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ANTIBIOTIC RESISTANCE - EASTERN MEDITERRANEAN
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A ProMED-mail post
<http://www.promedmail.org>;
ProMED-mail is a program of the
International Society for Infectious Diseases
<http://www.isid.org>;

Date: Tue 28 Oct 2014
Source: The Atlantic [edited]
<http://www.theatlantic.com/health/archive/2014/10/invincible-bacteria-in-the-middle-east/381671/>;


Doctors in Jordan, the region's leading destination for medical
tourism, say antibiotic-resistant infections are at an all-time high.

"We've been noticing an organism, _E. [Escherichia] coli_," [Dr.
Faris] Bakri said. "Many patients come with urinary-tract infections
with this organism," but it doesn't respond to treatment as it once
did. In 2000, _E. coli_ could be treated by the drug ceftriaxone 70 or
80 percent of the time, he estimated. Now its susceptibility is 37
percent, according to Bakri's data, which also show increasing
antibiotic resistance among other bacteria. His findings, based on the
hospital's patients, parallel national trends. "It's all over the
country. Everyone's complaining of this phenomenon," he said.

In this new nightmarish world, patients with moderate infections are
admitted to hospitals "for very expensive IV antibiotics," Bakri said,
because "they just won't respond to oral antibiotics." For virulent
infections, even fewer antibiotics are effective, and treatment is
more complex. And as health systems deteriorate in surrounding
countries, war-injured patients with complicated wounds are flocking
to Jordan, the Middle East's top destination for medical tourism, for
treatment, bringing fierce infections with them.

"We think that the Middle East is one of the hotspots globally for
antibiotic resistance," said Richard Murphy, an infectious-disease
specialist with Doctors Without Borders. We spoke in September [2014]
during a 2-day conference in Amman organized by DWB [Doctors Without
Borders] to jumpstart regional discussion and action on antibiotic
resistance. The global medical NGO works all over the world, but it
encounters notably high rates of resistance in the Middle East.
In this perfect storm of relaxed policy and lack of awareness, the
abuse of antibiotics is almost a baseline in healthcare.

In Amman, DWB runs a reconstructive surgical project, which tackles
complex cases like severe burns or bone infections. Since 2006, the
project has treated 3000 patients from places like Gaza, Yemen, Libya,
Syria, and Iraq. DWB's analysis found that drug-resistant bacteria
caused 69 percent of all infections in Syrian patients and were
present in 55 percent of Iraqi patients with bone infections. The
project's surgical coordinator, Dr. Rashid Fakhri, estimated that
overall, 60 to 65 percent of bacteria among the project's patients
carry some form of resistance.

To kill these infections, "the antibiotic we use is the last one used
in Europe," said Marc Schakal, DWB's head of mission for Jordan and
Iraq. That antibiotic is imipenem, a broad-spectrum intravenous
medication. Although it's usually a last resort, it's the drug DWB
uses most frequently in Amman because 1st-line antibiotics aren't as
effective. A full 6-week course of imipenem costs USD 2600 to USD
3000.

>From 1970 to 1995, Arab countries went through "an impressive
construction program of public hospitals and health centers,"
according to a 2012 review of the area's health services. Healthcare
became more readily available in many of these countries, except ones
in conflict, and several, including Jordan, "developed world-class
factories for the manufacture of generic medications" for export and
domestic use. The report highlighted "the inappropriate usage of
antibiotics," which, The Lancet has written, "has contributed to the
development of microbial resistance in the region." As health systems
and access to medical drugs flourished, however, awareness about their
proper use among both health professionals and patients lagged.

"People here take antibiotics for knee pain, for runny noses," Bakri
said. "Doctors are under a lot of pressure from the patient to
prescribe antibiotics, because if the patient doesn't receive
antibiotics, he will not go back to the doctor." Dr. Najwa Jarour,
head of the infection-control department at Jordan's Ministry of
Health, added, "Even doctors write prescriptions for antibiotics
without knowing if [an infection] is viral or bacterial," and patients
often don't complete prescribed courses of antibiotics, stopping as
soon as they feel better.

Even without a prescription, a person can walk into a pharmacy in
Jordan, present symptoms or a self-diagnosis -- "Good afternoon, I
believe I have a urinary-tract infection" -- and the pharmacist will
most likely hand over some affordable blister packs of antibiotics. In
this perfect storm of relaxed policy, lack of awareness, and doctors
and pharmacists worried about making money, the lax dispensation of
antibiotics and their consequent abuse is almost a baseline in
healthcare.

The other major factor is war. Recent years have witnessed substantial
violence in the Middle East -- 2014 alone includes the ongoing war in
Syria, renewed fighting (again) in Iraq, and Israel's war with Hamas,
plus continuing conflicts in Yemen, Libya, and elsewhere. Better
initial treatment is not always feasible in conflict zones. In Syria,
60 percent of hospitals have been damaged or destroyed since the start
of the war.

"When health systems are fragile and patients don't get good initial
treatment for their injuries, they frequently end up living with a
chronic injury," DWB's Murphy explained. These injuries are
susceptible to infection, which could be avoided if better initial
treatment were available, he said. DWB's Iraqi patients in Amman have
undergone an average of 4 previous operations, with 19 months on
average between injury and DWB admission.

