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SUPERBUG KPC-Oxa 48 WOULD NOT BE TAMED WITH ANY KNOWN ANTIBIOTIC & BRIAN POOL DIED

SUPERBUG THAT DEFIES ALL TREATMENTS WITH EVERY ANTIBIOTIC KNOWN

Brian Pool caught a superbug while overseas.

He died fighting a superbug that no antibiotic in the world could touch.

Wellington teacher Brian Pool is believed to be New Zealand’s first victim of an aggressive superbug, caught while he was overseas, that is resistant to every type of antibiotic.

Mr Pool, 68, spent most of the last six months of his life in quarantine, unable to leave his room even to sit in the courtyard.

“It was sad because we couldn’t give him a hug, we couldn’t really kiss him,” twin sister Maureen Dunn said.

“He just wanted to get out in the sun, and we couldn’t take him out.

“Being his twin sister, I would be the one who always rescued him . . . it was terrible, but there was nothing we could do.”

Her brother died on July 6, from complications caused by a stroke and unrelated to the bug.

But doctors say his immune system was weakened by fighting the nightmare bacteria.

The adventurous teacher, known for his quirky sense of humour, was living in Vietnam and teaching English when he suffered a brain haemorrhage on January 6.

He had surgery in Vietnam, where part of his skull was removed to relieve pressure on his brain, and was flown to New Zealand.

In Wellington Hospital, he was immediately isolated, a standard precaution for overseas patients.

Tests revealed he was carrying a strain of bacterium known as KPC-Oxa 48 – a “pan-resistant” organism that repels every kind of antibiotic.

“Nothing would touch it. Absolutely nothing,” Wellington Hospital clinical microbiologist Mark Jones said yesterday.

“It’s the first one that we’ve ever seen that is resistant to every single antibiotic known.

“This man was in the post-antibiotic era, and this is why so many agencies over the world are raising alarm bells.”

Earlier this year, British chief medical officer Sally Davies described resistance to antibiotics as a “catastrophic global threat” that should be ranked alongside terrorism.

New Zealand hospitals are already seeing increasing cases of multi-resistant “superbugs”, which can be treated by only a limited number of expensive antibiotics.

Dunn said the family was frightened, and even Mr Pool’s doctors did not seem to know what the superbug might do.

“They were shit scared, to put it bluntly, in case these bugs were transferred to another patient or taken out into the community.”

The message to others was clear, she said: “Don’t have an operation in a hospital overseas.”

Wellington Hospital infectious disease physician Michelle Balm said Mr Pool’s superbug could have been contracted when he was in hospital in Vietnam, or a few years earlier when he had hernia surgery in India.

Fairfax NZ News

WHAT IS KPC-Oxa 48 ?? See below

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To the Editor: Class D OXA β-lactamases are characterized as penicillinases that can hydrolyze oxacillin and cloxacillin and are poorly inhibited by clavulanic acid and EDTA. OXA-48 is one of the few members of this family to possess notable carbapenem-hydrolyzing activity (1). First described in 2004 in Turkey, OXA-48 has recently started to spread in Europe and the Middle East (2). We report the recent emergence of the plasmid-encoded blaOXA-48 gene in multidrug-resistant Enterobacteriaceae recovered from patients in Dakar, Senegal, in hospitals and in the community.

From November 2008 through October 2009, 11 Enterobacteriaceae isolates (8 Klebsiella pneumoniae, 1 Escherichia coli, 1 Enterobacter cloacae, and 1 Enterobacter sakazakii) with reduced susceptibility to imipenem were identified at the Institut Pasteur (Dakar, Senegal). Antibacterial drug susceptibility was determined by the disk diffusion method and interpreted according to the European Committee on Antimicrobial Susceptibility Testing guidelines (www.eucast.orgExternal Web Site Icon). Nine isolates were resistant to expanded-spectrum cephalosporins and also to other antibacterial drug classes.

The isolates were recovered from 6 patients with urinary tract infections, 4 patients with surgical infections, and 1 patient with omphalitis. Nine infections were hospital acquired (Le Dantec and Principal Hospitals). Because the patients died before antibacterial drug susceptibility testing could be completed, all 5 patients with surgical infections or omphalitis received only empirical therapy with amoxicillin/clavulanate. One patient with a nosocomial urinary tract infection caused by a co-trimoxazole–susceptible strain was successfully treated with this antibacterial agent. The antibacterial drug regimens of the remaining 4 patients were not known, and they were lost to follow-up. We determined the MICs of imipenem, meropenem, and ertapenem by using the Etest method (AB Biodisk, Solna, Sweden), which showed that 9 isolates were susceptible to imipenem and meropenem but either intermediately susceptible or resistant to ertapenem (Table). The 2 imipenem-nonsusceptible isolates were susceptible or intermediately susceptible to meropenem, and both were resistant to ertapenem.

