three promising options for preventing recurrences: tapered-dose vancomycin, lactobacillus, and fecal enemas.20 Also, a vaccine for CDI is in clinical trials and has been found to be highly immunogenic in healthy human volunteers.21 However, it's unclear who will be the target population for this vaccine if it's released, given C. difficile's spread into the community.
Between 12% and 24% of patients have a second episode of CDI within 2 months of their first episode, with higher recurrence rates among patients with the BI/NAP1 strain.22 The risk of recurrence goes up with each event.
Recurrence of CDI has three plausible explanations: treatment failure to eliminate vegetative C. difficile in the patient's intestines, reinfection of the patient with C. difficile, or spore recrudescence (reactivation). In one study, about half of all patients thought to have had a recurrence of CDI within 2 months were actually newly infected with a different strain.23 Reinfection with the same strain may occur even more frequently because the patient environment is likely to be contaminated with the patient's own strain. However, this type of reinfection can't be tested.
No lab test can evaluate whether treatment for CDI worked. Patients can continue to test positive for the toxin even after they've recovered, so once a patient is found to be positive for CDI, the value of additional testing is limited.
The clinical response to therapy is generally a discontinuation of diarrhea in 2 to 5 days. In febrile patients, the fever responds more rapidly, usually in 1 to 2 days. If the patient's condition worsens or symptoms don't lessen after 6 or 7 days of therapy, a surgical consult is indicated; the patient may need a colectomy. Treatment may need to be extended in patients who've had recurrences of CDI.
PVL-positive MRSA, multidrug-resistant A. baumannii, and C. difficile will be with us for the foreseeable future. Staff education, meticulous hand hygiene, and cleaning equipment between patient use can help control these infections. By staying vigilant, you can help reduce infection rates and recognize problems when they arise.
Protect yourself (and your patients) from influenza
Nonpandemic (seaonal) influenza kills 36,000 Americans and accounts for more than 200,000 hospitalizations each year. Hospitals with low seasonal influenza vaccination rates among healthcare providers have higher rates of patient deaths from healthcare-transmitted influenza than facilities with higher influenza vaccination rates among healthcare providers.24 The CDC highly encourages and recommends that all healthcare workers be vaccinated for both seasonal influenza and the H1N1 strain of influenza, to protect themselves, their families, and their patients (especially immunocompromised patients) from infection.
The following excuses for not getting the flu vaccine have been debunked:
- Fear of getting the flu from the vaccine. This excuse has been disproved by numerous studies. The injectable vaccine contains inactivated viral particles. The nasal flu vaccine contains a weakened live virus that can't cause disease.
- Fear of needles. Now that the flu vaccine is available as a nasal spray, this shouldn't be an issue. And fear of needles may be overstated: between 96% and 99% of healthcare providers receive other vaccines, such as for hepatitis B, that are administered by needle.
Healthcare providers may self-report low rates of influenza acquisition each season, but serologic evidence suggests otherwise.25 Up to 25% of healthcare workers each season have demonstrated serologic evidence of influenza infection, although only about half of these professionals reported mild or asymptomatic infection.
Interestingly, studies in Europe and the United States showed that flu immunization rates were lowest among nurses. Physicians and housekeeping staff had higher rates of immunization, refuting the argument that educational levels drive immunization rates.
Some healthcare institutions have turned to the "declination" in an attempt to boost rates. In facilities using this strategy, healthcare workers refusing vaccination for other than medical reasons must sign a statement acknowledging that they're putting their patients, self, and their family members at risk. In many settings, these declinations have improved vaccination rates dramatically.
