Among other challenges, clinicians have to deal with new multidrug-resistant bacterial infections.

CLEVELAND—The three-part paradigm of infection following organ transplantation should guide the nephrologist in assessing the risk and instituting appropriate prophylaxis and treatment of infection following kidney transplant, Robin Avery, MD, said at the Nephrology Update 2008 here.

Complicating the management of these infections, however, is the emergence of unusual organisms and resistant organisms that are susceptible to fewer antimicrobials, necessitating more frequent use of drugs of last resort.

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The classic timetable of infection following organ transplantation, as articulated by Dr. Robert Rubin over two decades ago, can be divided into three main periods: first month post-transplant, months 1 to 6, and after month 6. At any time, the risk can be deduced from knowing the time post-transplant, the prophylaxis administered, environmental exposures, and the net state of immunosuppression, said Dr. Avery, section head, Transplant Infectious Disease, Cleveland Clinic.

Rare but dangerous

“In recent years, we’ve had a number of very high-profile transmissions in the news,” she said. These include seronegative HIV transmission, seronegative hepatitis C transmission, West Nile virus, and lymphocytic choriomeningitis (LCM) virus.

“Thankfully these are rare. Unfortunately when they do occur, they are often associated with high morbidity and mortality,” she said. Therefore, they prompt discussion about the appropriate level of screening for pathogens in donors.

The answers are not always clear, Dr. Avery said. “For example, [in] the lymphocytic choriomeningitis situation…the donor’s family member, hamster, and recipient all tested positive for LCM virus, but the donor’s serology itself was negative,” she said. Additions to the current screening panel of pathogens in donors would be costly, and false positives may exclude some individuals who otherwise are appropriate donors.

First month post-transplant

In the first month post-transplant, the usual standard postoperative infections are the rule rather than opportunistic infections. These consist of line, lung, and wound infections. “Some are related to technical issues with the surgery itself, and some have to do with early reactivation of herpes simplex virus (HSV) or yeast. [Occasionally they involve] bacteremia or other unsuspected pathogens in the donor,” she said.

The rise of multidrug-resistant bacteria has complicated the management of post-transplant infection. “Methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, traditionally bad bugs, seem tame compared [with] some of the ones we’re dealing with now,” she said.

Infection with quinolone-resistant Escherichia coli or other gram-negative bacteria is becoming more common, and “therefore it’s important to get microbiologic confirmation and susceptibilities when treating urinary tract infection. Otherwise the patient may come back uroseptic, and it turns out [to be] ciprofloxacin-resistant,” she said.

ICUs are encountering carbapenem-resistant Acinetobacter and carbapenem-resistant Klebsiella (also known as carbapenemase-producing Klebsiella [KPC]), “which means resistance to imipenem and all standard antibiotics.” This means that these pathogens would respond only to amikacin, if that, or IV colistin or tigecycline, and some of these are nephrotoxic.

Imipenem has traditionally been a fallback to treat extended-spectrum beta-lactamase-producing E. coli and Klebsiella, but these organisms are now becoming resistant to imipenem. “We’re also seeing more fluconazole resistance in yeast; Candida krusei and Candida glabrata are on the rise, and these often require other azoles or echinocandins; we try not to use amphotericin if we can help it, but sometimes we are still forced to use amphotericin preparations,” she said.

Increasing resistance of influenza to traditional drugs (amantadine/rimantadine) has occurred over the past year, leaving oseltamivir and zanamivir as the most effective options for the time being.

The virulent epidemic strain of Clostridium difficile that struck in 2005 remains a problem in 2008, she said.