Rapid Antibiotic Testing Comes of Age


Phoenix—In recent years, there has been an explosion of FDA-approved rapid diagnostic testing methodologies for infectious diseases. During an education session at the 2017 annual meeting of the American College of Clinical Pharmacy, pharmacists discussed some of the excitement surrounding the recent advances in treating the most worrisome bugs.

“Rapid diagnostic tests represents one of the few bright spots in the changing world of escalating antimicrobial resistance and stewardship,” said Katherine Perez, PharmD, BCPS-AQ ID, an infectious disease clinical specialist at Houston Methodist.

Dr. Perez pointed out that rapid identification of microorganisms and resistance is critical for targeted treatment in serious infections caused by multidrug-resistant gram-negative bacteria (GNB). Research efforts have focused on pathogens associated with increased morbidity, mortality and excessive health care costs, including influenza virus, methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus species, Clostridium difficile, extended-spectrum beta-lactamase (ESBL)-producing Klebsiella species, carbapenemases, Mycobacterium tuberculosis and Candida species.


Current conventional culture-based methods to isolate and identify a pathogen, followed by susceptibility testing, can take 72 hours or more. This is concerning, Dr. Perez noted, because delaying administration of appropriate antimicrobials is associated with increased mortality rates for patients with gram-negative septicemia and septic shock (Clin Infect Dis 2013;57:S139-S170). Having the ability to detect the presence of resistant bacteria in a clinical sample in less than one hour, Dr. Perez noted, helps improve the effectiveness of antimicrobial stewardship programs.

In an ideal world, antimicrobial treatment would be prompt; appropriate; administered at an adequate dose and interval, guided by pharmacokinetic/pharmacodynamic principles; and discontinued appropriately, based on clinical response and microbiological data. All of this, Dr. Perez noted, is contingent on accurately determining a pathogen’s identification and antimicrobial susceptibility.

Various Methodologies

Emerging rapid detection methods of pathogens include a variety of technologies that vary greatly in complexity, price, speed and ability to identify single or multiple pathogens. Dr. Perez highlighted a number of rapid infectious disease diagnostics using different methodologies, including the polymerase chain reaction (PCR)-based FilmArray Blood Culture Identification panel (BioFire Diagnostics LLC). The panel tests for 24 pathogens and three antibiotic resistance genes associated with bloodstream infections. The test can accurately identify pathogens in more than nine of 10 positive blood cultures in about an hour, with only two minutes of hands-on time, she said (J Clin Microbiol 2016;54:687-698).


The advantages of PCR-based testing, she noted, include rapid results, low detection limits, specific organism detection and subtyping, not requiring growth on media, high throughput and, generally, short hands-on time for laboratory staff. Disadvantages include susceptibility to contamination, the need for dedicated laboratory space for instruments, and dependence on quality of products used, and most require initiation from positive cultures/single colonies. PCR cannot indicate viability of the pathogen detected and comes with practical limitations that can affect turnaround time.

Targeting Worrisome Bugs

Ryan Shields, PharmD, MS, associate professor of medicine in the Division of Infectious Diseases at the University of Pittsburgh, said carbapenem-resistant bugs top the list of most worrisome bugs. Carbapenem-resistant Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacteriaceae (CRE) are listed as critical priorities for research and development of new antibiotics by the World Health Organization. The CDC lists multidrug-resistant A. baumannii and P. aeruginosa as serious threats, and CRE as an urgent threat.


Carbapenem-resistant pathogens, Dr. Shields said, are associated with loss of our last line of defense against resistant pathogens and cross-resistance to other antibiotic classes. They are also associated with increased lengths of stay, health care expenditures and increased mortality rates among patients. “Carbapenem resistance is a major threat to public health,” he said.

A recent study concluded that antibiotic stewardship and infection prevention and control have been unable to prevent the rapid spread of resistant GNB, particularly carbapenem-resistant P. aeruginosa and other nonfermenting GNB, ESBL-producing and CRE (Intensive Care Med 2017 Jul 21. [Epub ahead of print]). Carbapenem-resistant Klebsiella pneumoniae, Dr. Perez said, is an emerging nosocomial pathogen associated with considerable mortality.

Rapid tests should detect all carbapenem-resistant organisms and distinguish carbapenemase-producing organisms from isolates that are resistant to carbapenems because of other mechanisms, Dr. Perez noted. The organisms have diverse enzyme types and considerable variation in levels of phenotypic carbapenem resistance (e.g., minimum inhibitory concentration evaluation). Non–carbapenemase-mediated carbapenem resistance complicates things.

The Rapidec Carba NP biochemical test (bioMérieux) detects any type of carbapenemase activity by monitoring the color change of a pH indicator according to hydrolysis of the substrate, imipenem. The tests are rapid, easy to read and handle, and cost-effective, and have a turnaround time of approximately one hour. They can be used for first-line screening in the absence of molecular typing, Dr. Perez said.

Table. Integrating Rapid Diagnostics Into Practice
Beta-Lactamase Bacteria Recommended Therapy
CTX-M (ESBL) Enterobacteriaceae Ertapenem (Invanz, Merck)
KPC Klebsiella pneumoniae and other enteric gram-negative organisms Colistin + tigecycline/aminoglycoside/carbapenem; ceftazidime-avibactam (Avycaz, Allergan)
NDM carbapenemases K. pneumoniae and other enteric gram-negative organisms Colistin + tigecycline; aztreonam (Azactam, Bristol-Myers Squibb) + ceftazidime-avibactam
VIM or IMP carbapenemase Pseudomonas aeruginosa Colistin + aztreonam/aminoglycoside/tigecycline
OXA beta-lactamases P. aeruginosa Colistin + high-dose carbapenem
Acinetobacter baumannii Colistin + minocycline; high-dose carbapenem
ESBL, extended-spectrum beta-lactamase Source: Katherine Perez, PharmD, BCPS-AQ ID.

