Antibiotic treatment for Shigella infections

Klontz KC, Singh N. Treatment of drug-resistant Shigella infections. Expert Rev Anti Infect Ther. 2015 Jan;13(1):69-80.

Since the introduction of sulfonamides in the late 1930s, selective pressure and the widespread dissemination of mobile genetic elements conferring antimicrobial resistance have forced clinicians to seek successive agents for the treatment of multidrug-resistant shigellosis. Over the decades, the principal antibiotics used to treat Shigella infections have included tetracycline, chloramphenicol, ampicillin, trimethoprim-sulfamethoxazole, and nalidixic acid. Presently, ciprofloxacin, azithromycin, and ceftriaxone serve as the mainstays of treatment, although growing evidence has documented decreased susceptibility or full resistance to these agents in some regions. With diminishing pharmaceutical options available, there is an enhanced need for preventive measures in the form of improved sanitation and hygiene standards, strict use of currently effective agents, and a safe and effective licensed vaccine.

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Holmes LC. Shigella. Pediatr Rev. 2014 Jun;35(6):261-2.

“The choice of which antibiotic to administer is another treatment question. A 2010 Cochrane review of 16 randomized controlled trials evaluating antibiotics for shigella dysentery found all classes of antibiotics had similar efficacy, and the authors were not able to identify a superior class of antibiotics. In the United States, the 2010 National Antimicrobial Resistance Monitoring System found 41% of Shigella species resistant to ampicillin, 48% resistant to trimethoprim-sulfamethoxazole, 2% resistant to ciprofloxacin, and less than 1% resistant to ceftriaxone. Antibiotic resistance in outbreaks has been reported to be much higher. Arvelo et al found 90% of the Shigella strains involved in a large daycare center–associated outbreak resistant to both ampicillin and trimethoprim-sulfamethoxazole. Knowing regional resistance patterns and the susceptibility pattern of the pathogen once available is essential to guide therapy.”

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Christopher PR, et al. Antibiotic therapy for Shigella dysentery. Cochrane Database Syst Rev. 2010 Aug 4;(8):CD006784.

Antibiotics reduce the duration of Shigella dysentery.Regularly updated local or regional antibiotic sensitivity patterns to different species and strains of Shigella are required to guide empiric therapy. More trials adhering to standard guidelines are required to evaluate the role of antibiotics in the treatment of severe forms of Shigella dysentery and in groups who are at high risk of complications.

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Antibiotics for appendicitis (focus on perforated appendicitis)

Kronman MP, et al. Extended- Versus Narrower-Spectrum Antibiotics for Appendicitis. Pediatrics. 2016 Jul;138(1). pii: e20154547.

“This large, multicenter study found no advantage of empiric extended-spectrum antibiotic therapy for children with uncomplicated or complicated appendicitis. Given these findings and the frequency of extended-spectrum antibiotic use for this condition, pediatric appendicitis represents an important target for antimicrobial stewardship efforts. A prospective study could determine the optimal antibiotic selection for those with complicated appendicitis.”

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Lee JY, et al. Once Daily Dosing of Ceftriaxone and Metronidazole in Children With Perforated Appendicitis. J Pediatr Pharmacol Ther. 2016 Mar-Apr;21(2):140-5.

While there was no statistically significant difference in the outcomes evaluated, the rate of infectious complications was twofold higher in those given ceftriaxone and metronidazole than in others. A larger prospective randomized controlled trial is warranted to better understand the risks of using these agents.

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Antibiotic prophylaxis for urinary tract infections

Brandström P, Hansson S. Long-term, low-dose prophylaxis against urinary tract infections in young children. Pediatr Nephrol. 2015 Mar;30(3):425-32.

Urinary tract infection (UTI) affects about 2 % of boys and 8 % of girls during the first 6 years of life with Escherichia coli as the predominant pathogen. Symptomatic UTI causes discomfort and distress, and carries a risk of inducing renal damage. The strong correlation between febrile UTI, dilating vesicoureteral reflux (VUR), and renal scarring led to the introduction of antibiotic prophylaxis for children with VUR to reduce the rate of UTI recurrence. It became common practice to use prophylaxis for children with VUR and other urinary tract abnormalities. This policy has been challenged because of a lack of scientific support. Now, randomized controlled studies are available that compare prophylaxis to no treatment or placebo. They show that children with normal urinary tracts or non-dilating VUR do not benefit from prophylaxis. Dilating VUR may still be an indication for prophylaxis in young children. After the first year of life, boys have very few recurrences and do not benefit from prophylaxis. Girls with dilating VUR, on the other hand, are more prone to recurrences and benefit from prophylaxis. There has been a decline in the use of prophylaxis due to questioning of its efficacy, increasing bacterial resistance, and a propensity to low adherence to medication. Alternative measures to reduce UTI recurrences should be emphasized. However, in selected patients carefully followed, prophylaxis can protect from recurrent UTI and long-term sequelae. 1. There is a strong correlation between UTI, VUR, and renal scarring. 2. Children with normal urinary tracts or non-dilating VUR do not benefit from prophylaxis. 3. Young children, mainly girls, with dilating VUR are at risk of recurrent UTI and acquired renal scarring and seem to gain from antibiotic prophylaxis. 4. Increasing bacterial resistance and low adherence with prescribed medication is a major obstacle to successful antibiotic prophylaxis.

