The R-word: What happens when the clock winds down on new drug development?

Why are some top-notch scientists – “bioprospectors” – leaving the lab and scouring such places as the ocean floor, the Amazon rainforest and the caves of Western Canada? “I would like to look at bacteria that live in a very rare and extreme habitat and would like to see whether these types of bacteria could be our new drugs,” says the scientist in the video below.

She explains: “We now have a crisis, an antibiotic resistance crisis [on] our hands. Bacteria basically became resistant or became harder to kill.… If you don’t have new drugs people can just have these unnecessary death[s] from infection that used to be treatable before.”

Her remarks are timely. Last week the World Health Organization issued a report saying there are not enough new antibiotics in the pipeline and that most of the drugs currently in the clinical pipeline are modifications of existing classes of antibiotics and thus are only short-term solutions.

But there’s another problem. It takes decades of research and up to a billion dollars to create just one new antibiotic. Bioprospecting in such places as the caves of British Columbia is just the beginning of that process.

So what happens if we don’t beat the clock? We ration antibiotics – which has already begun in the UK – and that ain’t gonna be pretty.


Working out with millions of your little friends


Those exercise mats at your gym everyone uses aren’t quite as innocent as they look. With people pouring sweat into them all day the combination of heat and moisture creates the perfect breeding ground for bad bacteria, viruses, and fungus that give rise to such things as MRSA infections, scaly circular rashes, boils and blisters, and nail fungus.

That’s because “We are walking microbial planets [who] shed huge amounts of skin cells every day from our bodies, as many as 500 million by some estimates,” says infectious disease specialist Brad Spellberg, MD, chief medical officer at the Los Angeles County-University of Southern California Medical Center. And so “If someone has a nasty bug and they shed it, you can acquire it when you touch the surface [of the mat].”

Because even a slight cut or abrasion on your skin can give these microbes a way into your body you want to protect yourself in the following ways:

  • Bring your own mat. Clean it with soap & water or an alcohol-based sanitizer after each use.
  • Shower immediately after exercise. Don’t share items that touch your bare skin.
  • Cover any irritated or open skin – cuts and scrapes – with a bandage. Lay a towel down when you sit on shared surfaces.
  • Wash your workout clothes after each use.

Community Service: Your vaccination protects more than just you

Your vaccination will prevent you from getting sick from the diseases you inoculate against. Less well known is that it will also prevent others from getting sick. An interesting report in the online medical journal STAT tells us that this protection of others happens through something called herd immunity and, separately, by indirectly decreasing the number of those nasty “superbugs” we create, thereby lessening the number of drug-resistant infections they cause.

Herd immunity, also called community immunity, is the idea that if you immunize enough people in a given population, then even those who aren’t vaccinated are less likely to get sick. That’s because they’re less likely to come into contact with someone who is infected – because they’ve been immunized. The following chart nicely illustrates this. Notice that the more people who are immunized the better it works.


Herd Imm.


Also, if we want to get rid of superbugs then we need to stop doing what creates them – overusing and misusing antibiotics: Nobody wants to die including bugs, so as we needlessly and relentlessly assault them with antibiotics they fight back by evolving mechanisms, “body armor” if you will, that renders these indispensable drugs obsolete.

Fortunately, immunization can help remedy this chronic overuse problem in 3 ways:

First, there are vaccines for bacterial diseases such as pneumococcal infections, bacterial meningitis, or pneumonia. Thus, through immunization that prevents these bacterial infections from arising in the first place, you eliminate the need to use antibiotics.

Second, by preventing influenza and other viral infections through immunization you eliminate the need for antibiotics to treat secondary bacterial infections that often follow virus-caused respiratory illnesses.

Finally, immunization “immunizes” us from our own folly. Antibiotics only work against bacteria, not viruses. Yet we insist on using antibiotics on viral-based flu-like conditions in about 80% of those cases – a harmful, huge, and needless waste of a precious resource. Thus, if we vaccinate against these viral diseases in the first place, there will be no viral infections to (mis)treat with an antibiotic.


A 9 ½ -year old girl under clinical guidance stopped her HIV therapy 8 ½ years ago and is doing just fine: Are we onto something or is this just a one-off?




