**7.6 Does the use of antimicrobial devices increase the risk of resistant infections?**

Concern has been expressed that antimicrobial shunt and EVD catheters might give rise to increased antimicrobial resistance. This has been investigated in vitro [91]. A central venous catheter impregnated in the same way and with the same antimicrobials as the rifampicin-minocycline EVD was serially exposed to bacteria in vitro for 21 days without any resistance, again due to the Dual Drug Principle. These in vitro findings confirmed an earlier study by Munson et al. [92] A clinical study of the rifampicin-clindamycin shunt showed that the overall infection rate fell and there was no increase in gram negative bacteria following its use [93]. However, in a systematic review of rifampicin-minocycline and rifampicin-clindamycin impregnated shunts and EVDs it was claimed that the use of these devices ran the risk of increase in more virulent and drug-resistant infections [79]. The evidence for this, cited by the authors, was a large study of over 2000 paediatric shunt placements using either plain catheters or the rifampicin-clindamycin shunts [94]. The authors found a statistically significant reduction in infection in the antimicrobial shunt group (p < 0.005). They also noted a change in the proportions of shunt pathogens. The proportions of *S aureus* infection in each group were approximately the same, whereas the proportions of *S epidermidis* infections fell from 52 to 16% in the

#### *Infections in Intracranial Pressure Management: Impact of New Technologies on Infection Rates DOI: http://dx.doi.org/10.5772/intechopen.110349*

antimicrobial shunt group. Moreover, the proportions of shunt infections due to gram negative bacilli were identical. The authors stated that no unusually resistant bacteria were isolated in either group. The only significant change was the rate of *C acnes* infection: 2.2% in the control group and 16% in the antimicrobial shunt group. This was a sequential study with a historical control group, and the authors considered that the apparent proportional increase in *C acnes* infections was due to the introduction during the period that the antimicrobial shunt was used of extended culture times, which are essential for isolation of this organism. The statement by Konstantelias et al. [79] is therefore based on a misunderstanding of the source data cited. Increased rifampicin resistance was claimed to be due to the use of rifampicinclindamycin impregnated shunts [95]. This study concerned the consecutive use of these shunts in all cases for 52 months, during which there were only 4 shunt infections (3.2%), all due to rifampicin—resistant *S epidermidis*. The authors felt that this had revealed a threat of selection of rifampicin resistance due to the use of these shunts. However, 4 shunt infections in 4.3 years equates to a shunt infection rate of 0.92%. Also, it is recognised that a very small proportion of *S epidermidis* strains are resistant to rifampicin, and an encounter with such a resistant strain by a patient with a rifampicin—impregnated shunt would be as likely to result in a shunt infection as if a plain catheter were used. There was no evidence in this study that the use of rifampicin-impregnated shunts had caused the rifampicin resistance.

Bacterial resistance due to drug exposure can arise in other ways than genetic mutation. One important example is the consequence of antibiotic exposure in "normal flora" sites such as the skin, intestine or mucous membranes. Here the maintenance of the balance of many different bacteria and fungi is important. The commensal bacteria at these sites are largely beneficial, but if the balance is disturbed so that one organism is allowed to predominate, then a disease state can result. A common example of this is the overgrowth of *Candida albicans*, a commensal yeast, that is a cause of thrush after a course of antibiotics. In the context of EVD management, prophylactic antibiotics are used either as one dose at insertion, or continued systemic administration throughout the use of EVD. These two regimens have been considered in terms of their potential to reduce EVD infection. A study of antibiotic prophylaxis for 24 hr. compared to an extended regimen for the duration of EVD found no significant difference in EVD infection but there was a statistically significant fall in the number of cases of *Clostridioides difficile* infection in patients with EVD [96]. *C difficil*e can cause life-threatening colitis that may require colectomy. The bacterium is a normal commensal of the colon in small numbers, but if the ecological balance of the colonic microbiome is disturbed by antibiotics, *C difficile* numbers rise and the toxin produced causes necrosis of the colonic epithelium and severe inflammation. Another study has confirmed this, with statistically significant falls in both *C difficile* infection and antibiotic use [26]. A similar result has been reported in the context of intracranial pressure monitoring, where there was difference in infection (0.7 vs. 1.4 per patient, (p = 0.05) and particularly in the number of multidrug resistant bacteria isolated per patient (0.03 vs. 0.33. p < 0.01) indicating no advantage in extended prophylaxis but a significant increase in infections due to resistant bacteria. This pattern was also seen in the ventilator-associated pneumonia (VAP) and septicaemia cases [97]. Prolonged antibiotic use has also been identified as a key factor in the increase in *A baumannii* infections in ventilated trauma patients [98]. Others have now questioned the use of extended duration antibiotic prophylaxis for EVD, on the grounds of both lack of benefit and risk of drug resistant infections and *C difficile* disease.

### **7.7 Antimicrobial devices and antibiotic prophylaxis**

The role of antimicrobial EVD catheters in reducing the need for prophylactic antibiotics has also received attention. One sequential study compared ventriculitis rates between a group receiving a rifampicin+clindamycin EVD and single dose antibiotic prophylaxis with a second group that had extended antibiotics with plain EVD catheters. There was a non-statistically significant reduction in ventriculitis in the antimicrobial catheter group, indicating that the extended duration antibiotic regimen did not add any benefit over antimicrobial EVD catheters. However, an important finding was that there were 3 cases of serious *C difficile* disease in the group without antimicrobial catheters, one patient requiring a colectomy [27]. The authors concluded that the antimicrobial catheters were as effective in preventing EVD infections as extended antibiotic prophylaxis, but safer. Another sequential study with 545 EVD placements, all using the rifampicin+clindamycin catheter, showed that there was a statistically non-significant fall in ventriculitis rates after switch from extended antibiotic prophylaxis to single dose, but a statistically significant fall in nosocomial infections such as VAP. The authors concluded that there was no need for an extended prophylaxis regimen if antimicrobial EVD catheters were used [99].