We used previously described PCRs (1,37) to screen for carbapenem-hydrolyzing β-lactamase genes (blaVIM, blaIMP, blaKPC, and blaOXA-48), as well as plasmid-encoded blaCTX-M, blaAmpC, blaOXA-1, and blaTEM β-lactamase genes; the aac(6′)-Ib aminoglycoside resistance gene; the quinolone resistance genes qnrA,B,S; the tetracycline resistance genes tetA,B,D; and class 1 integron. The blaOXA-48, blaCTX-M, blaAmpC, and aac(6′)-Ib genes and the variable region of class 1 integron were then characterized by direct DNA sequencing of the PCR products. blaOXA-48 was present in all 11 isolates. blaVIM, blaIMP, and blaKPC were not detected. The qnr genes were present in 7 isolates resistant to ciprofloxacin. The aac(6′)-Ib-cr variant was present in 7 isolates resistant to gentamicin, tobramycin, and ciprofloxacin.

The 9 isolates resistant to expanded-spectrum cephalosporins all harbored the blaCTX-M-15 gene. The E. coli isolate also harbored the plasmid-encoded blaAmpC gene ACT-1; blaCTX-M-15, blaOXA-1, blaTEM, and aac(6′)lb-cr were associated in 6 isolates. Long-range PCRs showed that these latter 4 genes were located in the same “multidrug resistance region,” as described in Senegal (6). Positive conjugation experiments with sodium azide–resistant E. coli J53 showed through PCR results, plasmid DNA extraction, and antibiogram patterns of the obtained transconjugants that blaOXA-48 was located on a 70-kb self-conjugative plasmid.

The genetic environment of blaOXA-48 was then investigated by PCR with primers specific for insertion sequence IS1999 and for the 5′ part of blaOXA-48 (1). blaOXA-48 was found to be part of a Tn1999 composite transposon composed of 2 copies of the insertion sequence IS1999, as reported (2). Further sequencing of the IS1999 located upstream of blaOXA-48 showed that it was consistently truncated by the insertion sequence IS1R, as initially described in Turkey and more recently in Lebanon and Egypt (2,8).

XbaI pulsed-field gel electrophoresis was then used to study the genetic relatedness of the 8 K. pneumoniae isolates. Three isolates had similar restriction profiles and had been recovered from 3 patients concurrently hospitalized at Le Dantec Hospital, suggesting nosocomial transmission. A class 1 integron harboring the dfrA1 trimethoprim-resistance gene was detected in the 3 clonal isolates.

Together, these findings show the recent emergence of blaOXA-48 in Senegal in community and hospital settings. They may also suggest the spread of the same major carrying plasmid between the Middle East and Africa. Although 9 of the 11 isolates were found to be susceptible to imipenem on the basis of their MICs, their MICs were nonetheless higher than those of blaOXA-48–negative isolates. This raises 2 issues. First, these strains might go undetected during routine antibacterial drug susceptibility testing, a problem that could be overcome by using ertapenem, a compound more susceptible to carbapenemases. Second, the clinical efficacy of imipenem on such strains is uncertain. The frequency of acquired carbapenemases, which emerged early after imipenem introduction in Senegal (2008), is probably strongly underestimated, partly owing to the limited availability of reliable clinical laboratories (9). Because multidrug resistance is prevalent among Enterobacteriaceae isolated in Dakar hospitals (B. Garin, unpub. data) and in rural communities (6), the emergence of blaOXA-48 is a clear cause for concern.

Olivier MoquetComments to Author , Coralie Bouchiat, Alfred Kinana, Abdoulaye Seck, Omar Arouna, Raymond Bercion, Sebastien Breurec, and Benoit Garin
Author affiliations: Author affiliations: Institut Pasteur, Dakar, Senegal (O. Moquet, C. Bouchiat, A. Kinana, A. Seck, S. Breurec, B. Garin); Hopital Principal, Dakar (O. Arouna, R. Bercion)

References

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  2. Carrër A, Poirel L, Yilmaz M, Akan OA, Feriha C, Cuzon G, Emerging spread of OXA-48-encoding plasmid from Turkey and beyond. Antimicrob Agents Chemother. 2010;54:136973. DOIExternal Web Site IconPubMedExternal Web Site Icon
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  7. Guessennd N, Bremont S, Gbonon V, Kacou-Ndouba A, Ekaza E, Lambert T, Qnr-type quinolone resistance in extended-spectrum beta-lactamase producing enterobacteria in Abidjan, Ivory Coast [in French]. Pathol Biol (Paris). 2008;56:43946. DOIExternal Web Site IconPubMedExternal Web Site Icon
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