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.