I thought I was done for the time being with “nightmare bacteria” (the US CDC’s characterization of disease organisms resistant to the last-ditch antibiotics called carbapenems), but there are two stories today that deserve to be called out as examples of how rapidly and dangerously these pathogens are spreading.
What makes hospital-acquired infections so intractable? There’s no question that some of the organisms that cause them are tricky: MRSA hangs out on the skin and and in the nostrils, and E. coli resides in the gut, making it easy for them to be carried into hospitals undetected. Hospital workers’ poor performance on hand-washing is well-documented. And recently, researchers have begun to wonder whether hospitals have missed an opportunity by not emphasizing environmental cleaning —- of rooms, computers and equipment, for instance -— given how persistently some bacteria can linger.
A new paper in PLoS One, though, says there’s another factor contributing to the problem, one that has missed consideration until now: weather. An 8-year study of infection data from 132 hospitals finds that as outside temperatures rise, in-hospital infections with some of the most problematic pathogens rise also.
The analysis is a warning to healthcare institutions to be additionally on guard when it is warm outside. But the authors say it’s also a warning to the rest of us: If global climate change raises ambient temperatures, it could increase the likelihood of deadly hospital infections as well.
Back in June, there was an unnerving report from the Centers for Disease Control and Prevention that NDM-1, the “Indian supergene” that renders common hospital-acquired infections practically untreatable, had been found in the military hospital at Bagram Air Base in Afghanistan.
The gene was being carried by a gut bacterium, Providencia stuartii, that was causing septicemia in an Afghan national who had been taken in by the military hospital. The particular strain of NDM-1 could be treated only by a single drug, aztreonam; it was resistant to everything else. Unsurprisingly, the victim died.
Though it wasn’t explicitly stated, the subtext of the CDC’s brief bulletin was clear: By extending compassion to the local resident (who was badly burned and had been treated at a hospital in Kabul), the military staff had brought into their hospital a highly resistant organism that could endanger their troops. It made me wonder, at the time, how often this happened, and what the consequences might be.
A study performed at Bagram, and published this month in Infection Control and Hospital Epidemiology, supplies an answer, and it’s a troubling one.
File under: Really not good news.
Deep in the back of the weekly bulletin of the Centers for Disease Control and Prevention, there is a note that NDM-1, the “Indian supergene,” has been isolated from a patient in a U.S. military field hospital in Bagram, Afghanistan.
It’s been a few months since NDM-1 was in the news, so let’s recap. The acronym (for “New Delhi metallo-beta-lactamase 1”) indicates an enzyme that allows common gut bacteria to denature almost all the drugs that can be used against them, leaving two or three that are inefficient or toxic. It was first identified in a resident of Sweden, of Indian origin, who had returned to India for a visit, was hospitalized there, went back to Sweden, and was hospitalized again.
A set of papers published this month in two journals provide an unsettling glimpse into the rocketing incidence and complex epidemiology of one really scary pathogen, Acinetobacter baumanii.
In the all-star annals of resistant bugs, A. baumanii is an underappreciated player. If people — other than, you know, disease geeks — recognize it, that is because it’s become known in the past few years for its propensity to attack wounded veterans shipped to military hospitals from Iraq and Afghanistan, earning it the nickname “Iraqibacter.” (Important note: Steve Silberman of Wired magazine took an early look at this phenomenon in 2007, in a great story that analyzed the epidemiology of Iraqibacter to show that military infection control, not the environment of Iraq, was to blame for the bug’s rapid emergence.) A. baumanii is a nasty bug, causing not just wound infections but pneumonia, urinary tract infections, meningitis and bacteremia. Even more nasty, it collects resistance factors like baseball cards, and is commonly resistant to at least 4 antibiotic classes. The most resistant strains are susceptible only to the so-toxic-we-put-it-back-on-the-shelf-decades-ago antibiotic colistin.
This is a particular concern because A. baumanii is a Gram-negative bacterium — and while the drug-development pipeline for Gram-positives such as MRSA has slowed practically to a trickle, the one for Gram-negatives has dripped itself dry. As the Infectious Diseases Society of America and Jerome Groopman of the New Yorker highlighted back in 2008, drugs for Gram-negatives are barely on the agenda for the few companies still conducting antibiotic development.
So, the first piece of bad news. In Infection Control and Hospital Epidemiology (ICHE), a team from Brooke Army Medical Center in San Antonio take a look at their incidence of resistant Ab and find it exploding. Between 2001 and 2008, the percentage of A. baumanii isolates that were resistant to at least 3 classes of drugs went from 4% to 55%; of all the isolates, 17% (127) were resistant to at least 4 drug classes, and one was resistant to, well, everything.
How does A. baumanii spread so fast? A second paper in ICHE suggests a reason: The bug seems to do a better job than other resistant pathogens of contaminating the gear and hands of health care workers. A study done at University of Maryland found that when health care workers took care of A. baumanii patients, they ended up with contaminated gowns and gloves 39% of the time, and with contaminated hands (after glove removal) 4.5% of the time. Those are higher rates than for MRSA (18.5% of encounters) or VRE (8.5%).
A review article in Clinical Infectious Diseases reminds us why we should care about this: It examines the drugs to which some strains of A. baumanii are still susceptible, and finds all of them significantly toxic to different organs (kidneys, liver, pancreas, red blood cells, ) at the doses necessary to wipe out the bug.
