THE PLACE:

The neonatal intensive care unit (NICU) of an unidentified New Jersey hospital

THE SENARIO:

A newborn is diagnosed with a serious gram-negative bacterial infection. Further investigation reveals that several other infants in the NICU are colonized with the same organism (meaning the organism is found in or on the body, but is not causing illness). It is also found in cultures taken from air vents, sinks, respiratory and other equipment in the NICU. Clearly, a crisis is at hand.

The situation is far from unique. Hospital-acquired, or nosocomial, infections are on the rise in hospitals across the country, both large and small, community-based and urban. Some 5 to 10 percent of patients entering a hospital acquire a drug-resistant infection they did not have prior to admission. These infections are increasingly serious: The CDC estimates some 90,000 to 100,000 people die from them each year, and that it costs $4.6 billion per year to treat them. Nosocomial infections are now the fourth leading cause of death in the U.S., right after such other killers as stroke, cancer and heart disease.

Premature, low-birth-weight infants are among the most vulnerable to such infections, says Peter Wenger, MD, assistant professor of pediatrics and preventive medicine at UMDNJ-New Jersey Medical School (NJMS). These babies are at greatest risk for nosocomial infections due to the immaturity of their immune defenses. While isolation practices are of great help in controlling the spread of infection in the NICU, they do not eliminate the high risk of nosocomial infection in this population.

“Very premature babies have impaired resistance to infection,” Wenger explains. “Their skin is not formed, they have already had many interventions, including endotracheal intubation, urinary tract catheterization, and intravascular access, and they are often on multiple courses of antimicrobials.”

Pictured above is a 1000x magnification of a Gram stained sample from a blood culture of a patient septic with Enterococcus species, the long chain of medium, somewhat elongated Gram-positive (purple staining) cocci. These organisms are normal residents of the gastrointestinal and biliary tracts and of the vagina and male urethra. They are increasingly important causes of human disease because of their antimicrobial resistance.

Others who are vulnerable include the elderly and those with compromised immunity and/or chronic illnesses like diabetes and heart failure. Additional risk factors include gastrointestinal surgery, organ transplantation, exposure to medical devices, especially central venous catheters, prolonged hospital stay, and heavy exposure to broad-spectrum antimicrobial drugs.

Inter-institutional transfer of patients (say from one hospital to another, or from hospital to nursing home) also provides an increased opportunity for the rapid transmission of nosocomial infections from facility to facility, and in the worst-case scenario, to
communities at large.

“The hospital patient population has changed over the years,” says Wenger. “Only the sickest patients are admitted. Everyone else is treated at home. Those who are the sickest are more vulnerable to nosocomial infection.”

“There is a sense that these infections may actually be underreported,” adds Michele Burday, PhD, Director of the Division of Clinical Microbiology at UMDNJ-University Hospital (UH). “In community-based hospitals, patients are in and out so fast that many infections are missed, so it can be very difficult to track them.”

Antibiotic resistance

It’s estimated that 6 to 8 million antibiotic prescriptions were written unnecessarily for ear infections last year. By government estimates, about half of all antibiotic prescriptions are unwarranted. This overuse has serious repercussions. Eventually, bacteria “outsmart” the drug and mutate, acquiring resistance to the antibiotic.

Antibiotic resistance is not just the fault of overprescribing physicians. These medications are deeply ingrained in agricultural systems, both plant and animal. “Antibiotics are given to animals to fatten them up more quickly for the slaughterhouse,” says Wenger. “They’re in our fruits and vegetables, since fertilizers are developed from animal stools. They’re even in our pets: You can buy antibiotics for animals in any pet store, including tetracycline for fish.” Environmental bacteria that are exposed to antibiotics may develop resistance, and pass on that resistance to other bacteria that can infect humans.

The physician points out that contrary to popular belief, this is not purely an American phenomenon. Overseas, antibiotics are available over-the-counter. In some countries, you can even buy them right on the street. The result of these ubiquitous antibiotics: a new generation of “superbugs” is born.

“In many cases, antibiotic resistance is an end result of advanced medical care,” says Wenger. “The greater the use of antibiotics, the more likely you are to develop a resistant strain.”

Barry Kreiswirth, PhD, is director of the Public Health Research Institute’s initiative to track and control drug-resistant hospital infections across the state. Currently some 30 percent of New Jersey hospitals are participating in the program.