Even with ... Bakri's internal data, and DWB's analysis of patients
bearing extraordinarily complex wounds, it's hard to glean precisely
the impact on Jordan from antibiotic resistance. "You've got no idea
of the levels of resistance coming in," said Tim Walsh, a medical
microbiology and antimicrobial resistance professor at Cardiff
University in Wales, while in Jordan, data on resistance are "almost
nonexistent." Indeed, Ministry of Health surveillance of resistance is
limited to select units in 4 public hospitals, though it has revealed
high levels of bacterial resistance to both 1st-line and last-resort
antibiotics.

Bakri said the university hospital had not conducted cost-impact
studies, while Jarour, the health ministry official, couldn't say what
antibiotic resistance might cost Jordan in the long run. But both were
certain they'd see higher healthcare costs, worsening morbidity rates,
and above all, more deaths. As Bakri stated frankly, "It's going to be
a disaster."

[Byline: Elizabeth Whitman]

--
Communicated by:
ProMED-mail from HealthMap Alerts
<[e-mail]>

[Antimicrobial resistance is a worldwide problem, affects many types
of pathogens, has appeared in both healthcare and more recently in
community-acquired infections, and has major clinical and economic
consequences. A recent report by WHO revealed "extensive antibiotic
resistance across the WHO Eastern Mediterranean Region", which
includes the countries mentioned in the article above (Jordan, Syria,
Iraq, and Lybia)
(<http://www.who.int/mediacentre/news/releases/2014/amr-report/en/>;
and ProMED-mail post Antibiotic resistance - worldwide: WHO
20140501.2442194).

Similar to the article above, the WHO report goes on to say that in
the WHO Eastern Mediterranean Region, "In particular, there are high
levels of _E. coli_ resistance to 3rd generation cephalosporins and
fluoroquinolones -- 2 important and commonly used types of
antibacterial medicine. Resistance to 3rd generation cephalosporins in
_K[lebsiella] pneumoniae_ is also high and widespread.... The report
reveals major gaps in tracking of antibiotic resistance in the
Region."

Most likely the article above is referring to extended-spectrum
beta-lactamase (ESBL)-producing _E. coli_. ESBLs hydrolyze penicillins
and cephalosporins, including the extended-spectrum cephalosporins
with an oxyimino side chain (cefotaxime, ceftriaxone, ceftazidime, and
cefepime), as well as the oxyimino-monobactam aztreonam. Most ESBLs
are inhibited to some extent by beta-lactamase inhibitors such as
clavulanate, sulbactam, or tazobactam in vitro; but the clinical
effectiveness of beta-lactam/beta-lactamase inhibitor combinations
cannot be relied on consistently for therapy.

Because the genes that encode ESBLs are located on plasmids, the
ESBL-encoding genes are easily transferable to other bacteria of the
same or even different species. These plasmids also carry genes
conferring resistance to several non-beta-lactam antibiotics.
Consequently, ESBL-producing isolates are commonly resistant to many
classes of antibiotics, most frequently aminoglycosides,
fluoroquinolones, tetracyclines, chloramphenicol, and
sulfamethoxazole-trimethoprim. Infections caused by these multiple
drug-resistant organisms are most reliably treated with a carbapenem
antibiotic, such as imipenem, meropenem, ertapenem, and doripenem.

There are multiple types of ESBLs, such as, TEM, SHV, CTX-M, OXA, each
with multiple subtypes. One type, CTX-M-15 is currently the most
widespread type in _E. coli_ in the UK and is reported to be widely
prevalent in the community (Woodford N, Ward ME, Kaufmann ME, et al:
Community and hospital spread of _Escherichia coli_ producing CTX-M
extended-spectrum beta-lactamases in the UK. J Antimicrob Chemother
2004; 54(4): 735-43. Available at
<http://jac.oxfordjournals.org/content/54/4/735.full>;.)

The use of carbapenems, the antibiotics of last resort to treat
multidrug-resistant Enterobacteriaceae, has now become compromised by
the spread of carbapenemases (e.g., KPCs and NDMs), beta-lactamases
that destroy the carbapenem antibiotics, which leaves only toxic or
otherwise suboptimal antibiotics to treat patients infected by
carbapenemase-producing Enterobacteriaceae.

A map showing the countries in the WHO Middle Eastern Region is
available at: <http://www.who.int/about/regions/emro/en/>;. - Mod.ML]

[See Also:
Gram-negative bacilli, MDR - Uruguay: (FD) KPC, nosocomial, fatal
20140928.2812844
NDM-4 carrying Enterobacteriaceae - India: (UP) hospital sewage
20140905.2749919
Enterobacteriaceae, carbapenem resistant - USA: southeastern community
hospitals 20140719.2621485
Antibiotic resistance - new metallo-beta-lactamase (NDM-1) inhibitor
20140627.2568937
Antibiotic resistance - India 20140505.2449567
Antibiotic resistance - worldwide: WHO 20140501.2442194
NDM-1 carrying Enterobacteriaceae - China: (HK) 20140501.2442036
Enterobacteriaceae, carbapenem resistant - France: ex India
20140412.2399151
NDM carrying Gram-negative bacilli - Americas: Update
20140309.2322398
Enterobacteriaceae, carbapenem resistant - UK: (England) increased
incidence 20140308.2321781
NDM-1 carrying E. coli - USA: (IL) ERCP 20140104.2151607
2013
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Antimicrobial resistance - Netherlands ex Egypt: family
2011
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Antibiotic resistance, E. coli - UK (02): (Wales) ESBL 20111128.3471
Antibiotic resistance, E. coli - UK: (Wales) ESBL 20111126.3454
2007
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E. coli, ESBL - UK 2000