Discussion
The incidence of CIED infections have increased almost 96% between 1993
to 2008 and the incidence of device infections has increased
proportionally as well8. The incidence of pocket
infections without blood stream infections was noted to be 1.37 per 1000
devices and defibrillators were associated with an increased risk when
compared to pacemakers9. This may be related to larger
sizes of the cardiac resynchronization devices and longer duration of
surgery which may contribute to infection. In the modern era, cosmetic
procedures, tattooing and pedicures account for more mycobacterial
infections when compared to surgical site procedures.
The most common predisposing factor for device-related endocarditis is
the presence of pocket infection1 and that is why
controlling the rate of pocket infection becomes crucial. Pocket
infections can also complicate and cause cutaneous erosion of the
generators and the bacteria may translocate from the pocket infection
through the electrodes. The risk factors for these infections include
immunocompromised status, diabetes mellitus and chronic renal
insufficiency10
Gram positive bacteria are the predominant causative pathogens, both
early (<1 year from device implantation) and late-onset
infection. Coagulase-negative staphylococci and Staphylococcus
aureus remain the most common pathogens, they account for 70% of the
infections11. Gram negative pathogens account for
6-9% of infections3. Rapidly growing mycobacteria are
common environmental organisms which have been isolated from soil, food,
natural water, various plants/animal surfaces and hospital
surfaces2. The species of RGM capable of affecting
humans consist primarily of the Mycobacterium fortuitum group,
the M. chelonae/abscessus group, and the M. smegmatisgroup2. They are known for presence of fatty acids
known as mycolic acids and they can produce visible colonies within 7
days of growth on solid medium4. Among the various
species, most commonly encountered RGM species are M. fortuitumand M. abscessus/M. chelonae 10.
Our case highlights the challenges in treating a pocket infection that
can be caused by a RGM such as M.fortuitum . Majority of the
infections occur <6 months after implantation, and our patient
was one of them. M. fortuitum usually takes >= 5
days to appear on the standard medium, exceeding the incubation time of
routine cultures leading to a missed opportunity for a diagnosis. Even
when growth is observed, these organisms appear as gram positive bacilli
on gram stain, and can be misinterpreted as a contaminant orCorynebacterium or Nocardia species5,12
Although these bacteria grow within 3-7 days on standard agar blood
culture media, cultures may not yield these mycobacteria since they may
not be held long enough to demonstrate the growth. Swab samples from
wounds maybe difficult to culture, some authors have suggested the use
of skin punch biopsies to capture these organisms. Presence of acid-fast
bacilli on smears may aid in the diagnosis. Accurate diagnosis requires
PCR-restriction enzyme analysis (PCR-REA)13. The
absence of constitutional symptoms such as fever, chills, rigors further
complicates the difficulty in diagnosing these infections.
Although recent evidence suggests the use of an antibacterial envelope
containing rifampin and minocycline to mitigate major infections, this
may not be effective against NTM infections . These infections do
not respond to the common anti-tuberculous drugs as well. These require
a prolonged course of treatment and even wound debridement to eliminate
these infections13. Identification of the sub-species
is important since they have predictable antimicrobial susceptibility
patterns14. M. fortuitum is generally more drug
susceptible when compared to the other species and often oral regimens
can be devised. Therapy with tetracyclines, sulfamethoxazole, and
quinolones is usually effective14. However, RGM can
develop macrolide resistance by mutations in the peptidyltransferase
region of the 23S ribosome gene15. Some experts opine
that macrolide should not be used in empiric therapy. However, good
results have been obtained when macrolides are combined with one other
additional drug if they demonstrate in-vitro
susceptibility14. A variety of drug combinations have
been used that includes ofloxacin, clarithromycin, amikacin,
sulfonamides, ciprofloxacin, doxycycline, and linezolid to deal with
these infections13,15. The duration of treatment
ranges from 3 months to longer durations. Pulmonary infections require a
more prolonged treatment course, sometimes upto a year. More often than
not, with these infections, it is strongly recommended that entire
device or hardware be removed urgently. An incomplete removal of the
device may result in higher relapse rates. The American Heart
Association statement recommend complete removal of all hardware (Class
1 evidence) from patients, even in the absence of systemic infections
signs10. Usually the recommendation is for
implantation of the CIED on the contralateral side. The optimal interval
between device replacement after removal is not defined and is dependent
on the extent of infection. Attempts to reuse the
pacemaker/defibrillators have resulted in infections even on the
contralateral side16. Moreover, the usual methods of
operating room sterilization are not sufficient for eradicating
mycobacteria.
For soft tissue infections due to M. fortuitum , a minimum of 4
months of therapy with at least two agents with in vitro activity
against the clinical isolate is necessary to provide a high likelihood
of cure. A longer duration of treatment generally is required because of
the propensity of the organism to cause a biofilm. Our patient was
treated with levofloxacin and Bactrim for 4 months. It is important to
monitor for adverse reactions of antibiotics since they are required for
longer duration.
In conclusion, CIED pocket infections caused by M. fortuituminfections are rare, often misinterpreted at the time of diagnosis. Once
diagnosed, combination therapy is better to avoid treatment failure due
to development of drug resistance when compared to monotherapy. Removal
of the entire device is recommended.