Surgical cutaneous infections span the spectrum of the superficial skin abscesses such as furuncles and carbuncles to the devastating and often fatal necrotizing deeper soft tissue infections.
A furuncle (boil) is a superficial skin abscess usually caused by S aureus infection at the level of the hair follicle. Bacteria asymptomatically inhabit most hair follicles, but it is thought that obstruction of the pilosebaceous apparatus is the triggering event for the formation of furuncles.
Some of the identified risk factors include puberty, male gender, obesity, diabetes, poor hygiene, as well as living in weathers characterized by a high level of humidity.
Even though staphylococci are the most common causative organisms, streptococci, gram-negative organisms, and anaerobic diphtheroids can also cause furuncles.
Furuncles present as itchy indurated small abscesses, surrounded by skin erythema. A small white area of skin necrosis is often notable at the top of the abscess.
Most furuncles resolve spontaneously, although larger lesions require incision and drainage. The use of antibiotics following incision and drainage is not routinely needed and is controversial. We recommend antibiotics only in the presence of concomitant extensive surrounding cellulitis. When antibiotics are prescribed, they should be stopped with resolution of the local and systemic symptoms. Antibacterial soap showers might be helpful in both treatment and prevention of recurrence.
Carbuncles are rare and result when several furuncles coalesce, extend to the subcutaneous tissue, and/or form a “network” of multilocular interconnected abscesses and tracts.
Carbuncles on the back of the neck are seen almost exclusively in diabetic or relatively immunocompromised patients. In addition to obesity and diabetes, chronic steroid intake and malnutrition are potential risk factors for carbuncles.
Similar to furuncles, S aureus remains the most common organism involved in carbuncles.
Carbuncles often have the appearance of multiple large furuncles with several openings draining pus. As carbuncles enlarge, the blood supply to the skin is destroyed and the tissue over the top of the abscess becomes white in color and necrotic in appearance. Patients might show some systemic signs such as fever and malaise.
Carbuncles often require incision and drainage; occasionally, a more extensive excision is required. When appropriate, the excision is continued until the many associated deep sinus tracts are removed. Antibiotics are usually needed in view of the associated extensive skin cellulitis and induration.
Hidradenitis suppurativa is a serious skin condition characterized by blockage and infection of the apocrine sweat glands. Hidradenitis most commonly involves the axilla or the groin. Since apocrine glands develop postpuberty, prepubertal disease is very rare. Even though hidradenitis often becomes chronic with serious patient morbidity and disability, systemic complications, and constitutional signs and symptoms are uncommon.
Obesity, puberty, female gender, and smoking are some of the identified risk factors associated with hidradenitis.
Hidradenitis is a polymicrobial infection involving gram-positive, gram-negative, and anaerobic organisms. Superinfection with fungal organisms is not uncommon, especially in the patient with chronic or recurrent hidradenitis.
Hidradenitis can affect any area where apocrine glands exist, most commonly the axilla and groin, but also the perineum, inframammary folds, gluteal folds, areola, and scrotum. On examination, erythematous tender skin nodules characterize early stages. This can quickly progress to deeper indurated abscesses with interconnected sinuses, purulent drainage, and associated regional lymphadenopathy.
Drainage of the individual abscesses and their associated sinuses is needed. If healing is delayed, fungal super-infections should be suspected and, if confirmed, should be treated as well. With chronic and recurrent infections, the involved skin and apocrine glands can be excised, and the underlying soft tissue left to heal by secondary intention. Skin flaps and grafts might be needed in later stages, as the resultant scarring can be severe. Topical clindamycin, systemic tetracycline, and isotretinoin are potential adjunctive therapies. Weight loss and hygiene-focused interventions should be encouraged to decrease the risk of recurrence.
NECROTIZING SKIN & SKIN STRUCTURE INFECTIONS
Accurate data on the incidence of necrotizing skin and skin structure infections (NSSSIs) is lacking, and most existing data are based on single institutions’ experiences, suggesting a large variability in clinical presentation, severity as well as outcome. NSSSIs are skin and soft tissue infections characterized by widespread and severe tissue necrosis resulting from aggressive and life-threatening bacteria that are often able to secrete toxins. NSSSIs are also known as gas gangrene, necrotizing fasciitis (when involving fascial layers), Fournier gangrene (when involving the perineum and genitalia), and Ludwig angina (when involving the floor of the mouth).
