Antibiotic prescribing for kids is frequently inappropriate

Summary: Broad-spectrum antibiotics are very commonly prescribed for kids, especially with respiratory conditions, when they are not indicated.

A study just published in the journal Pediatrics disappointingly documents that antibiotics are still grossly overused in pediatric practice. The authors state:

Antibiotics are commonly prescribed for children with conditions for which they provide no benefit, including viral respiratory infections. Broad-spectrum antibiotic use is increasing, which adds unnecessary cost and promotes the development of antibiotic resistance.”

This is more than a matter of promoting antibiotic-resistant pathogens. As more insight emerges into the profound importance of the human microbiome (indigenous microbial flora), the serious immune and metabolic consequences  implications of damaging the microbial flora are becoming more apparent. The authors set out to…

“…provide a nationally representative analysis of antibiotic prescribing in ambulatory pediatrics according to antibiotic classes and diagnostic categories and identify factors associated with broad-spectrum antibiotic prescribing.”

They examined data from the National Ambulatory and National Hospital Ambulatory Medical Care surveys from 2006 to 2008 for the percentage of visits for patients younger than 18 years for whom antibiotics were prescribed, their category, and the associated diagnoses. The guidelines for judicious use of broad-spectrum antibiotics have obviously not hit home:

“Antibiotics were prescribed during 21% of pediatric ambulatory visits; 50% were broad-spectrum, most commonly macrolides. Respiratory conditions accounted for >70% of visits in which both antibiotics and broad-spectrum antibiotics were prescribed. Twenty-three percent of the visits in which antibiotics were prescribed were for respiratory conditions for which antibiotics are not clearly indicated, which accounts for >10 million visits annually.”

Research is needed to investigate to what degree this may contribute to the rising tide of autoimmune disease and allergy. The authors conclude:

Broad-spectrum antibiotic prescribing in ambulatory pediatrics is extremely common and frequently inappropriate.”

Is antibiotic prophylaxis necessary for dental procedures?

A study published in the International Journal of Oral & Maxillofacial Surgerysuggests that, at least for third molar (‘wisdom tooth’) surgery, taking antibiotics preventively for certain dental procedtures may not be necessary. The authors set out to subject the use of antibiotics to prevent postoperative complications in third molar surgery to scientific scrutiny with a prospective, randomized, double blind, placebo-controlled clinical trial:

“100 patients were randomly assigned to two groups. Each patient acted as their own control using the split-mouth technique. Two unilateral impacted third molars were removed under antibiotic cover and the other two were removed without antibiotic cover. The first group received antibiotics on the first surgical visit. On the second surgical visit (after 3 weeks), placebo capsules were given or vice versa. The second group received antibiotics with continued therapy for 2 days on the first surgical visit and on the second surgical visit (after 3 weeks) placebo capsules were given or vice versa.”

On days 3, 7 and 14 after the surgery patients were evaluated for infection, pain, swelling, temperature and trismus (tonic muscle spasm). What did the data show?

“Of 380 impactions, 6 sockets (2%) became infected. There was no statistically significant difference in the infection rate, pain, swelling, and trismus, and temperature between the two groups.

These findings may well shift the perspective on antibiotic prophylaxis for other dental procedures besides wisdom tooth extraction. The authors conclude:

“Results of the study showed that prophylactic antibiotics did not have a statistically significant effect on postoperative infections in third molar surgery and should not be routinely administered when third molars are removed in non-immunocompromised patients.”

Does colored sputum definitely indicate a need for antibiotics?

Practitioners and patients alike often assume that discolored sputum or discharge is a definite indication of bacterial infection and the need for antibiotics. This assumption is worth testing because, as reported in the previous post, antibiotics given when a respiratory infection is viral impair the immune response. In a study published in the Scandinavian Journal of Primary Health Care the authors look into the matter:

“Sputum colour plays an important role in the disease concepts for acute cough, both in the patients’ and the doctors’ view. However, it is unclear whether the sputum colour can be used for diagnosis of a bacterial infection.”

They obtained sputum samples from 241 patients suffering from acute cough drawn from 42 general practices in Düsseldorf, Germany. They examined the relation of sputum color and microbiological proof of bacterial infection by positive culture and the presence of white blood cells. The correlation was not clear-cut:

“In 28 samples (12%) a bacterial infection was proven. Yellowish or greenish colour of the sputum sample and bacterial infection showed a significant correlation. The sensitivity of yellowish or greenish sputum used as a test for a bacterial infection was 0.79; the specificity was 0.46. The positive likelihood-ratio (+LR) was 1.46.”