1. Gillet Y, Issartel B, Vanhems P, et al. Association between Staphylococcus aureus
strains carrying gene for Panton-Valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients. Lancet
2. Wargo KA, Eiland EH. Appropriate antimicrobial therapy for community-acquired methicillin-resistant Staphylococcus aureus
carrying the Panton Valentine leukocidin genes. Clin Infect Dis
3. Gootz TD, Marra A. Acinetobacter baumannii:
an emerging multidrug-resistant threat. Expert Rev Anti Infect Ther
4. Centers for Disease Control and Prevention. Acinetobacter baumannii
infections among patients at military medical facilities treating injured U.S. service members, 2002–2004. MMWR Morb Mortal Wkly
5. Manikal VM, Landman D, Saurina G, Oydna E, Lal H, Quale J Endemic carbapenem-resistant Acinetobacter
species in Brooklyn, New York: citywide prevalence, interinstitutional spread, and relation to antibiotic usage. Clin Infect Dis
6. Villegas MV, Hartstein AI. Acinetobacter
outbreaks, 1977–2000. Infect Control Hosp Epidemiol
7. Webster C, Towner KJ, Humphreys H. Survival of Acinetobacter
on three clinically related inanimate surfaces. Infect Control Hosp Epidemiol
8. Griffith ME, Ceremuga JM, Ellis MW, et al. Acinetobacter
skin colonization of U.S. Army soldiers. Infect Control Hosp Epidemiol
9. Bernards AT, Harinck HI, Dijkshoorn L, van der Reijden TJ, van den Broek Pj. Persistent Acinetobacter baumannii
? Look inside your medical equipment. Infect Control Hosp Epidemiol
10. Carling PC, Parry MF, Von Beheren SM. Identifying opportunities to enhance environmental cleaning in 23 acute care hospitals. Infect Control Hosp Epidemiol
11. Severe Clostridium difficile
-associated disease in populations previously at low risk—four states, 2005. MMWR Morb Mortal Wkly
12. Eggertson L. Quebec's official numbers: 409 C. difficile
13. Akerlund T, Persson I, Unemo M, et al. Increased sporulation rate of epidemic Clostridium difficile
type 027/NAP1. J Clin Microbiol
14. Kyne L, Warny M, Qamar A, Kelly CP. Asymptomatic carriage of Clostridium difficile
and serum levels of IgG antibody against toxin A. N Engl J Med
15. Modena S, Bearelly D, Swartz K, Friedenberg FK. Clostridium difficile
among hospitalized patients receiving antibiotics: a case control study. Infect Control Hosp Epidemiol
16. Malnick SD, Zimhony O. Treatment of Clostridium difficile
-associated diarrhea. Ann Pharmacother
17. McNulty C, Logan M, Donald IP, et al. Successful control of Clostridium difficile
infection in an elderly care unit through use of a restrictive antibiotic policy. J Antimicrob Chemother
18. Sehulster L, Chinn RY. Guidelines for the environmental infection control in healthcare facilities. Recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee (HICPAC). MMWR
19. Songer JG, Trinh HT, Killgore GE, Thompson AD, McDonald LC, Limbago BM[W18]. Clostridium difficile
in retail meat products, USA, 2007. Emerg Infect Dis
20. Faust G, Langelier D, Haddad H, et al. Treatment of recurrent pseudomembranous colitis with stool transplantation: report of six cases. Can J Gastroenterol
21. Aslam S, Hamill R, Musher D. Treatment of Clostridium difficile
-associated disease: old therapies and new strategies. Lancet Infect Dis
22. Kaltsas A. Risk factors and clinical outcomes of ribotype 027 and of non-ribotype 027 strains of C. difficile
at an urban hospital. Abstract, 2009 Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology.
23. Wilcox MH, Fawley WN, Settle CD, Davidson A. Recurrence of symptoms in Clostridium difficile
infection—relapse or reinfection? J Hosp Infect
24. Potter J, Stott DJ, Roberts MA, et al. Influenza vaccination of healthcare workers in long-term care hospitals reduces the mortality of elderly patients. J Infect Dis
25. Carman WF, Elder AG, Wallace LA, et al. Effects of influenza vaccination of healthcare workers on mortality of elderly people in long-term care: a randomised controlled trial. Lancet