Very few people can control HIV for more than a few weeks without antiretroviral (ARV) drugs. But a 9 ½ -year-old girl in South Africa has been doing it for over 8 ½ years now, according to a case presentation this week at the International AIDS Society Conference in Paris, as reported in the journal Science.

The girl (her name is being withheld) was born to an HIV-infected mother and was given ARVs starting at 8 weeks old. The treatment was stopped at 40 weeks as part of a clinical trial and today, remarkably, she’s doing just fine. Although there is a caveat – the virus remains in her system but the level is so low it’s invisible with standard tests, detectable only by an ultrasensitive DNA sequencing method.

Researchers believe the key to the girl’s sustained remission was starting her ARV treatment shortly after she become infected – 8 weeks later. The trick, they say, is to strike the right balance between using drugs early to keep the HIV load small, yet large enough for the immune system to see enough HIV to develop a robust memory response for when the virus comes back.

More good news: This same approach has been successful – so far – in an ongoing study at the Pasteur Institute in Paris. They’re following 23 patients who started ARV treatment shortly after becoming infected. The average treatment length was 3 years. And 7 years post-treatment (on average because people entered the study at different times) the virus remains undetected in all 23. One person in the group has gone without treatment for nearly 17 years.

But these are early days for this approach and as a recent Oxford University early-treatment study reminds us, getting it right isn’t easy: the virus remained undetectable in 14% of the people in one cohort (the longer treatment group), and just 4% in the other.

And as Sharon Lewin, director of the Peter Doherty Institute for Infection and Immunity in Melbourne, Australia, observes with respect to the girl in South Africa: “Single-case reports have limited value now. … We know it happens and we need to understand why.”

Nevertheless, Mark Cotton, PhD, one of the South African researchers says, “It’s exciting that we’ve identified the child, as it could provide answers for the future.” But he cautions, “There’s a long way to go.”





When a sinus infection goes wrong it can threaten your vision and your life

Sinus infection 2


As we reported last month, antibiotics are not necessary in the vast majority of sinusitis cases because (1) sinusitis is usually viral-driven and antibiotics don’t affect viruses, and (2) even if it is a bacterial infection, it typically clears up on its own.

But not always. There’s a rare case in which a sinus infection will cause a swollen eye and this will be a sign of an opthalmic emergency because it can quickly threaten your vision or even your life. The condition is called orbital cellulitis – swelling of a membrane in front of the eye.

It starts out as a typical viral sinus infection with nasal congestion and sinus pain. But in this case, pathogenic bacteria that are normally cleared by microscopic hairs get trapped by the buildup of gunk in the sinus. Where they multiply then invade and infect the eye, the sinus cavity’s next-door neighbor.

Here’s a clinical presentation of the condition by Maya Adams, MD, of the Stanford Medical School. The following is a partial transcript taken from her online course on infectious disease at Stanford called “Stories of Infection” (see Week 3, Bacterial Infections Part 2, Orbital Cellulitis).


Today we’re going to be talking about a rare case in which a common pediatric complaint, a swollen eye, is a sign of an opthalmic emergency requiring hospitalization and immediate medical attention. This seven year old girl named Irena was brought to the urgent care clinic by her mother …

Irena’s mother tells you that her daughter has been complaining of a headache just behind her forehead. She’s also had a very stuffy nose and pain in her face that gets worse when she bends forward to tie her shoelaces …

[I]t will be important to consider orbital cellulitis as a possible cause of her symptoms. Although this is … rare … in children, it’s important to rule it out because it’s an opthalmic emergency that can quickly threaten the patient’s vision or even her life …

In Irena’s case, her sinus infection allowed bacteria a back door entry into the normally protected orbital space. The orbit [eye socket] is separated from the air filled nasal sinuses only by the thin, bony structures of the skull. Irena’s mother was probably correct that her initial symptoms of nasal congestion and sinus pain were caused by a viral infection. Irena’s immune system detected the virus and attempted to deploy alternate immune pathways to eliminate it. But this led to inflammation and blockage of the normal sinus drainage pathways. The decreased mucociliary clearance that resulted meant that an important physical barrier which usually protects the host, by preventing pathogen entry, was less effective. And bacteria were able to colonize the sinuses …

Rarely in children with bacterial sinusitis, the bacteria go on to invade through the paper thin bones separating the sinuses from the orbit. This is how they were able to enter Irena’s orbit then persist and replicate there to cause her symptoms. Once the bacteria have spread into the orbit, they can cause serious complications …