NSSSIs can be caused by single agents such as clostridia or streptococci species, but most are polymicrobial in etiology. An inciting site (eg, puncture wound, insect bite) can occasionally be discovered by history or physical examination. In the perineum, manipulation of the urogenital tract and diabetes are known to be associated with NSSTI. The infection is classically one of sudden onset and rapid progression through ischemic tissue planes, occasionally with air formation at deeper layers. Small vessel thrombosis occurs along the infection progression pathway, and thus, the underlying deeper tissue damage is almost always much more pronounced than what the overlying skin appearance suggests.
By definition, type I NSSSIs are polymicrobial (eg, streptococci, clostridia), while type II NSSSIs are monomicrobial. C perfringens secretes exotoxins (eg, lecithinases, collagenases, proteases, hemolysins) that lead to small vessel thrombosis and allow for rapid progression and aggressive invasion of fascial and muscle planes. These toxins contribute to the serious deep tissue destruction and the overlying skin grayish discoloration. The alpha toxin (a lecithinase) is believed to be an essential contributor to clostridial virulence. In addition to their local effect, these toxins may lead to severe sepsis, pronounced SIRS, and not uncommonly MODS. Streptococci can also secrete several exotoxins with similar virulence leading to fascial and deeper plane disruptions. S pyogenes (group A strep), although rare, is classically described to secrete a superantigen toxin that can result in toxic shock syndrome with resultant organ failure. NSSSIs are often caused by mixed nonclostridial, nonstreptococcal bacteria, including staphylococci, gram negatives, and anaerobes.
Immunocompromised (eg, HIV, diabetes), intravenous drug abuse, and cancer patients are at a particularly higher risk of developing NSSSIs, as well as malnourished and obese patients.
Prompt suspicion and early diagnosis of NSSSIs are essential. In early stages, patients often have fever and pain out of proportion to physical examination findings. Erythema, induration, hemorrhagic skin bulla, blisters, and vesicles are occasionally present. Grayish discoloration of the underlying skin and pain beyond the affected skin area are especially suggestive of deeper underlying tissue involvement. “Dishwasher-like” gray discharge might be seen and should raise suspicion of NSSSIs. Patients can quickly develop systemic signs of toxicity with hypotension, tachycardia, electrolyte imbalances, lethargy, and even organ failure. Laboratory workup typically shows leukocytosis (with or without bandemia) or leucopenia, hyponatremia, and acidosis. Several models have been developed over the years in an attempt to predict the probability of a skin infection being a NSSTI versus a more benign superficial skin infection. The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score assigns different point scores to each of six laboratory values (Table 8–9). A LRINEC score of six or more was found in a study of 89 NSSSIs to have a positive predictive value of 92% and a negative predictive of 96% for NSSTI. Radiologically, plain films showing deep soft tissue air are pathognomonic. Computed tomography (CT) scan is the standard of care when difficulty arises in differentiating between “benign” skin or soft tissue infection and NSSSIs. CT images often show inflammation and edema at the deeper fascial or muscular layers, and occasionally will show gas between these tissue layers. Although crepitus as felt on physical examination and/or deep tissue air as diagnosed by plain radiography or CT imaging have been classically described with several (but not all) clostridial species, they may occur with nonclostridial infections as well. When the clinical picture and the radiological imaging fail to differentiate between benign soft tissue infection and NSSSIs, diagnostic surgical exploration of the area in question is needed. Operative findings suggestive of NSSSIs include pale and/or necrotic deep tissue, “dishwasher” nonpurulent gray discharge, nonbleeding soft tissue, and thrombosed microvessels. Easy separation with unopposed finger “sliding” between the tissue planes (the “finger test”) is highly suggestive of NSSSIs. Pathologic examination will reveal severe inflammation and tissue necrosis.