In other words, only a 46% likelihood that yellow or green sputum would indicate a bacterial infection. Thus they concluded:

The sputum colour of patients with acute cough and no underlying chronic lung disease does not imply therapeutic consequences such as prescription of antibiotics.

Another study just published in the European Respiratory Journal offers further evidence that discolored sputum cannot be assumed to indicate the need for antibiotics. The authors state:

“We investigated whether discoloured sputum and feeling unwell is associated with antibiotic prescribing and benefit from antibiotic treatment for acute cough/lower respiratory tract infection in a prospective study of 3402 adults in 13 countries.”

The authors investigated the association between producing discoloured sputum and an antibiotic prescription and then the association between an antibiotic prescription and symptom resolution. What did their data show?

“Patients producing discoloured sputum were prescribed antibiotics more frequently than those not producing sputum, unlike those producing clear/white sputum. Antibiotic prescribing was not associated with greater rate or magnitude of symptoms score resolution (as measured by 13 item scale completed by patients each day) among those who: produced yellow or green sputum…”

The authors’ conclusion, along with the detrimental effects of the improper use of antibiotics, should be kept in mind:

“Adults with acute cough/LRTI [lower respiratory tract infection] presenting in primary care with discoloured sputum were prescribed antibiotics more often compared to those not producing sputum. Sputum colour, alone or together with feeling generally unwell was not associated with recovery or benefit from antibiotic treatment.

While yellow or green sputum should not be accepted as sole justification for the use of antibiotics, a study published in the journal Respiratory Care establishes that cream, white or clear sputum is almost guaranteed not to be a bacterial infection. The authors set out to…

“…determine whether the simple characteristic of sputum color provides information that impacts resource utilization such as laboratory testing and prescription of antibiotics.”

They correlated out-patient sputum samples assigned to 8 color categories (green, yellow-green, rust, yellow, red, cream, white, and clear) gram stain and culture results. Their findings for discolored sputum were similar to the other studies:

“Of 289 consecutive samples, 144 (50%) met standard Gram-stain criteria for being acceptable lower-respiratory-tract specimens. In the acceptable Gram-stain group, 60 samples had a predominant organism on Gram stain, and the culture yielded a consistent result in 42 samples (15% of the 289 total specimens). Yield at each level of analysis differed greatly by color. The yield from sputum colors green, yellow-green, yellow, and rust was much higher than the yield from cream, white, or clear.”

Based on their data they offer a clear statement in their conclusion:

If out-patient sputum is cream, white, or clear, the yield from bacteriologic analysis is extremely low. This information can reduce laboratory processing costs and help minimize unnecessary antibiotic prescription.”

It should be noted that these studies concern mainly respiratory infections in an out-patient setting and not severe COPD or cystic fibrosis. Whether antibiotics are indicated or not should be determined by a skilled comprehensive assessment, not by sputum color alone.

Scandinavian Journal of Primary Health Care

Antiobiotics impair immune response to the flu

It’s not just that antibiotics don’t help a viral infection, an important paper just published in the Proceedings of the National Academy of Sciences (USA) demonstrates that they impair the immune response to the flu. The authors state:

“Although commensal bacteria are crucial in maintaining immune homeostasis of the intestine, the role of commensal bacteria in immune responses at other mucosal surfaces remains less clear. Here, we show that commensal microbiota composition critically regulates the generation of virus-specific CD4 and CD8 T cells and antibody responses following respiratory influenza virus infection.”

They investigated various antibiotic treatments and found that neomycin-sensitive bacteria required to produce protective immune responses in the lung.

Intact microbiota provided signals leading to the expression of mRNA for pro–IL-1β and pro–IL-18 at steady state. Following influenza virus infection, inflammasome activation led to migration of dendritic cells (DCs) from the lung to the draining lymph node and T-cell priming.”

In other words, the normal bacterial residing in the intestines (that are wiped out by common antibiotics) play a critical role in the cellular signaling necessary to mount an immune antiviral response. The authors conclude:

“Our results reveal the importance of commensal microbiota in regulating immunity in the respiratory mucosa through the proper activation of inflammasomes.”