Severe edema or abscess formation can also put pressure on the optic nerve or the central retinal artery, causing loss of vision …

Because of Irena’s symptoms and her history of a recent sinus infection, the attending physician in this case decides that she should be admitted to hospital …

Luckily, no abscesses are seen, so it’s unlikely that surgical intervention will be necessary. Almost immediately after arriving at the hospital, Irena is started on two IV antibiotics, a third-generation cephalosporin, and vancomycin …

After three days on IV antibiotics, Irena’s pain and swelling are much improved and her white blood cell count normalizes. On day five, she goes home on oral antibiotics to complete a three week course of treatment. … And after ten days, Irena returns to school and her mother is able to return to work.


One more thing. Some bacteria are resistant to cephalosporin’s and “vancomycin resistance is becoming an increasingly common problem.” What would happen to Irena if one or both her antibiotics failed to work?

The “big, big, big mistakes” we make in drug therapy with sick infants


neonatal 1


The big news in medicine today is the announcement of a promising new gene-based therapy for certain leukemia patients – children and young adults aged 3 to 25 – who were facing death because every other treatment had failed: 52 of 63 patients who received the therapy last year went into remission – “a high rate for such a severe disease.”

The reports come on the heels of yesterday’s Food & Drug Administration hearing aimed at carefully assessing how safe and effective the therapy is. The FDA advisory committee wasn’t concerned about effectiveness; instead, they zeroed-in on reports of the side-effects – raging fever, crashing blood pressure, lung congestion, infertility, and the possibility of causing secondary cancers. After hearing the evidence the committee unanimously recommended that the FDA approve the drug. The agency will announce their decision in October.

And that’s how drug approval is done – except for, of all people, neonates: premature and full-term infants less than 28 days old – babies so tiny, their little hands can’t wrap around their parents’ index fingers.

Infants admitted to a neonatal intensive care unit may receive up to 60 medications – antibiotics, anesthetics, narcotics, diuretics – in their first month of life. Yet according to a report in the online medical journal STAT, 90% percent of these drugs have not been approved by the FDA for use in newborns.

Instead, doctors make treatment decisions by scaling down from how medications are used in adults: “We take it right out of the vial of an adult drug, dilute it down, and give it to the babies,” says Dr. Jonathan Davis, chief of newborn medicine at Tufts Medical Center. Doctors make decisions based on little more than anecdotes and intuition – essentially treating each sick newborn as an uncontrolled, unapproved study of one.

Result: “There have been some big, big, big mistakes in neonatology through the years when it comes to drugs,” said neonatologist Dr. Matthew Laughon of the University of North Carolina at Chapel Hill. Examples of what’s been admitted to publicly are the sudden deaths of preemies due to too-large doses of the antibiotic chloramphenicol in the 1950s; the fatal poisoning of infants from large amounts of benzyl alcohol, a preservative used to flush catheters, in the 1980s; and deaths from a preservative, propylene glycol, in a multivitamin given orally to premature infants in a dose intended for adults.

This happens because how drugs affect people is strongly age-dependent: infants absorb, metabolize, and excrete drugs differently than adults. “Yet we haven’t done the studies to know exactly what those differences are,” said Catherine Sherwin, chief of pediatric clinical pharmacology at the University of Utah School of Medicine. “We just know they’re different.”

Why is there no medical evidence and no FDA approval process for 90% of the drugs used on newborns? Fear and fear of lawyers: Pharmaceutical companies shy away from studying infants because they are fragile, cannot spare many blood samples, and are vulnerable to permanent injuries – injuries that, in the past, have been awarded large malpractice verdicts. And second, money: Newborns are a small market, so pharmaceutical companies aren’t likely to make money by getting drugs approved for neonate use.

So where does that leave us? “We’ve got to do something,” says Dr. Davis. Without drug data for newborns, he said, “we can’t be certain which drugs, in which doses, to use when.”



“Very few” people who think they have a penicillin allergy actually do


Penicillin 1


Most patients who have a history of penicillin allergy are not really allergic to penicillin.

According to a report this week in JAMAless than 10% [of people] with penicillin allergy histories who are tested in specialized allergy clinics are found to be at risk for acute allergy to penicillin’s.”

