Why is doxycycline unavailable

Only outbreaks of Panton-Valentine leukocidin-positive, doxycycline-resistant, methicillin-susceptible Staphylococcus aureus infections have been linked to long-term chemoprophylaxis with doxycycline in soldiers under deployment [ 63 ]. There is no published information on the development of bacterial resistance after short-courses of doxycycline used in malaria prophylaxis. Doxycycline was developed after tetracycline and was labelled with the same side-effects as the earlier tetracyclines, including the risk of yellow tooth discolouration and dental enamel hypoplasia in children under 8 years of age.

In the United States, the CDC have recommended the use of doxycycline for the treatment of acute and chronic Q fever and tick-borne rickettsial diseases in young children. It is time to rehabilitate doxycycline and to recommend it in combination with the use of quinine for malaria treatment when ACT is unavailable or when the treatment of severe malaria with artesunate fails, in children under 8 years of age.

Doxycycline could also be associated with long-half-life drugs such as amodiaquine, piperaquine or sulfadoxine—pyrimethamine in young children for IPTsc. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Tiphaine Gaillard, Email: moc. Marylin Madamet, Email: moc. Bruno Pradines, Email: moc. National Center for Biotechnology Information , U. Journal List Malar J v. Malar J. Published online Apr Author information Article notes Copyright and License information Disclaimer. Corresponding author. Received Nov 21; Accepted Apr 4. This article has been cited by other articles in PMC. Abstract Anti-malarial drug resistance to chloroquine and sulfadoxine—pyrimethamine has spread from Southeast Asia to Africa.

Potential for adverse dental effects Tetracycline compounds have been used since Discussion These different studies showed that short courses of doxycycline in children under 8 years of age had no visible dental effects, such as staining of teeth or enamel hypoplasia. Conclusions Doxycycline was developed after tetracycline and was labelled with the same side-effects as the earlier tetracyclines, including the risk of yellow tooth discolouration and dental enamel hypoplasia in children under 8 years of age.

Acknowledgements Not applicable. Competing interests The authors declare that they have no competing interests. Contributor Information Tiphaine Gaillard, Email: moc. References 1. World Malaria Report Geneva: World Health Organization; Limited geographical origin and global spread of sulfadoxine-resistant dhps alleles in Plasmodium falciparum populations.

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Likewise, we found limited evidence to support minocycline monotherapy in severe infections or in confirmed S pneumoniae infection. The reviewed data for minocycline in CAP were positive but mostly limited to M pneumoniae infection. In considering the outpatient treatment of young otherwise healthy patients—where atypical organisms primarily M pneumoniae may be of more concern—minocycline could be used within the same framework in which doxycycline is recommended.

Our recommendation also takes into consideration the increased vaccination for pneumococcus and the typically severe presentation of Legionnaires' disease [ 66 ]. Overall, empirical tetracycline monotherapy should be reserved for uncomplicated cases of CAP [ 18 ]. Contrary to this narrow recommendation, there is compelling data to support minocycline's use in CAP specifically caused by macrolide-resistant M pneumoniae [ 27—30 ].

Considering the increased incidence of macrolide-resistance M pneumoniae in the United States and globally [ 67 ], there will likely be an increased need for tetracycline therapy in CAP. Furthermore, there is increased attention to the cardiovascular risk profile of macrolides and fluoroquinolones, both of which are commonly used for empirical coverage of atypical pathogens in CAP [ 68 , 69 ]. In circumstances in which there is concern for treating macrolide-resistant M pneumoniae or when doxycycline would be preferred for empirical atypical coverage, we recommend substituting minocycline for doxycycline.

At this time, the CDC only recommends doxycycline as an option for Lyme disease prophylaxis due to lack of evidence with other medications. The CDC specifically recommends against single-dose amoxicillin due to its short half-life eg, approximately 1 hour [ 1 , 70 ].