Which is all troubling by itself. But a paper and editorial also appearing in Clinical Infectious Diseases make the case for A. baumanii as a bigger threat than has been understood. The bug’s recent epidemiology has shown a distinct split, between the highly resistant forms affecting veterans, most of them being treated in the military evacuation chain, and less-resistant forms affecting civilians in hospitals (including in the Brooks data in the paper above). The severe wounds, aggressive treatment and rapid multiple transfers of personnel in the military system inadvertently created an environment that not only put A. baumanii under great selective pressure, but also spread it with startling efficiency.
The paper, reporting data from 4 community hospitals near Detroit, shows that the civilian medical system — that would be the one that most of us live in — has duplicated that churning as well. Between 2003 and 2008, all A. baumanii in their network increased 25%. A. baumanii resistant to the first 2 front-line drugs went from 2% to 33% of isolates. And “pan-resistant” A. baumanii — resistant to all 8 drugs available for it, an essentially untreatable strain — went from nonexistent to 14% of all the isolates that network found.
The effect on the patients was dramatic, of course: The more resistant their strains were, the more likely they were to never go home from the hospital, but (if they did not die there) to be discharged instead to a nursing home, long-term acute care facility, or hospice. But the larger point is that they carried that multiply-resistant strain with them, distributing it throughout the region: Patients came to those 4 hospitals, carrying A. baumanii, from 17 different nursing homes; from the 4 hospitals, carrying A. baumanii, they were transferred out to 28 different nursing homes.
This is a smart analysis, and devastating in its implications. American hospitals do a debatable job right now of handling infection control — but overwhelmingly, they are handling infection control as individual institutions, not as competitors in a local market, and certainly not as members of a geographic region. Yet this data demonstrates clearly that cooperation between hospitals and other healthcare institutions — most of which don’t have hospitals’ infection-control budgets or personnel — is going to be essential if we want to put the brakes on Acinetobacter before it soars in the civilian medical system in the same way it did in the military one.
It’s been a few days since the rollout of the White House’s proposed 2011 budget request, time enough for people to dig deep into the minutiae and figure out what that massive document really says. The Infectious Diseases Society of America has done the drilling for the health and infectious disease line items, and I’m sorry to say the news is not good.
Worst first: The proposed budget would cut funding for the CDC’s antimicrobial resistance programs by 50%, $8.6 million. That means that only 20 state or local health departments, or health care institutions, will get money from CDC for surveillance and control of resistant bugs. That’s only 40% of what was funded this year, when 48 health departments and health systems were funded. Which is very disturbing: If there’s one thing almost everyone agrees on with regard to MRSA, it’s that we need more surveillance, not less.
In addition, all state grants in the Get Smart About Antibiotics program, which runs campaigns to reduce inappropriate use, get zeroed out.
There are other cuts as well to infectious-disease program at CDC and elsewhere in HHS, including to to a major childhood immunization program and to pandemic defenses. And funding for HIV/AIDS, TB and other NIH research programs barely tiptoe upward.But these frank cuts in programs to combat antimicrobial resistance, at a time when MRSA is burgeoning, Gram negative organisms such as Acinetobacter are gaining ground, and drug development is stalling, surely cannot be smart.
The IDSA analyis is here.
From the excellent and forward-thinking research team at Extending the Cure comes a dismaying report: over 7 years, a more than 3-fold increase in resistance in the Gram-negative bacterium Acinetobacter baumanii to its drug of last resort, imipenem.
Because MRSA is a Gram-positive, we don’t talk much here about the Gram-negatives — the two categories of bacteria have different cell-wall structures and thus are treated using different categories of drugs. (That structural difference causes them to react in different ways to a stain invented by a scientist named Gram in the 19th century.) But the resistance situation with Gram-negatives is at least as dire as with MRSA, possible more so, because there are fewer new drugs for Gram-negatives in the pharmacology pipeline (as discussed in a New Yorker article by Dr. Jerome Groopman last year.)
And Acinetobacter is one nasty bug, as science journalist Steve Silberman ably documented in Wired in 2007 when he traced the spread of the organism through the military medical-evacuation chain from Iraq, demonstrating that the vast increase in resistant Acinetobacter among US forces was due to our own poor infection control.
The Extending the Cure paper (which will be published in February in Infection Control and Hospital Epidemiology) puts hard numbers to the Acinetobacter problem. Drawing on data from the private Surveillance Network, which gathers real-time electronic results from 300 US hospitals, they find:
- full resistance to imipenem rose from 4.5% of isolates in 1999 to 18.2% in 2006 — a 300% increase
- intermediate resistance rose from 1.3% of isolates to 9.4 — a 623% increase
- susceptible isolates declined from 94.1% to 72.4% — a 23% decrease.
The authors write:
Our results demonstrate substantial national and regional increases in carbapenem resistance among clinical isolates of Acinetobacter species over the period 1999–2006. Increasing carbapenem resistance among Acinetobacter species is particularly troubling, because it is very often associated with multidrug resistance and because it is occurring in the context of increases in the incidence of Acinetobacter infection.
There’s a further point to be made that is not explicit in the paper that I can see (though it is often made by Extending the Cure researchers). Acinetobacter needs attention, just as MRSA does — but if we focus just on the individual organisms, we are not going far enough. Antibiotic resistance is a system problem: It is an issue of infection control, of drug development, of agricultural organization, of federal priorities. It needs sustained attention and comprehensive, thoughtful, wide-ranging response. Now would not be too soon.