Moreover: “Careful assessment of a patient’s history of antibiotic allergy, combined with testing strategies, will result in very few of the estimated 25 million to 30 million US residents labeled as allergic to penicillin to not receive penicillin’s or other [penicillin-like] antibiotics when those drugs are indicated.

So if for any reason you think you’re allergic to penicillin the authors recommend that you arrange for an allergy specialist to do skin testing (above photo).

The reason? Not using penicillin or a penicillin-derivative when you should, means you’re (unnecessarily) using something that is less effective, more toxic, and more expensive. And thus, in hospital settings, you’re facing a “greater risk for prolonged length of stay, readmissions, and acquisition of multidrug-resistant organisms.”

So for example, when you don’t use the antibiotic of choice for Staph aureus:


The inability to use an antistaphylococcal penicillin (e.g. nafcillin) for patients with methicillin-susceptible Staphylococcus aureus sepsis, or other serious infections, for which penicillin’s are the first-line therapy … places patients at risk of treatment failure, resistance generation, and increased mortality.” [My emphasis.]


Childhood penicillin allergies will disappear “in most patients … after a decade.” But there’s another reason why you may think you have a penicillin allergy when you don’t: “… viral rashes in children may be mistaken for penicillin allergy when these children are unnecessarily given antibiotics for a viral syndrome.”





Mean Streets

mtct 2


NPR reports that Trump’s proposed budget will cut over $2 billion dollars from global healthcare spending. It will, for example, eliminate U.S. aid for international family planning. And programs to combat HIV/AIDS in the world’s poorest countries will be slashed by 17 percent. One notable program on the chopping block is the Presidential Emergency Plan for AIDS Relief (PEPFAR) which funds life-saving drugs for infected people as well as prevention efforts.

There will be harm. Reduction in family planning services alone will result in about 3.3 million more abortions, 15,000 more maternal deaths, 8 million more unintended pregnancies, and 26 million fewer women and couples receiving services per year.

Condemnation was swift. This excerpt from a Washington Post op-ed explains why it’s even in America’s best interest to continue these programs and to fully fund them:


It is clear that the generosity of the American people has had a huge impact — one that reflects the view that all lives are precious, and to whom much is given, much is required. This lifesaving work also has a practical purpose for Americans. Societies mired in disease breed hopelessness and despair, leaving people ripe for recruitment by extremists. When we confront suffering — when we save lives — we breathe hope into devastated populations, strengthen and stabilize society, and make our country and the world safer …

Saving nearly 12 million lives is proof that PEPFAR works, and I urge our government to fully fund it. We are on the verge of an AIDS-free generation, but the people of Africa still need our help. The American people deserve credit for this tremendous success and should keep going until the job is done.


An example of how the cuts will hurt is seen with the effort to prevent mother-to-child transmission (MTCT) of HIV: an HIV-positive woman transmits the virus to her child during pregnancy, childbirth or breastfeeding. MTCT accounts for the vast majority of new infections in children. In 2015, 150,000 children – 400 children a day – became infected this way.

If HIV is caught in time and with appropriate lifelong treatment the child and the mother can manage the virus and prevent it from developing into AIDS. But there’s an often-overlooked catch: the people closest to the mother will punish her for having transmitted the virus to her child, and this can have lifelong consequences.

AVERT, an HIV and AIDS charity based in the UK, has documented this. For instance, because HIV is so stigmatized, a mother will not want her friends and neighbors to know for fear of being shunned. To the point where she’ll even avoid going for necessary treatment if she thinks she’ll be found out.

For women who disclose their HIV, they’ll find most husbands won’t accompany them to the prenatal clinic. As men who do are perceived as “weaklings” by their peers. Or worse, men will physically abuse or abandon their wives.

There’s even cases where women are abused by healthcare workers. This is what one woman was told by her doctor:


How can you even think about getting pregnant knowing that you will kill your child because you’re positive?!!!’ He threatened not to see me again if I got pregnant. He told me that I was ‘irresponsible’, a bad mother, and that I was certainly running around infecting other people.


We all internalize messages from those closest to us. As these mothers have. And therefore, AVERT says, they’ll sentence themselves to a lifetime of self-blame and punishment for “not fulfilling traditional gender roles of wife and mother,” and for having been abandoned by friends, family, or their husband.

