A necessary step in developing SSIs is microbial contamination of the surgical wound. The risk of developing an SSI is related to the amount of microbial contamination along with the virulence of the organism against the various host defenses. Surgical wounds contaminated with >10⁵ microorganisms per gram of tissue increase the risk of developing an SSI [27]. The amount of microbial contamination needed to cause an infection is reduced with the presence of a foreign body in the wound [28]. Devitalized tissue likely has the same effect. Virulence factors contribute to microbial infection through a variety of mechanisms. Microorganisms may procedure substances, such as toxins, that contribute to its survival within a host or aid in the destruction of the host’s environment [25]. For example, gram-negative bacteria produce endotoxins which stimulate cytokine production that initiate the systemic inflammatory response syndrome cascade [29]. Other bacteria have surface components that inhibit phagocytosis and facilitate microbial invasion. Gram-positive bacteria ­produce substances that interfere with a host’s natural phagocytic defenses [30].

Most microbial invasion leading to SSIs involve endogenous flora from the patient’s skin, mucous membranes, or hollow viscera. Skin and mucous membrane flora are typically aerobic gram-positive cocci (e.g., staphylococci), whereas anaerobic and gram-negative aerobes predominate in fecal flora [31]. Another source of pathogens can be exogenous from the operating room environment (e.g., personnel, instruments), and these microbes are typically gram-positive aerobes but can also include fungal elements [32, 33].

Host factors are also important in the pathogenesis of SSIs. Table 18.2 lists patient and operation factors that may increase the risk of SSI [18, 23, 25]. The patient factors weaken the host defenses or increase the amount and/or spectrum of microbes at the operative site. The surgical factors increase the likelihood that microbes can proliferate at the operative site. There are some additional factors that specifically increase risk of postoperative UTI, including anatomic anomalies of the urinary tract and externalized urinary catheters [34].

An antimicrobial prophylaxis program should ensure that the benefits of prophylaxis outweigh the risks. There are several ways in which antibiotic administration can harm. Allergic reactions can occur, which range from minor cutaneous events (e.g., rashes) to life-threatening reactions (e.g., anaphylaxis). Suppression of normal bacterial flora can lead to fungal infection, Clostridium difficile colitis, colonization, and other adverse events [35]. C. difficile infections (CDI) have typically been associated with clindamycin, third-generation cephalosporins, penicillins, and more recently, fluoroquinolones [36]. The incidence of CDI is rising and the economic cost annually is over $3 billion [37]. In addition, C. difficile is demonstrating increasing resistance to the typical treatment with oral metronidazole or vancomycin [36]. Finally, antibiotic administration can lead to selection of resistant microbes; the overuse and misuse of antibiotics is partially the cause of the worldwide increase in microbial resistance [38]. For example, the incidence of methicillin resistant Staphylococcus aureus in US hospitals is now greater than 55% [23]. A recent study that evaluated over 10,000 urine cultures noted resistance of Escherichia coli to fluoroquinolones in 25% and to trimethoprim/sulfamethoxazole in 30% [34]. Limiting and controlling the use of antibiotics should reduce the problem of resistance. Given these potentially very serious direct and indirect adverse effects of antimicrobial prophylaxis, it is clear that appropriate antimicrobial prophylaxis is indication-specific and of a limited duration [35].

Antibiotic regimens for prophylaxis entail administrating an antimicrobial agent before, and possibly for a limited time following, the procedure to prevent a postprocedural infection [34]. The agent should be targeted against disease-specific bacterial flora within the region of the operative field. It should be of a limited duration, to reduce cost, toxicity, and antimicrobial resistance [39]. The agent should obtain appropriate tissue and serum levels that exceed the minimum inhibitory concentration for organisms in the intended operative site. If possible, the drugs half-live should be such to maintain sufficient tissue concentration levels during the procedure without the need for additional doses [35]. Therefore the timing and dosing of antimicrobial prophylaxis are important for optimal drug-tissue concentrations during the procedure. Infusion of the first dose should be within 60 min of surgical incision, except for intravenous fluoroquinolones and vancomycin, which should be within 120 min [22]. The agent should be re-administered at one to two half-lives for prolonged procedures [18]. For the majority of procedures, the literature suggests a single dose prophylaxis or discontinuation within 24 h from the end of the procedure [25]. Some instances where antimicrobial prophylaxis may be extended include a preexisting infection, placement of prosthetic material or manipulation of an indwelling tube [35].

