The Several Agues of Charybdis

From Amoeba Dick, chapter 11.

Circe’s brute swineman
bathed with nymphs in Charybdis.
First rash, then pustules.

One day in 1948, the inventor Candido Jacuzzi appropriated one of the hydraulic pumps manufactured by the family firm at their factory in Chino, California. Candido took the pump home and fitted it to the family bathtub, hoping to replicate at home the hydrotherapy treatment, which his son Kenny had been receiving in hospital for his chronic rheumatoid arthritis. In 1955, Jacuzzi Brothers began to market the pump – by now known as the J300 – to the bathroom supply industry. In 1968, the first fully integrated whirlpool baths went on sale, followed in the early 1970’s by larger units with integrated heating and filtration systems, much akin to the whirlpools and hot tubs of the modern age.

The first reports of infection associated with the use of hot tubs date from this period. These early reports for the most part implicate Pseudomonas aeruginosa as the infecting agent, with Pseudomonas dermatitis or folliculitis as the most common diagnosis.

The genus Pseudomonas to which the pathogenic P.aeruginosa belongs is defined as a Gram-negative aerobic gammaproteobacteria. Other Pseudomonadinae include the plant pathogen P.syringae, which has also been associated with the formation of snow.

The following description of presenting symptoms, fairly typical of the first reports, relates to a 1984 outbreak, centred around a whirlpool in a hotel in St John, Newfoundland:-

“the rash began as a pruritic erythematous papule which progressed to erythematous macules or erythematous pustules. The lesions were distributed in the axilla and over the abdomen and buttocks area.” [Ratnam et al 1985 p655].

This is of a piece with a discussion summarising several earlier case reports, declaring that

“the predominant complaint has been rash; lesions are papulovesicular on an erythematous base, 2 to 5mm in diameter, and some vesicles develop pustular apices.” [Zacherle & Silver 1982 p192]

During this so-to-speak cretaceous era in the history of hot tub pathology, hot tub folliculitis came to be associated mainly if not exclusively with P.aeruginosa, so much so that the terms ‘Pseudomonas folliculitis’ and ‘hot tub folliculitis’ became and to some extent remain interchangeable. See e.g. Zacherle & Silver [1982]. A number of different P.aeruginosa serotypes have been associated with folliculitis outbreaks, with serotype 0.11 identified by Ratnam et al [ibid.] as the

“single most common etiological agent of recreationally associated folliculitis, accounting for more than half the number of outbreaks”.

Similar assertions are repeated by Charles B Toner, MD et al [2020], who advocate the antibiotic ciprofloxacin for recalcitrant cases; and also in MMWR [1982], which however relates a serotype 0.10 outbreak, including four cases of severe hemorrhagic ear infection and one case of chest cellulitis, amongst a group of students in North Carolina who partook of a session in a mobile redwood hot tub.

Nor are these the only hot tub-linked non-folliculitis syndromes with which serotypes of P.aeruginosa have been associated as the etiological agents. For instance, Crnich et al [2003] and Huhulescu et al [2011] report separate cases of P.aeruginosa pneumonia; these concern, respectively, a forty year old Wisconsin man infected by his own hot tub who survived, and an Austrian woman infected by a hot tub in a wellness clinic who died of septic multi-organ failure. In the former case, the involvement of the hot tub as the source was proved when the patient’s family brought in the filter, tests on which established the presence of a P.aeruginosa species matching a culture grown from the patient’s sputum. For a further report of Pseudomonas pneumonia implicating a hot tub, see Rose et al [1983]

Unlike the Pseudomonas/hot tub otitis, cellulitis and pneumonia cases just described, the folliculitis cases alluded to earlier have been regarded by most experts as being at the less severe end of the scale. Cases are mostly described as resolving themselves within a week or two if the victim can be prevailed upon to resist the urge to scratch, although otherwise treatment becomes “more difficult” [ibid].

In 2008, there was the first report of a more severe hot tub folliculitis case, in relation to which Aeromonas hydrophila rather than P.aeruginosa is thought to have been the etiological agent [sc. Mulholland & Yong-Gee 2008; as discussed below]. A.hydrophila is described as a gram-negative, rod-shaped bacterium, which is motile by means of a polar flagellum and is known to be common in both brackish and standing water and in soil. Historically speaking, the taxonomy of the Aeromonas genus to which A.hydrophila belongs has been the source of a certain amount of controversy. See in particular Joseph & Carnahan [2000], also both papers by Janda & Abbott [see below].