What’s happening in New Jersey

The New Jersey Department of Health and Senior Services collects data from hospitals around the state monitoring nosocomial infections and publishes a yearly report. The most recent is the Epidemiology Surveillance System 2001 Report (dated August 2003; www.state.nj.us/health/cd/episurv2001.pdf). Eighty-seven unidentified New Jersey hospitals participated in the survey.

The report identifies three organisms as being the most persistent and potentially dangerous. They are methicillin-resistant staphylococcus aureus (MRSA), vancomycin-resistant enterococci, and gram-negative enteric bacilli (which includes Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Acinetobacter baumannii and others). “Because of their resistance, these organisms present significant treatment issues,” says Burday.

Each has unique characteristics. Some are more inherently resistant than others, including Acinetobacter, which, Burday observes, seems to be somewhat specific to trauma units, and Enterococcus, which is not highly pathogenic but nonetheless is hard to get rid of.

The illnesses they cause vary, depending on what part of the body is infected. The most serious problems include pneumonia from infections transmitted by endotracheal intubation, bloodstream and urinary infections secondary to catheterization, and wound infections following trauma or surgery. MRSA is most likely to cause serious skin infections.

Above is a photo of a DNA fingerprintof M. tuberculosis strains from diseased tuberculosis patients. The Kreiswirth laboratory genetically characterizes bacterial isolates to determine their relatedness in support of infection control efforts.

“These are not run-of-the-mill infections,” says Wenger.” “The sickest population gets them.”According to the report, all three infections increased across the state from 2000 to 2001, with the largest increase (15.2 percent) being the gram-negative bacilli. E. coli, Enterobacter spp. and K. neumoniae accounted for 32 percent of all hospital acquired infections in 2001. The largest number of overall cases were MRSA, with a total of 3,903 blood isolates reported in New Jersey. Mortality rates for MRSA were high: 20 to 40 percent.

The report states: “The epidemiology of MRSA and the factors driving resistance bear strong similarities to those occurring with penicillin-resistant strains of S. aureus in the 1940s and 1950s. Soon after nosocomial penicillin-resistant S. aureus rates exceeded 40-50 percent, an upswing of community rates followed. The two rates reached virtually the same level by the 1970s.”

When all else fails

UH is part of a group of sentinel institutions that collect and share data on nosocomial infections. The information is maintained on a national database to which the institutions have access. Hospital personnel can look at national statistics, or compare their statistics with other hospitals in their region. The hospital also publishes an antimicrobic susceptibility report each year, listing statistics for common and uncommon infections, as well as their sensitivity to different antibiotics. While it is meant to be an internal guide to choosing the appropriate therapies for patients, it also gives insights into the breakdown of hospital-based infections and effectiveness of commonly used medications.
“There has been an increase both in number of infections and resistance,” says Burday. “Right now, some 40 percent of the S. aureus isolates we’re testing are methicillin resistant. Five years ago, that number was closer to 25 or 30 percent.”

This particular increase may have serious consequences. In the case of methicillin-resistant staph infections, there is only one drug left to treat the infection: vancomycin, an antibiotic with a significant toxicity profile. Sometimes referred to as the drug of last resort, it is used against organisms that are resistant to most other antibiotics.

The problem of “uncontrolled use” of vancomycin was the subject of much discussion at the International Conference on Nosocomial and Healthcare-Associated Infections, held in December 2003. It was reported that while the use of vancomycin has increased, several studies described delayed clinical response or “recalcitrance” in critically ill patients with MRSA infections.

At UH, protocols are in place to prevent overuse of some of the more powerful antibiotics. Checklists are used to be sure the right medications are being prescribed, and certain drugs cannot be given without the prior approval of an infectious disease specialist.

Surveillance strategies

While UH has a sophisticated lab capable of performing many different analyses, most smaller, community-based laboratories don’t have this capability. Other hospitals that are part of large health systems may even share laboratory facilities, leading to delays in recognizing resistant infections and stopping their spread.

In 2001, the state of New Jersey appropriated $1 million in funds to the Public Health Research Institute (PHRI), at the University’s International Center for Public Health at Science Park, for a program to track and control drug-resistant hospital infections. The program directors are Barry Kreiswirth, PhD, and Suzanne Lutwick, RN, MPH, both scientists at PHRI. Kreiswirth is an expert in DNA fingerprinting and other molecular
typing of infectious organisms, and Lutwick is an infectious disease epidemiologist.