Integrating Into Practice

Dr. Perez noted that the Infectious Diseases Society of America, CDC and National Quality Forum have recognized the emerging role of rapid diagnostics and biomarkers in antimicrobial stewardship programs. Molecular biology and testing can be used to improve antimicrobial stewardship interventions, assist in anti-infective escalation and de-escalation efforts, and improve clinical outcomes.

Implementation of rapid diagnostic tests may be cost-neutral or even constitute a cost savings when stewardship efforts streamline care. “Rapid diagnostic tests can reduce total hospital costs by decreasing length of stay,” Dr. Perez said.

Multiple stakeholders, including infectious disease physicians, microbiologists and laboratory pharmacists, need to create guidance for clinicians up front regarding the use of rapid infectious disease diagnostics, Dr. Perez noted. “There is a need to connect the dots among antimicrobial stewardship, rapid diagnostics and improved outcomes to make this case,” she said. “Who gets notified when an organism and a resistance marker are identified by rapid diagnostics?”

Providing Guidance

Stewardship pharmacists can provide guidance to clinicians to positively affect patient care. Some stewardship programs use automated alerts for positive blood cultures coupled with antimicrobial stewardship interventions, to ensure that a patient is prescribed effective antibiotics sooner, Dr. Perez said. Selective antibiogram reports for blood culture isolates are helpful for driving empirical choices and may be useful particularly for multidrug-resistant organisms.

“Advances in testing provide new opportunities for stewardship programs to streamline care for patients with serious infections,” she added. “Rapid diagnostic tests are game-changing for patient care moving forward.”

Are men unfairly castigated for having “man flu” and running to their sick beds at the merest sign of a sniffle?

Man sneezing on a busHe will be in bed soon with a damp towel on his brow…

Research suggests that women are at greater risk of getting flu than men because they tend to spend more time around children, who are more likely to have a flu-like illness in the first place.

A nationwide flu survey carried out by London School of Hygiene and Tropical Medicine during last winter found that women were 16% more likely to say they had flu symptoms.

So is it really women who are making all the fuss about being unwell?

This winter, the online flu survey is up and running again and aiming to find out the answer.


The survey needs people of all ages around the country to report any flu-like symptoms by filling in an online questionnaire.

This data will be used to map the spread of flu across the country during the winter.

Researchers can then analyse how the virus spreads and who it affects.

How ill?

Dr Alma Adler, who runs the project, says they wanted to find out more about gender differences and flu in this year’s survey.

“We haven’t found any evidence of ‘man flu’ yet.

“The biggest risk factor is having children under the age of 18 and for this reason women are more at risk of flu.

“This year we have included some new questions, such as ‘How bad do you feel?’

“People can answer on a number scale of one to 10.”

What is flu?

How an influenza virus particle might look
  • Flu is a respiratory illness linked to infection by the influenza virus.
  • Symptoms usually include headache, fever, cough, sore throat, aching muscles and joints.
  • Influenza occurs most often in winter and usually peaks between December and March.
  • The virus was first identified in 1933.
  • There are two main types that cause infection: influenza A and influenza B
  • New strains of the virus are constantly emerging, which is why the flu vaccine should be given each year.

This is the crucial part, asking people how they feel when they have flu, by delving into the psychology of illness – not just the science.

‘More sensitive’

And that could help scientists discover if men and women experience flu differently.

John Oxford, professor of virology at Queen Mary, University of London, says there is no scientific evidence for “man flu” but there is a difference in behaviour.

“We know that women react differently to infection. They are more sensitive to their health. Men bluster around a bit.

“So there are differences in how men and women perceive illness and then differences in behaviour.

“Men think they are going to die when they are unwell, so they go to bed and expect women to look after them.”

Dr Douglas Fleming, from the Royal College of GPs’ flu research unit, says there is no rule when it comes to how flu viruses affect people.

“Every flu virus is different. It depends on the strain. We don’t know ahead of time how it will affect people.

“Different viruses affect men, women and children differently.”

Weaker sex

Previous research from the University of Cambridge came to a different conclusion.

It found evidence that women were better at fighting infections than men.

Man getting the seasonal flu jabThe over-65s are among those entitled to a free flu jab

Evolutionary factors and hormonal differences were thought to make males more susceptible to infection than females.

In the animal world too, across a range of species, males tend to be the “weaker sex” in terms of immune defences, the Cambridge research team said.

This would back up the argument that “man flu” exists because men would be more susceptible to viruses and therefore more likely to be unwell.

But if children are the main sufferers and harbourers of influenza, spreading it to their parents and grandparents, then won’t mothers automatically be in the firing line?

Prof Oxford says men will still be infected just as much.

“If the parents are sleeping together in the same bed, spending at least eight hours in the same room sharing pillows, then the flu virus will soon move on to the husband.”


The Health Protection Agency (HPA) started its weekly monitoring of flu activity in the UK population in October.

So far this winter, the number of people with flu symptoms going to see their GP is low (6.9 per 100,000 in England).

This could explain why just 65% of those aged over 65 and 32% of pregnant women have taken up the offer of a flu vaccine.

Dr Richard Pebody, head of seasonal flu surveillance at the HPA, said they are hoping this winter will mirror last winter’s trend.

“The 2011/2012 flu season was one of the lowest on record – following two years of high flu activity, including the 2009 flu pandemic. This demonstrates how unpredictable the flu season can be.”

Whether you are a man or a woman, there is a chance you could be infected by the flu virus in the coming months.

If you are in any of the “at risk” groups, the key is to be protected in advance by getting the flu jab.

Then keep a box of tissues and a hot water bottle handy.