The status of A.hydrophila as a pathogen results from its propensity upon entering its host to make its way via the bloodstream to the first major organ it finds, where it settles down and starts producing toxins such as Aerolysin Cytotoxic Enterotoxin (ACT). ACT and other toxins associated with A.hydrophila destroy tissue, and can manifest in a variety of ways, mainly depending on the site of infection, but also on the nature of the patient’s comorbidities.

The specificities of the relationships in various historical cases between Aeromonas infection, site of infection and comorbidity, are explained comprehensively and clearly in two papers by Janda & Abbott [1998, 2010], which are more generally to be considered as valuable resources for students of that most recondite of disciplines, the history of A.hydrophila as an human pathogen. In particular, consider their table 1 [1998 p333], which consists in a list of significant events in the history thereof, and which is reproduced in its essentials below.

Janda & Abbott list the following syndromes with which Aeromonads in general have been at least tentatively associated:-

• Gastroenteritis [2010 pp47-50]. As Janda & Abbott remark,

“aeromonads are not universally accepted as gastrointestinal pathogens … Probably the largest single impediment to unquestionably establishing Aeromonas as a true gastrointestinal pathogen is the failure to identify a single clonally related outbreak of [diarrhoea] caused by this agent.” [ibid. p47]

Suspected outbreaks, principally involving sea-foods, have mostly involved “exceedingly short” incubation periods, which is not typical of Aeromonas [Edberg et al 2007]. Moreover, a second impediment has been the non-fulfillment of the Henle-Koch postulates, described as

“the prerequisites for experimentally establishing that a specific microorganism causes a particular disease”. [Mosby 2009].

The postulates in question [per McGraw-Hill 2002]:-

1. The agent must be present in all cases of the disease

2. The agent must be isolated from someone with the disease and grown in pure culture

3. Inoculation into a susceptible organism of the agent–from a pure culture—must produce the disease

4. The agent must be recovered from the infected–inoculated organism and grown again in culture.

Janda & Abbott note that the above data are based on their [1998]’s citations [2–9], to which, in order to avoid further tiresome duplication, the reader is directed.

In particular, postulate 3 has not been satisfied, since

“No animal model has ever been established that can faithfully reproduce the Aeromonas-associated diarrheal syndrome” [Janda & Abbott ibid. p48].

• Bacteremia/septicemia [Janda & Abbott ibid. pp50-52] In contrast to the situation vis à vis gastroenteritis, aeromonads are widely accepted as a source of blood-borne infection, there being some 300 citations attesting to this on Medline alone [ibid. p50]. According to Janda & Abbott [ibid.], immunocompromised people account for the vast majority (>80%) of Aeromonas septicemia cases, while middle-aged men with hepato-biliary diseases such as cirrhosis account for the majority of cases involving immunocompromise, although there have also been some cases amongst people suffering from myeloproliferative disorders. The residue of cases, in descending order of frequency, is comprised of trauma patients – commonly involving crush, burn, or penetrating wound injuries, or near-drowning incidents – healthy people in whom the etiology is not indicated, and reconstructive surgery patients.

surgery patients.

• Skin/soft tissue infections (ssti’s) [pp52-53]. Aeromonas ssti’s manifest with varying degrees of severity:-
• Mild cases:- “topical problems such as pustular lesions” [p52]
• Intermediate cases:- subcutaneous infections, i.e. cellulitis.
• Severe cases:- subcutaneous infections spreading along fascial planes, i.e. necrotizing fasciitis, potentially involving severe damage to muscle tissue, i.e. myonecrosis.

Again, the severest cases tend to be seen amongst people with liver disease and cancer patients. Necrotizing fasciitis and myonecrosis are associated with high mortality rates (60-75%), favourable outcomes only being secured by early correct diagnosis and appropriate treatment – debridement, irrigation, antibiotics.