The two have crisscrossed the state, meeting with NJ hospital officials to tell them about the program, called the Molecular Epidemiology Outbreak Center at PHRI. It was stablished as a support laboratory to genetically characterize both bacterial and fungal isolates for investigation of suspected cases of nosocomial transmissions.

“We are working very closely with hospitals to identify infections,” says Kreiswirth. “One of our strengths is that we have the tools to track ongoing problems.” These tools include genotyping isolates with high-tech molecular-based typing equipment in PHRI labs. Identical isolates from different patients can suggest that infections are spreading from person to person within the institution.

When a hospital suspects that there is an outbreak, a designated staff member can contact PHRI to discuss the problem. A primary specimen (usually either blood or sputum) is sent over to the Molecular Epidemiology Outbreak Center, where scientists will identify the organism and which antibiotics it will respond to. Suggested ‘next steps’ are discussed with hospital contacts.

For example, when the hospital with the outbreak in the NICU realized they had a problem, they sent isolates from all four patients to PHRI to determine if they shared the same DNA fingerprint. Testingconfirmed that the strains were genetically related to each other. By pinpointing the source of infections, interventions can be focused in a particular place. “You can’t eliminate hospital-based infections entirely,” says Kreiswirth.” But if two people in an ICU have staph infections, our goal is to prevent the patients around them from getting it too.”

One-third of the more than 80 hospitals in the state are currently participating in the program. “We take a strong stance on confidentiality,” says Lutwick. “We maintain our data without using names, so no person or institution is exposed.”

Prevention is Key

Experts estimate that one-third of nosocomial infections can be prevented, and billions of dollars saved, if good infection control practices are put in place. These include: improved surveillance of resistant organisms; judicious use and surveillance of antimicrobials; strict adherence to infection control procedures, including CDC guidelines for hospital hygiene; careful monitoring of IV lines, feeding tubes, and other interventions; isolation of patients with infections; and even the use of novel new infection-fighting vaccines.

“There is a vaccine for strep pneumonia, a common infection, and it could be offered hand-in-hand with the flu vaccine to those at risk,” says Beverlyann Collins, RN, MS, CIC, director of infection control at UH. “Unfortunately, many HMOs will not pay for it.” The Centers for Medicare & Medicaid Services (CMS), a Federal agency within the U.S. Department of Health and Human Services, recently removed restrictions on how the vaccine is administered and reimburses for it, and it is hoped that HMOs will follow suit.

While hand washing is the single most effective means of reducing hospital-based infections, numerous studies have demonstrated very low rates of compliance among healthcare workers. Says Collins: “Research indicates that only about 40 percent of healthcare workers wash their hands between patient visits, even when they know they are being observed.”

The CDC recently issued new guidelines for hand hygiene as a means of reducing infections in hospitals. This includes the use of alcohol-based cleaners, which are more effective than soap and water. While the CDC is not a regulatory agency, and has no authority to enforce the guidelines, The Joint Commission on Accreditation of Healthcare Organizations (JCAHO), the accrediting body for healthcare institutions, has come out strongly in favor of them, and has great influence in getting compliance from healthcare institutions.

Alcohol-based cleaners are being used in many hospitals, including UH, where they were implemented in 2002. Dispensers containing an alcohol-based antiseptic hand-washing gel are in each patient’s room. Nurses, physicians, technicians and anyone else who enters are directed to clean their hands before and after touching the patient or
anything in the room. The gel is rubbed on the hands; no water is needed and it does not dry out the skin. “Hand hygiene compliance is up, and this has had a positive effect on curtailing infections,” Collins states.

JCAHO has taken other initiatives in the battle against nosocomial infections, now directing hospitals to track and report death or significant harm to patients caused by hospital-acquired infections. The Centers for Medicare and Medicaid Services are also looking more closely at nosocomial infections. Both agencies are considering publishing specific data on hospital infections, including the institutions’ names, and making it available to the public. Collins adds that the information may become public by the end of 2004 or early 2005.

While infection prevention initiatives like hand washing may seem simplistic, they do work. The hospital with the outbreak in the NICU was advised to initiate the following interventions: add more hand washing stations, monitor staff to be sure they were practicing proper hand washing hygiene, and step up aggressive cleaning procedures, including more frequent decontamination of common use equipment. Within two weeks, the interventions were effective in stopping the spread of the bacterial cluster.

“But the bottom line is, antibiotics need to be used judiciously to preserve their effectiveness,” says Wenger. “As we’ve seen only too well throughout history, any antibiotic will eventually lose its effectiveness if it’s overused.”