Minocycline appears effective in the treatment of early Lyme disease [ 31—36 ]. Unfortunately, we found no data regarding minocycline for Lyme disease prophylaxis following tick bite. However, most studies regarding prophylaxis are equivocal due to the low event rate [ 71—75 ]. The most recent guideline from the IDSA includes an option for prophylaxis with single-dose doxycycline in patients meeting strict criteria [ 76 ]. Therefore, when prophylaxis is indicated in the absence of doxycycline, we recommend clinicians consider minocycline and exercise shared decision making [ 77 ].

We recommend that this conversation include at least 5 key points: 1 the overall risk of developing Lyme disease is low and forgoing prophylaxis may be reasonable; 2 there are effective treatments for early Lyme disease; 3 the benefit of antibiotic prophylaxis is small and may be offset by the risk for adverse effects with antibiotic treatment; 4 doxycycline is usually recommended, however, if unavailable, minocycline is a similar but less studied antibiotic; and 5 although minocycline may work better, as well, or not as well other antibiotics, it is suggested as a potential alternative because it works similarly to doxycycline, and it has been shown to be effective in patients who have developed Lyme disease.

The literature to support the use of minocycline in rickettsial diseases is severely limited. Although the included report of Japanese spotted fever had a rate of life-threatening disease on par with Rocky Mountain spotted fever—the most common rickettsial disease in the United States—it is difficult to use these data as a surrogate. Rocky Mountain spotted fever is a circumstance that warrants retaining a supply of doxycycline in endemic areas. However, the CDC did not definitively recommend alternative therapy should doxycycline be entirely unavailable [ 1 ].

Therefore, we pose that it is worthy to consider minocycline's place in therapy for Rocky Mountain spotted fever—given its lethality—in the scenario of complete doxycycline unavailability.

Older and in vitro data demonstrate that tetracycline may be a potential alternative to doxycycline [ 78—80 ]. To our knowledge, there are no reports of increasing resistance of Rickettsia rickettsii to any tetracycline antibiotic. Considering minocycline and doxycycline's similar pharmacokinetic and susceptibility profiles, we portend minocycline to be a potential alternative, despite the dearth of clinical data. Important in this consideration is that further alternatives may be considerably less desirable.

The CDC mentions the potential use of chloramphenicol as an alternative to doxycycline [ 1 ]. However, the CDC rightly notes that chloramphenicol is associated with a greater mortality risk compared with treatment regimens that include a tetracycline. This fact is supported by 2 large surveillance studies that demonstrate chloramphenicol monotherapy to be statistically associated with fatal disease compared with treatment with any tetracycline as monotherapy or with any tetracycline in combination with chloramphenicol [ 81 , 82 ].

Unfortunately, these studies did not delineate the different tetracycline agents used. Considering the lethality of Rocky Mountain spotted fever and the potential inferiority of chloramphenicol monotherapy, we recommend treatment with either minocycline or tetracycline in combination with chloramphenicol over chloramphenicol monotherapy in the absence of doxycycline.

The limitations of these data are significant and more research—including observational and retrospective reports—is greatly needed. We make this tenuous recommendation because there is the potential for this circumstance to occur and no direct guidance from the CDC or other authorities.

In conclusion, drug shortages interfere with the management of infectious diseases and necessitate the use of less familiar alternatives.

This systematic review supports the use of minocycline as a substitute for doxycycline in SSTIs, an alternative in the outpatient treatment of CAP in young otherwise healthy patients with more evidence in macrolide-resistant M pneumoniae , an alternative to doxycycline for Lyme disease prophylaxis should prophylaxis be strongly desired and doxycycline is unavailable , and a last alternative in select rickettsial diseases should doxycycline be entirely unavailable.

Given the myriad of indications for which doxycycline can be used, further research, review, and guidance are needed to prepare practitioners, institutions, and health systems to provide adequate care in the face of tetracycline shortages and antibiotic shortages in general.

The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government.

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