There are very few randomized controlled trials (RCTs) available to inform the specific antimicrobial prophylaxis regimen for genitourinary surgery. Currently, the best strategy is for urologists to familiarize themselves with the American Urological Association’s (AUA) Best Practice Policy Statement on Urologic Surgery Antimicrobial Prophylaxis, in addition to consulting hospital antibiotic policies and local drug resistant patterns, to aid in the selection of a specific antimicrobial prophylaxis program [35].

Specifically for the genitourinary tract, fluoroquinolones, cephalosporins, and aminoglycosides have been advocated for prophylaxis due to their long half-lives, antimicrobial activity against the common encountered pathogens, minimal adverse reactions, and low cost [35, 39]. A review of the literature regarding antimicrobial prophylaxis typically involves trials within other surgical specialties outside of urology. While cephalosporins and aminoglycosides have been well established for SSI prophylaxis in general, fluoroquinolones are more particular to urological procedures. RCTs involving endourologic procedures have confirmed the efficacy and low cost of oral fluoroquinolones for antimicrobial prophylaxis for these procedures [40, 41].

The AUA recommendations cite level Ib evidence (evidence obtained from at least one RCT) as supporting antimicrobial prophylaxis during all types of ureteroscopic procedures [35]. The recommended agents include fluoroqui­nolone, trimethoprim–sulfamethoxazole (TMP-SMX), aminoglycoside  ±  ampicillin, first/second generation cephalosporin, or amoxicillin/­clavulanate. Knopf et al. [42] in 2003 performed a RCT comparing perioperative single oral dose fluoroquinolone to placebo in patients undergoing ureteroscopic stone removal. The treatment arm had a bacteriuria rate of 2% versus 13% for the placebo group. Another RCT did not reveal any difference in bacteriuria rates between single dose oral fluoroquinolone or intravenous cephalosporins for ureteroscopic procedures or ureteral stenting [40]. A small RCT comparing a single intravenous dose of cefotaxime to placebo during upper tract ureteroscopy or percutaneous renal surgery revealed a treatment arm bacteriuria rate of 5% compared to 12% for placebo [43]. Aghamir and associates [44] performed an RCT in 114 patients, comparing semirigid ureteroscopy with pneumatic lithotripsy with and without perioperative administration of intravenous cefazolin, and found that the incidence of bacteriuria was significantly reduced in the group receiving antimicrobial prophylaxis, although the incidence of symptomatic UTI did not differ between groups. In a smaller retrospective review, use of antimicrobial prophylaxis was associated with a reduced admission rate following intended outpatient ureteroscopy [45]. Ureteroscopic procedures without antimicrobial prophylaxis have been associated with UTI rates as high as 25% [46].

The European Association of Urology (EAU) guidelines on urologic infections differentiate between various ureteroscopic procedures [47]. For diagnostic ureteroscopy or distal ureteral calculi manipulation, the EAU guidelines do not recommend prophylactic antibiotics. However, for proximal or impacted stones antimicrobial prophylaxis is recommended. The EAU guidelines also incorporate risk factors such as size of stone, length of procedure, bleeding, and surgeon experience into the consideration for an antibiotic regimen.

Adherence to either the AUA or the EAU recommendations is poor, however, with the primary infraction being excessively prolonged course of antibiotics after ureteroscopy. A survey of members of the Endourological Society revealed that only 30% complied with the AUA recommendations about antimicrobial prophylaxis for ureteroscopy [48]. In a follow-up study, the survey was repeated 1 month after an email notification that summarized the AUA recommendations; the compliance rate improved to only 40% [49].

As noted above, hospital antibiotic policies and local drug resistant patterns are an important adjunct to published recommendations for choosing an antimicrobial prophylaxis regimen. At the authors’ institution, oral fluoroquinolones had been used for years as the perioperative antimicrobial prophylaxis for ureteroscopy, but in 2008 the preferred agent was changed to oral TMP-SMX owing to an increase in resistance of local E. coli urinary isolates to fluoroquinolones. In 2011, the preferred agent was changed again, to intravenous cefazolin, since sensitivity patterns had altered to the point that resistance to both fluoroquinolones and TMP-SMX was greater than to cefazolin.