The 1st edition of Mandell’s textbook ‘Principles and Practice of Infectious Disease’ was published in 1979. It has grown ever since in size and numbers of chapters. Now in its 10th edition, it is and remains an impressive publication, a 2-volume set, a comprehensive reference textbook, kept up-to-date with periodic electronic additions.
We cannot provide a review here, as we only studied some chapters in depth. What we can say is that authorship in the latest edition (2025) is noticeably more international than in past years. Nonetheless, there are still some experts, long retired, writing ‘their’ chapters as if they ‘owned’ a certain disease area. A gradual hand-over to a new generation is underway, and this is good.
Despite its large size, we have a suggestion for an additional chapter, on a topic totally ignored in all editions including the latest. We noticed this gap, as we were reading up on an old antibiotic, chloramphenicol (CAM).
Chapter 25 by Moffa and Brook in Mandell’s 10th edition is entitled ‘Tetracyclines, Tetracycline Derivatives, and Chloramphenicol’. The title does not mention CAM derivatives, only thiamphenicol is mentioned in the chapter, in passing. Is this an oversight or truly reflecting lack of progress? It almost appears that time stood still, as none of the approx. 240 references dealing with CAM are of recent vintage. The most recent one is from the year 2012; it is about Acinetobacter susceptibility that mentions CAM in passing.
This is odd for a variety of reasons. Given our ‘empty pipeline’ for antibacterials, one would expect interest in novel, less bone marrow toxic CAM derivatives. This kind of R&D gave us the 2nd and 3rd generation tetracyclines (tigecycline, omadacycline, eravacycline), after all. Why wasn’t there a similar effort to find CAM congeners?
First, we read that CAM derivatives are difficult to synthetize. [6],[7] Second, the aplastic anemia side effect is a significant worry that looms large. Lacking a full understanding of its etiology, the fear of a potential class effect carries over to any newly synthesized ‘phenicol’ that shares the basic structure. Of course, there is the practical convenience factor: we still have plenty of safer alternative antibiotics for the indications for which CAM was used traditionally, like meningitis, enteric fever, other GI infections, and respiratory infections. Not to mention lack of patent life…
On the other hand, we could argue that bacterial multi-drug resistance is a fact of life, and we need new antibiotics to overcome resistance. The feared idiosyncratic aplastic anemia with CAM is most likely due to the p-nitrophenol group, and thiamphenicol is proof positive thereof. This drug has seen decades of use; it is available in most parts of the world, just not in the US. The latter has the typical CAM spectrum and similar PK for PO and IV use; as shown below, it does not have the ominous p-nitro benzene group. It has never been associated with aplastic anemia. We would consider thiamphenicol as having a very favorable set of features for any antibacterial candidate drug, old or new.
The same goes for florfenicol, a drug much used in veterinary medicine. Different structure, no aplastic anemia.
What is florfenicol? Relegated to veterinary use in livestock animals and salmon aquaculture, it is not mentioned in Mandell’s 10th edition at all. This is surprising as veterinary use of antibiotics clearly impacts resistance development that carries over to human use. Here is our point: There should be a chapter on the veterinary use of antibiotics in Mandell’s, as antibiotic use (in tonnes) in animals is almost 4x larger than for humans.
There is a flurry of publications on florfenicol (sometimes spelled fluphenicol or flufenicol). Most are concerned with environmental contamination and lack of biodegradation, given its chemical stability conferred by high bond energy. Supra-therapeutic concentrations were found in aquaculture. [1],[2],[3] Other articles deal with dose-dependent toxicities and effects on endocrine / reproductive system and, yes, resistance development.
It is well known that tetracyclines, quinolones like enrofloxacin, and sulfa drugs are widely used in veterinary medicine. Florfenicol has attracted considerably less attention despite huge production, sales and use figures.
“The Florfenicol Market size was valued at USD 412 million in 2025 and is expected to reach USD 644.32 million by 2034, growing at a CAGR of 5.1% from 2025 to 2034”
“An estimated 14,800 metric tons of florfenicol were consumed worldwide in 2024” [4]
By comparison, ciprofloxacin production figures look anemic: For North America, the ciprofloxacin API market is a mere 2,200 tons annually according to a recent market report.[5]
Florfenicol is only one in a long list of CAM derivatives. We were curious and looked for another halogenated CAM derivative. Is there a bromphenicol, or an iodine-substituted CAM? Indeed, among some 300 structurally modified phenicols synthesized since the 1950s, we found bromamphenicol. It is described as having weak antimicrobial activity by some, and strong activity by others. In the absence of comparative micro data, we cannot verify or refute these contradictory claims.
For the interested reader, two recent publications provide reviews about recent efforts to synthesize CAM derivatives.[6],[7]
We would hope the editors of Mandell’s textbook could find space for a chapter on “Antibiotics in Veterinary Medicine” in the next edition.
No need to buy the new Mandell’s PPID in order to get an update on CAM;
earlier editions contain much the same information
REFERENCES
[1] Zhang H. Unlocking the potential of pyrite by mechanochemistry ball mill for efficient heterogeneous Fenton degradation of florfenicol. J Cleaner Production 541, 2026: 147515
[2] Hayes J. Stability of Florfenicol in Drinking Water. J AOAC Internat 86, 2003: 22
[3] He X. Sequential treatment of UV254 photodegradation and microalgal bioremediation in aquaculture effluent: Florfenicol toxicity mitigation and nutrient recovery. J Hazardous Materials 500, 2025: 140393
[4] 360 Research Report. https://www.360researchreports.com/market-reports/florfenicol-market-209248 (accessed Feb 11, 2026)
[5] Market Research Report, 2025-2032. Published 2025. https://datavagyanik.com/reports/ciprofloxacin-api-market/ (accessed Feb 11, 2026)
[6] Dinos G. Chloramphenicol Derivatives as Antibacterial and Anticancer Agents: Historic Problems and Current Solutions. Antibiotics 2016, 5: 20
[7] Tevyashova A. Recent Trends in Synthesis of Chloramphenicol New Derivatives. Antibiotics 2021, 10, 370
