Drug-resistant bacteria brewing to become a ‘superbug’ for children

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As bacteria evolves to fight antibiotics, the most likely to suffer are children with immature immune systems.
New evidence that the power of antibiotics is fading fast has been gleaned from a decade-long study of child patients.

Scientists are in a race to develop new medicine to fight antibiotic resistant bacteria as infection rates soar. T

he Center for Disease Control and Prevention found that infections from P. aeruginosa – relatively common bacteria that can cause skin rashes and ear infections – have grown increasingly antibiotic resistant.

The bacterium isn’t harmless, as it’s been known to cause severe symptoms leading to death.

The alarming findings, which are outlined in the latest issue of the Journal of the Pediatric Infectious Diseases Society, come as the result of a decade-long survey involving child patients aged 11-17 from 300 hospitals across the United States.

It was discovered that 15.4 percent of P. aeruginosa bacteria were resistant to at least three types of antibiotics in 1999, but that number exploded to 26 percent by 2012.

Even more worrisome, the number of infections from P. aeruginosa has increased in children.

Despite P. aeruginosa being relatively commonplace, the bacteria “can be serious and are associated with significant morbidity and mortality,” author Latania K. Logan, a doctor with Rush University Medical Center, says.

Pseudomonas aeruginosa

In some cases, there is risk of prolonged illness bringing about complications that can result in death in extreme cases.

“Highly drug-resistant P. aeruginosa infections leave health care providers with limited – or sometimes no –antibiotic choices available, and these antibiotics are less safe and more toxic in children,” added author Sumanth Gandra of the Center for Disease Dynamics, Economics & Policy.

Even more troubling is that the effectiveness of carbapenems, a broad-spectrum antibiotic thought of as a last resort for antibiotic resistant bacteria, has decreased.

In 1999, only 9.4 percent of bacteria were resistant to carbapenems, but by 2012 that number had doubled to 20 percent, meaning that there is a one in five chance that the strongest antibiotic will not be effective in killing bacteria.

Antibiotic resistant bacteria have been an ongoing international concern for some time now, but the people most likely to suffer are children, who have weaker, less developed immune systems and are more susceptible to infection.

The CDC hopes that these findings inspire improved tracking of antibiotic resistant bacteria in order to improve prevention

Practice Essentials

Pseudomonas aeruginosa has become an important cause of gram-negative infection, especially in patients with compromised host defense mechanisms. It is the most common pathogen isolated from patients who have been hospitalized longer than 1 week, and it is a frequent cause of nosocomial infections. Pseudomonal infections are complicated and can be life-threatening.

Pseudomonas aeruginosa Infections

Signs and symptoms

Pseudomonal infections can involve the following parts of the body, with corresponding symptoms and signs:

  • Respiratory tract (eg, pneumonia)
  • Bloodstream (bacteremia)
  • Heart (endocarditis)
  • CNS (eg, meningitis, brain abscess)
  • Ear (eg, otitis externa and media)
  • Eye (eg, bacterial keratitis, endophthalmitis)
  • Bones and joints (eg, osteomyelitis)
  • GI tract (eg, diarrhea, enteritis, enterocolitis)
  • Urinary tract
  • Skin (eg, ecthyma gangrenosum)

Physical findings depend on the site and nature of the infection, as follows:

  • Endocarditis: Fever, murmur, and positive blood culture findings; peripheral stigmata such as Roth spots, Janeway lesions, Osler nodes, splinter hemorrhages, and splenomegaly
  • Pneumonia: Rales, rhonchi, fever, cyanosis, retractions, and hypoxia; occasionally shock; with cystic fibrosis, clubbing, increased anteroposterior (AP) diameter, and malnutrition
  • GI tract: Fever, signs of dehydration, abdominal distention, and signs of peritonitis; physical findings of Shanghai fever
  • Skin and soft tissue infections: Hemorrhagic and necrotic lesions, with surrounding erythema; subcutaneous nodules, deep abscesses, cellulitis, and fasciitis; in burns, black or violaceous discoloration or eschar
  • Skeletal infections: Local tenderness and a decreased range of motion; neurologic deficits
  • Eye infections: Lid edema, conjunctival erythema and chemosis, and severe mucopurulent discharge
  • Malignant otitis externa: Erythematous, swollen, and inflamed external auditory canal; local lymphadenopathy
  • Bacteremia: Fever, tachypnea, and tachycardia; hypotension and shock; jaundice

Treatment

Many P. aeruginosa isolates are resistant to a large range of antibiotics and may demonstrate additional resistance after unsuccessful treatment. It should usually be possible to guide treatment according to laboratory sensitivities, rather than choosing an antibiotic empirically. If antibiotics are started empirically, then every effort should be made to obtain cultures (before administering first dose of antibiotic), and the choice of antibiotic used should be reviewed when the culture results are available.

The antibiogram of P. aeruginosaon Mueller-Hinton agar

Due to widespread resistance to many common first-line antibiotics, carbapenems, polymyxins, and more recently tigecyclinewere considered to be the drugs of choice; however, resistance to these drugs has also been reported.

Despite this, they are still being used in areas where resistance has not yet been reported. Use of β-lactamase inhibitors such as sulbactam has been advised in combination with antibiotics to enhance antimicrobial action even in the presence of a certain level of resistance.

Combination therapy after rigorous antimicrobial susceptibility testing has been found to be the best course of action in the treatment of multidrug-resistant P. aeruginosa.

Some next-generation antibiotics that are reported as being active against P. aeruginosa include doripenem, ceftobiprole, and ceftaroline. However, these require more clinical trials for standardization.

Therefore, research for the discovery of new antibiotics and drugs against P. aeruginosa is very much needed. Antibiotics that may have activity against P. aeruginosa include:

  • aminoglycosides (gentamicin, amikacin, tobramycin, but not kanamycin)
  • quinolones (ciprofloxacin, levofloxacin, but not moxifloxacin)
  • cephalosporins (ceftazidime, cefepime, cefoperazone, cefpirome, ceftobiprole, but not cefuroxime, cefotaxime, or ceftriaxone)
  • antipseudomonal penicillins: carboxypenicillins (carbenicillin and ticarcillin), and ureidopenicillins (mezlocillin, azlocillin, and piperacillin). P. aeruginosa is intrinsically resistant to all other penicillins.
  • carbapenems (meropenem, imipenem, doripenem, but not ertapenem)
  • polymyxins (polymyxin B and colistin)[46]
  • monobactams (aztreonam)

As fluoroquinolone is one of the few antibiotics widely effective against P. aeruginosa, in some hospitals, its use is severely restricted to avoid the development of resistant strains. On the rare occasions where infection is superficial and limited (for example, ear infections or nail infections), topical gentamicin or colistin may be used.

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