{"id":6499,"date":"2026-04-10T13:05:21","date_gmt":"2026-04-10T19:05:21","guid":{"rendered":"https:\/\/allphasepharma.com\/dir\/?p=6499"},"modified":"2026-04-10T13:05:25","modified_gmt":"2026-04-10T19:05:25","slug":"treating-serious-crab-infections","status":"publish","type":"post","link":"https:\/\/allphasepharma.com\/dir\/2026\/04\/10\/6499\/treating-serious-crab-infections\/","title":{"rendered":"Treating Serious CRAB Infections"},"content":{"rendered":"\n
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There are MDR pathogens, and there is carbapenem-resistant A. baumannii, aka CRAB.<\/p>\n\n\n\n

This surely must be one of the most formidable bacterial organisms. It has resistance mechanisms second to none.\u00a0 When found in patients, it is very difficult to eradicate and extremely difficult to get rid off, once established in hospitals.\u00a0 So far in the US, we rarely have to deal with carbapenem-resistant organisms; CRAB is more prevalent in some European countries such as Spain, Italy, and Turkey.\u00a0 Southeast Asia probably has the highest prevalence and incidence of CRAB patients.\u00a0 Intensivists likely have to deal with this pathogen; it is often the last organism standing after several rounds of antibiotic therapy.\u00a0<\/p>\n\n\n\n

Hospitals are not proud admitting they have an \u2018Acinetobacter problem\u2019, which leads us to believe that infections are greatly underreported.\u00a0 We have heard from ICUs in the Middle East that had to deal with CRAB infections routinely, mostly unreported.\u00a0<\/p>\n\n\n\n

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No article on CRAB should omit a reference to the ordeal Dr. Thomas Patterson had to go through. He acquired a life-threatening CRAB infection as a tourist in Egypt. The book, written by his wife, is highly recommended for anyone who wants to learn more about CRAB, its virulence and the challenges clinicians and patients face.[1]<\/a> An investigational cocktail of phages finally controlled his infection, which did not respond to any existing antibacterials. We agree with the book reviews below: a medical thriller.<\/p>\n\n\n\n

“A memoir that reads like a thriller”<\/strong>
New York Times Book Review<\/em>
“A fascinating and terrifying peek into the devastating outcomes of antibiotic misuse-and what happens when standard health care falls short”<\/strong>
Scientific American<\/em><\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n

Cascio et al. wrote an up-to-date article on CRAB therapies.[2]<\/a>\u00a0<\/p>\n\n\n

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Cefiderocol<\/figcaption><\/figure>\n<\/div>\n\n
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The authors provide an excellent review of literature, a messy task as most \u2018studies\u2019 are retrospective and uncontrolled. Reviewers have to deal with case series, combination therapies, and methodological problems.\u00a0 Most of hese anecdotal \u2018studies\u2019\u00a0are low quality publications that take up an inordinate amount of space in most reviews, disproportionate to their value.<\/p>\n\n\n\n

In situations like this, it becomes difficult to separate fluff from the few hard facts we have.\u00a0All too often the PK\/PD properties of the drugs we use for CRAB infections are ignored. Mind you, we are talking about CRAB, not the carbapenem-susceptible acinetobacters for which treatment is easier. Likewise, we are focusing on severe CRAB infections, like HAP\/VAP and bacteremia, not skin infections or UTIs.<\/p>\n\n\n\n

Bottom line: One cannot rely on tigecycline or the polymyxins for severe respiratory CRAB infections.<\/strong><\/p>\n\n\n\n

Tigecycline<\/strong> is still being used, mainly because clinicians only look at its in-vitro<\/em> activity against CRAB which is misleading.\u00a0Intensivists like to use the drug off-label at high IV doses (100 mg IV q12h) for HAP\/VAP as it is well tolerated, thinking that ‘more is better’.\u00a0 However, there is absolutely no evidence higher doses improve outcomes. Several pharmacologists have pointed out that higher doses do not increase levels of free tigecycline, a rare paradoxical effect.\u00a0
Tigecycline is bacteriostatic, not bactericidal and has poor lung and ELF penetration. Tigecycline is a drug with a low free (unbound) fraction; free AUC is the PK determinant of efficacy.\u00a0This makes a direct application of MIC data to the clinical situation problematic; it is the probable reason of the failure of several tigecycline trials for pneumonia.\u00a0
Pfizer has never conducted prospective clinical studies with tigecycline in acinetobacter infections, let alone CRAB.\u00a0 Therefore, the clinical practice of using low- or high-dose tigecycline is hard to defend.<\/p>\n\n\n\n

Cascio et al. do not recommend tigecycline for any serious CRAB infection,
pulmonary or otherwise<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n

Polymyxin \/ Colistin <\/strong>are drugs with exceptionally low MICs for all acinetobacters, including CRAB.\u00a0 As such they have become the ‘go-to agents’ for serious infections, despite the recognized toxicity, mainly related to dose and treatment duration.\u00a0 Mandell\u2019s textbook has a lengthy section on both drugs, with much ink spilled over the rather confusing dosing recommendations [3]<\/a>, [4]<\/a>.\u00a0 The authors pointedly state that a therapeutic level can only be achieved in the presence of reduced GFR.\u00a0 In other words: these drugs are underdosed out of concern for nephrotoxicity, an inevitable side effect with more prolonged therapy.\u00a0 On top of this, they have poor lung penetration.\u00a0 Taken together, the drug levels of polymyxin \/ colistin are likely subtherapeutic if prescribed according to label.\u00a0
Since their entry into clinical use in the mid-60s, they have not been studied thoroughly, as newer and less toxic antibiotics have replaced them.<\/p>\n\n\n\n

Cascio et al. state that polymyxin \/ colistin is NOT appropriate for pneumonia caused by CRAB infection<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n

We also agree and support the other \u201cCLINICS CARE POINTS\u201d at the end of the Cascio article regarding the use of cefiderocol and SUL\/DUR.\u00a0<\/p>\n\n\n\n

The following are some additional thoughts from our vantage point:<\/p>\n\n\n\n