Table 8–9.The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) Score. ||Download (.pdf) Table 8–9. The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) Score.
|Variable ||Points |
|C-reactive protein (mg/L) > 150 ||4 |
WBC count (× 103 cells/mcL)
|Sodium (mmol/L) < 135 ||2 |
|Creatinine (μmol/L) > 141 ||2 |
|Glucose (mmol/L) > 10 ||1 |
A NSSSI is a surgical emergency and requires immediate
Wide surgical debridement
Hemodynamic and fluid resuscitation
Wide Surgical Debridement
All tissue that appears pale, ischemic, or necrotic, “lifts off” easily, or does not bleed appropriately needs to be removed. This should include the overlying skin, even when it appears viable, as studies have documented severe vasculitis and microvessel thrombosis that eventually lead to loss of skin, if not adequately debrided. Extensive debridement is usually needed, with one or more repeat trips to the operating room, until viable tissue is ensured. When an extremity is involved, amputation might be required, although attempts at debridement and limb salvage, with a planned “second look” are reasonable and might be preferred. Perirectal NSSSI and Fournier gangrene occasionally necessitate creation of an ostomy and/or urinary diversion. Depending on the extent and location of debridement, many patients, if they survive and recover, are disfigured and will need reconstructive surgery ranging from simple split thickness skin grafts to major flap reconstructions.
As soon as a NSSSI is suspected, broad-spectrum antibiotics should be initiated. Gram-positive, gram-negative, and anaerobic organisms need to be covered. A combination of a penicillin-based agent or cephalosporin with an aminoglycoside or fluoroquinolone and an anti-anaerobic agent (eg, metronidazole or clindamycin) is a reasonable starting empiric regimen. Clindamycin has been shown by in vitro studies to have anti-inflammatory and toxin-neutralizing effects, in addition to its antibacterial effects. If methicillin-resistant S aureus is suspected, penicillins can be replaced by vancomycin or linezolid. Aminoglycosides can be replaced by third- or fourth-generation cephalosporins (eg, cefepime, cefotaxime) or by carbapenems (eg, imipenem, meropenem, ertapenem), if indicated (eg, in patients with acute renal failure). The Infectious Diseases Society of America (IDSA) published guidelines for the antibiotic choices in NSSSIs are reported in Table 8–10.
Table 8–10.The Infectious Diseases Society of America guidelines for antibiotic treatment of NSSTIs. ||Download (.pdf) Table 8–10. The Infectious Diseases Society of America guidelines for antibiotic treatment of NSSTIs.
|First-Line Antimicrobial Agent, by Infection Type ||Adult Dosage ||Antimicrobial Agent(s) for Patients With Severe Penicillin Hypersensitivity |
|Mixed infection || || |
|1.5–3.0 g every 6–8 h iv ||Clindamycin or metronidazolea with an aminoglycoside or fluoroquinolone |
|3.37 g every 6–8 h iv || |
|600–900 mg/kg every 8 h iv || |
| ciprofloxacin ||400 mg every 12 h iv || |
| Imipenem/cilastatin ||1 g every 6–8 h iv ||… |
| Meropenem ||1 g every 8 h iv ||… |
| Ertapenem ||1 g every day iv ||… |
|2 g every 6 h iv ||… |
|500 mg every 6 h iv || |
| clindamycin ||600–900 mg/kg every 8 h iv || |
|Streptococcus infection || || |
|2–4 MU every 4–6 h iv (adults) ||Vancomycin, linezolid, quinupristin/dalfopristin, or daptomycin |
| clindamycin ||600–900 mg/kg every 8 h iv || |
|S aureus infection || || |
| Nafcillin ||1–2 g every 4 h iv ||Vancomycin, linezolid, quinupristin/dalfopristin, daptomycin |
| Oxacillin ||1–2 g every 4 h iv ||… |
| Cefazolin ||1 g every 8 h iv ||… |
| Vancomycin (for resistant strains) ||30 mg/kg/day in 2 divided doses iv ||… |
| Clindamycin ||600–900 mg/kg every 8 h iv ||Bacteriostatic; potential of cross-resistance and emergence of resistance in erythromycin-resistant strains; inducible resistance in methicillin-resistant S aureus |
|Clostridium infection || || |
| Clindamycin ||600–900 mg/kg every 8 h iv ||… |
| Penicillin ||2–4 MU every 4–6 h iv ||… |
The usefulness of hyperbaric oxygen in the treatment of NSSTI is controversial. Several small retrospective studies have suggested decreased mortality with hyperbaric therapy, but the absence of supportive level one evidence, combined with the logistical difficulties in critically ill patients remain the main obstacles to recommend its routine utilization.