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Toxic shock syndrome and clindamycin

American Academy of Pediatrics. Group A Streptococcal Infections. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book®: 2015 REPORT OF THE COMMITTEE ON INFECTIOUS DISEASES. American Academy of Pediatrics; 2015; 732-744.

TOXIC SHOCK SYNDROME: “As outlined in Tables 3.70 and 3.71 (p 740), most aspects of management are the same for toxic shock syndrome caused by group A streptococci or by S aureus. Paramount are immediate aggressive fluid replacement management of respiratory and cardiac failure, if present, and aggressive surgical débridement of any deep-seated infection. Because S pyogenes and S aureus toxic shock syndrome are difficult to distinguish clinically, initial antimicrobial therapy should include an antistaphylococcal agent and a protein synthesis-inhibiting antimicrobial agent, such as clindamycin. The addition of clindamycin to penicillin is recommended for serious GAS infections, because the antimicrobial activity of clindamycin is not affected by inoculum size (does not have the Eagle effect that can be observed with the beta-lactam antibiotics), has a long postantimicrobial effect, and acts on bacteria by inhibiting protein synthesis. Inhibition of protein synthesis results in suppression of synthesis of the S pyogenes antiphagocytic M-protein and bacterial toxins. Clindamycin should not be used alone as initial antimicrobial therapy in life-threatening situations, because in the United States, 1% to 2% of GAS strains are resistant to clindamycin. Higher resistance rates have been reported for strains associated with invasive infection and may be as high as 10%.

Once GAS infection has been confirmed, antimicrobial therapy should be tailored to penicillin and clindamycin. Intravenous therapy should be continued until the patient is afebrile and stable hemodynamically and blood is sterile as evidenced by negative culture results. The total duration of therapy is based on duration established for the primary site of infection.”

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Article of Interest: Impact of antibiotic pretreatment on bone biopsy yield for children with acute hematogenous osteomyelitis.

Zhorne DJ, Altobelli ME, Cruz AT. Impact of antibiotic pretreatment on bone biopsy yield for children with acute hematogenous osteomyelitis. Hosp Pediatr. 2015 Jun; 5(6): 337-41.

OBJECTIVE: Pediatric acute hematogenous osteomyelitis (AHO) is a relatively common reason for hospitalization, but many variables require additional study, including the impact of antibiotic treatment on bone biopsy culture yield.

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EBM Review: Comparative effectiveness of intravenous vs. oral antibiotics for postdischarge treatment of acute osteomyelitis in children.

Keren R, Shah SS, Srivastava R, et al. Comparative effectiveness of intravenous vs. oral antibiotics for postdischarge treatment of acute osteomyelitis in children. JAMA Pediatr. 2015 Feb;169(2):120-8.

Reviewed by:

Damon Jones, MD Damon Jones, MD PGY-3

Jane Stremming, MD Jane Stremming, MD PGY-3

Background:

  • Osteomyelitis is a relatively uncommon infection in pediatrics
    • Incidence of about 2 – 13/100,000 in developed countries, higher in developing countries
  • Mean age of diagnosis is 6.6 years
    • 40% occur in pre-school aged children
  • Male: Female 1.82:1
  • Risk factors include blunt trauma (30%) and recent systemic infection (37%)
    • No identified risk factors in nearly half of all cases (47%)
  • Presenting symptoms include pain (81%), localized signs symptoms (70%), fever (62%), reduced ROM (50%), and reduced weight bearing (50%)
  • ESR and CRP usually elevated on presentation (91 and 81%, respectively)
    • WBC elevated in only 36% of cases

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Article of interest: Antibiotic exposure in infancy and risk of being overweight in the first 24 months of life.

Saari A, Virta LJ, Sankilampi U, Dunkel L, Saxen H. Antibiotic exposure in infancy and risk of being overweight in the first 24 months of life. Pediatrics. 2015 Apr;135(4):617-26.

OBJECTIVE: Antibiotics have direct effects on the human intestinal microbiota, particularly in infancy. Antibacterial agents promote growth in farm animals by unknown mechanisms, but little is known about their effects on human weight gain. Our aim was to evaluate the impact of antibiotic exposure during infancy on weight and height in healthy Finnish children.

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Minocycline for acne: potential adverse effects

Garner SE, Eady A, Bennett C, Newton JN, Thomas K, Popescu CM. Minocycline for
acne vulgaris: efficacy and safety. Cochrane Database Syst Rev. 2012 Aug 15;8: CD002086.

“In summary, there is no evidence to support the first-line use of minocycline in the treatment of acne. All of the trials showed that, on average, people treated with minocycline experienced an improvement in their acne. However, no study conclusively showed any important clinical difference between minocycline or other commonly-used therapies. The analysis found that minocycline may act more quickly than oxytetracycline or tetracycline, but there is no overall difference in the end. There is no evidence that it is more effective in acne that is resistant to other therapies, or that the effects last longer. Although it is often claimed that the more expensive once-daily slow-release preparation is a more attractive option to teenagers with acne, the evidence in this review does not show it to be any better or safer compared to other oral antibiotics that have to be taken more frequently.

Despite a thorough search for evidence, it is still not known which of the tetracyclines are the safest to take overall as they are all associated with side-effects. The only conclusion that we could make was that people treated with minocycline for acne are at a significantly greater risk of developing an autoimmune (lupus-like) syndrome than those given tetracycline or no treatment.”

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