An ‘editor’s choice’ essay published in Science Signaling commenting on this important study observes:

“Both virion-specific antibody titers and T cell responses (interferon-{gamma} production and number of cytotoxic T cells) were decreased in antibiotic-treated mice compared with untreated controls, and pulmonary viral titers were increased…The adaptive immune response to respiratory infection with influenza depends on activation of inflammasomes…such as interleukin-1β (IL-1β) and IL-18…Antibiotic treatment decreased the abundance of the mRNAs encoding pro–IL-1β, pro–IL-18, and NLRP3 even before infection, as well as postinfection secretion of mature IL-1β, suggesting that commensal bacteria provide a constitutive priming signal. Antibiotics also inhibited migration of respiratory dendritic cells to lymph nodes to activate T cells…Thus, the authors propose that commensal bacteria provide a signal required for inflammasome-dependent immune responses to respiratory infection, which is lost with antibiotic-mediated disruption of the microbiota.”

Bottom line: wiping out commensal bacterial with antibiotics hobbles the immune response to viral respiratory infection.

Taking probiotics after antibiotics is not the same as with intact gut flora

An interesting study just published in the journal Genome Research examines the differing effects of introducing microflora into the gut environment with and without prior antibiotic treatment. The authors note:

“The intestinal microbiota consists of over 1000 species, which play key roles in gut physiology and homeostasis. Imbalances in the composition of this bacterial community can lead to transient intestinal dysfunctions and chronic disease states. Understanding how to manipulate this ecosystem is thus essential for treating many disorders.”

They employed recent technological advances to examine by DNA analysis the long-term effects of transplanting bacteria into the intestine with and without antibiotic pretreatment. Their findings were most interesting:

“The transplantation produced a marked increase in the microbial diversity of the recipients, which stemmed from both capture of new phylotypes and increase in abundance of others. However, when transplantation was performed after antibiotic intake, the resulting state simply combined the reshaping effects of the individual treatments (including the reduced diversity from antibiotic treatment alone). Therefore, lowering the recipient bacterial load by antibiotic intake prior to transplantation did not increase establishment of the donor phylotypes…Remarkably, all of these effects were observed after 1 mo of treatment and persisted after 3 mo.”

In other words, rather than opening a niche for the transplantation of beneficial flora, engendering a diverse microbial ecology was inhibited by the destruction of organisms and change in gut homeostasis by the antibiotic.  Moreover, the effects are long-lasting. The authors conclude by stating:

“Overall, our results indicate that the indigenous gut microbial composition is more plastic that previously anticipated. However, since antibiotic pretreatment counterintuitively interferes with the establishment of an exogenous community, such plasticity is likely conditioned more by the altered microbiome gut homeostasis caused by antibiotics than by the primary bacterial loss.”

Clinicians should take this into consideration when charting a course for the re-establishment of a healthy gut microbial ecology. Patients should understand that it may take a long time and may not be easy as it goes through a sequence of stages.

Probiotics treat mastitis better than antibiotics

Clinical Infectious DiseasesA study published last month in the journal Clinical Infectious Diseases offers an interesting surprise about the treatment of mastitis (infection of the breast).

Mastitis is a common infectious disease during lactation, and the main etiological agents are staphylococci, streptococci, and/or corynebacteria. The efficacy of oral administration of…two lactobacilli strains isolated from breast milk, to treat lactational mastitis was evaluated and was compared with the efficacy of antibiotic therapy.”

What happened to the women who took probiotics instead of antibiotics?

“On day 21, the mean bacterial counts in the probiotic groups were lower than that of the control group…Women assigned to the probiotic groups improved more and had lower recurrence of mastitis than those assigned to the antibiotic group.”

Of course there is the obvious advantage of not decimating the patient’s microbial ecology. This impressive result, summed up in the authors’ conclusion, is worth bearing in mind if you’re nursing a baby who caring for someone who is:

“The use of L. fermentum CECT5716 or L. salivarius CECT5713 appears to be an efficient alternative to the use of commonly prescribed antibiotics for the treatment of infectious mastitis during lactation.”

Antibiotics during pregnancy and risk of birth defects

Ladies, if you absolutely have to take an antibiotic during pregnancy note the results of this study just published in the Archives of Pediatrics & Adolescent Medicine. Avoid sulfonamides and nitrofurantoins (quinolones are generally not recommended while pregnant). Penicillins, erythromycins, and cephalosporins were associated with less birth defects.