More than two thirds of Aeromonas ssti’s arise either from “traumatic occupational injuries” [p53] or from exposures via sporting or recreational injuries. The leading authority on the subject of Aeromonas infections acquired by this route is probably Amy Horneman (formerly Martin-Carnahan). In particular, her co-authored Joseph & Carnahan [2000] is recognized as a seminal publication in the field. To quote the L.A Times [q.v. previous f.n.],

“Horneman has spent 30 years studying Aeromonas hydrophila, making it the focus of her research and studies for her master’s and doctoral degrees. She attends international medical meetings to alert fellow medical experts about its dangers, and cures. She helped sequence the bacterium’s DNA in published 2006 medical papers, and has been tapped for decades to write an annual update on Aeromonas hydrophila that is used to bring medical doctors around the world up to speed on the latest data.”

Horneman herself memorably describes A.hydrophila as

“the Rodney Dangerfield of pathogens – doctors just don’t think of it.” [ibid.]

A propos of present proceedings, the first report implicating a hot tub as the source of an Aeromonas infection [Mulholland & Yong-Gee 2008] describes the oedema and pubic folliculitis suffered by a thirty-something couple from Brisbane; and features some particularly unsparing colour photographs of the male patient’s genitals, although judging by appearance and description this qualifies as an intermediate case. However, the Mulholland & Yong-Gee report requires a caveat, as the title of their paper suggests (“A possible case of …” [my itals.]), insofar as the involvement of the hot tub as the source of the infection is not proven. A.hydrophila can certainly be accepted as the etiological agent, since a bacterial culture of the male patient’s follicular pus grew a colony thereof; whereupon ciprofloxacin was prescribed in accordance with usual practice – see earlier fn. However, a culture of the water from the hot tub only

“grew mixed coliforms and Pseudomonas species”,

although the authors also note that

“the microbiology department advised that isolation of Aeromonas species from a small sample of contaminated water was very unlikely to be positive even if the bacteria were present.” [ibid. p40]

That is to say, although this certainly seems to be a case of Aeromonas folliculitis, there is no direct evidence of the hot tub being the source of the two infections.

• Intra-abdominal infections (iai’s) [Janda & Abbott ibid. pp53-54]. iai’s are defined as infections which “spread beyond the hollow viscus of origin” [p53] into the peritoneal space, and include peritonitis, pancreatitis, acute cholangitis, and hepatic abscess. Peritonitis is distinguished into a relatively rare primary form, in which the infection is bacteremic, and a relatively common secondary form, where the infection is of biliary or gastrointestinal provenance. Janda & Abbott state that Aeromonas iai’s are a particular problem in South-East Asia [p54], most commonly found, again, in middle-aged men with underlying medical conditions, viz., presumably, illnesses of the kinds specified just above.
• Respiratory tract infections [pp54-55]. In the past, Aeromonads isolated in the sputum of patients have tended to be apprehended as transitory colonizations, and reports identifying Aeromonas as a pulmonary pathogen have been few and far between. Latterly however, Aeromonas has been associated with an increasing number of cases, predominantly of pneumonia but also of other pulmonary diseases, arising principally from a variety of near-drowning events. A peculiar feature of this mode of infection is that it often involves exceedingly rapid deterioration – Janda & Abbott quote 50% mortality within four to 48 hours following hospital admission.
• Urogenital tract infections (uti’s) [p55]. Janda & Abbott observe that Aeromonas uti’s have to date received “only cursory attention in published studies. The four cases which they do report all concern male patients with underlying conditions, viz:-
• A 69 year old diabetic also suffering from chronic hepatitis, who developed necrotizing fasciitis following an initially successful treatment for his initial Aeromonas uti. [Hsueh et al 1998]
• A 13 year old with congenital spina bifida, apparently infected by a replacement catheter. [Hua et al 2004]
• An otherwise healthy 39 year old with a two month history of uti presenting symptoms, for which A caviae was identified as the etiological agent, although no source was found for his infection. [Al-Benwan et al 2007]
• A 39 year old alcoholic with a fatty liver who developed Aeromonas prostatitis. No source was found, leaving the authors to speculate that it was all because he was fucking working class and given to wallowing in filth. [Huang et al 2007]
• Eye infections [p55]. Janda and Abbott direct the reader to various reports of endophthalmitis, keratitis and corneal ulceration, in which contact lenses are implicated.