One more thing: these mothers live with the dread of having to one day answer their child’s question that they know will surely come: Mother, how did I get HIV? And the fear of being pushed away – again – when they tell the truth.

It doesn’t take much to figure this stuff out – if you care to. But these days, the men – and they are mostly men; elderly, white and wealthy – patrolling the mean streets of Washington have turned a blind eye to the lives of others, not just abroad but at home too. It wasn’t always like this: the humane Washington Post op-ed above, and PEPFAR, are both authored by the same person – former president George W Bush.

On Sinusitis: Antibiotics are not necessary in the “vast majority” of cases



There’s a terrific article on sinusitis by Consumer Reports that underscores the Golden Rule of antibiotic usage: Never use them for viral-driven infections – which sinusitis almost always is – because (1) they aren’t doing a thing for what’s wrong with you, thus your condition could worsen, and (2) antibiotics are powerful drugs that produce adverse side-effects – they make you feel worse – in a quarter of the people that use them.

The bottom line: “For acute sinusitis, there are very well-done studies (JAMA) indicating that antibiotics are not necessary in the vast majority of patients, and most people will be able to clear an infection on their own,” says ZaraPatel, MD, assistant professor of Otolaryngology at the Stanford University Medical Center.

The chief concern with them is they can make you sickerFor instance, antibiotic use increases the chances of developing an infection caused by clostridium difficile bacteria that can result in life-threatening diarrhea. Almost half a million Americans contracted the infection in 2011, resulting in 15,000 deaths. Other side effects include stomach problems, dizziness/nausea, rashes, vaginal infections, swelling of the face and throat, and breathing problems. Some antibiotics can even cause permanent nerve damage and torn tendons.

Even if bacteria are the cause, the infections usually clear up on their own in about a week. In the meantime, to loosen mucus and help it drain, drink warm liquids – a salt water gargle helps some people; use a hot shower, bath, or a kettle, to breathe warm, moist air; keep your head propped up when you lie down; and because you’re fighting a virus, it’s important to rest.

But never say never. You would consider an antibiotic if: you get better and then worse again; don’t get better after 10 days; you have a fever of 102 or more; you have severe face pain and tenderness; or you have thick, colored mucus for three or more days in a row.

In any event, the purpose of this and the Consumer Reports article is to help you have a better conversation with your physician. The following video will also help and it provides a nice summary of the issues surrounding sinusitis:


Antibiotic resistance: a Global Issue

Not only does antibiotic resistance (ABR) affect you, but it also affects global populations. Due to the ease of the sharing of genetic material between bacteria and the environmental resilience of many bacterial populations, ABR can spread quickly and efficiently. ABR is found in bacteria spanning dozens of countries around the globe and continues to be a concerning issue.

In the United States alone, a multitude of antibiotic resistant bacteria have been reported by the Center for Disease Control and Prevention. An especially worrying species of bacteria is Streptococcus pneumonia, known to cause bacterial meningitis (a serious condition involving the inflammation of membranes surrounding the brain and spinal chord). The CDC reported 1.2 million cases of antibiotic resistant Streptococcus pneumonia causing an estimated 7000 deaths in the year of 20131. This is just one example from an extensive list of antibiotic resistant strains of bacteria.

Of course, ABR is not an issue isolated to the US, or even North America. Data supplied by countries around the world to the WHO illustrate an ABR epidemic spanning the globe. This table from the BC medical journal adapted from a 2014 WHO report demonstrates the widespread presence of ABR:2

This research further demonstrates ABR as a global issue. The BC Medical Journal also describes examples like MRSA bacteria in hospitals and communities necessitating “requiring second-line treatment” causing increased treatment costs and requiring additional monitoring for side effects.2 ABR not only is detrimental to the health of its patients but also to the healthcare infrastructure surrounding those patients.

ABR is a global issue with many adverse implications making it difficult for physicians and present healthcare infrastructure to provide adequate treatment for those affected by resistant bacteria.


1“Antibiotic Resistance Threats in the United States, 2013.” Center for Disease Control and Prevention. Accessed June 8, 2016.

2Wang, Sophie Y., Diana George, Dale Purych, and David M. Patrick. “Antibiotic Resistance: A Global Threat to Public Health.” BC Medical Journal, 6th ser., 56, no. BCMJ (July 2014).


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