NSSSI has a poor prognosis with reported mortality as high as 20%-50%, and an even higher morbidity rate. Diabetic patients and/or those presenting with septic shock and/or multisystem organ failure are at a particularly higher risk of mortality. Shorter time from onset of infection to operative debridement has been shown consistently to correlate with better survival.
Organ/space infections are often deep infections resulting from uncontrolled infection or perforation of an internal organ. Internal postoperative abscesses are termed organ/space SSIs, and have been discussed previously. In addition to antibiotic treatment, many of these organ/space infections will need drainage.
Intra-Abdominal Abscesses and Infections
In the era of high-resolution CT imaging, diseases like acute diverticulitis and acute perforated appendicitis are more likely to be successfully managed nonoperatively in the acute clinical setting. When patients have no signs of diffuse peritonitis, periappendiceal, pericolonic abscesses, and other contained intraperitoneal abscesses may be drained percutaneously under radiological guidance when accessible. With the combination of percutaneous drainage and adequate antibiotic coverage, patients’ intra-abdominal infections can be treated adequately, allowing for the inflammation to resolve with potentially one-stage and less complicated surgical intervention at a later time to address the diseased organ. When percutaneous drainage is not possible, usually because of the abscess location and its inaccessibility to radiological interventions, surgical drainage with removal of the infected organ (eg, appendectomy, colectomy) is warranted. If the abscess is less than 3-4 cm in diameter, an attempt at treatment with antibiotics alone without percutaneous or surgical drainage is a reasonable option in the stable patient without peritoneal signs. The management of complicated intra-abdominal infections, whether community acquired or health care associated, whether originating from the hepatobiliary system or the gastrointestinal system, is beyond the scope and goal of this chapter. The IDSA has recently published useful guidelines for diagnosis and treatment of intra-abdominal infections that emphasize
Source control (surgical or percutaneous drainage)
Early and appropriate antibiotics coverage
Microbiological evaluation, when feasible
These guidelines can be accessed at www.idsociety.org.
Empyema is a collection of pus in the pleural cavity, most commonly related to bacterial pneumonia and resulting parapneumonic effusions. Occasionally, empyemas occur postprocedurally, such as following thoracentesis, chest tube placement, or lung resection. When empyema occurs, drainage is needed. In addition to antibiotics, tube thoracostomy is the recommended initial management. Unfortunately, chest tubes lumens often get clogged with thick pus, leading to placement of additional tubes, and not infrequently, failure to completely drain the pleural cavity and re-expand the lung. When that occurs, surgical drainage with decortication using a video-assisted thoracoscopic approach or an open thoracotomy is indicated. In cases of recurrent or persistent empyema despite surgical management, creation of an Eloesser flap or window with an open track between the pleural cavity and the outside skin might be needed to allow adequate and definitive drainage of the empyema.
CLOSTRIDIUM DIFFICILE COLITIS
Clostridium difficile as an organism can be recovered in the feces of 5% of healthy individuals. The use of antibiotics can alter the colonic flora allowing for C difficile overgrowth and colonization of the colon. The result is C difficile colitis with severity ranging from simple watery diarrhea to life-threatening sepsis. C difficile is currently considered one of the most common and most serious health care–associated infections.
Antibiotic intake is the single most important risk factor for C difficile colitis and has been described even following a single antibiotic dose administration as with SSI prophylaxis. Although all antibiotics can be implicated, fluoroquinolones, clindamycin, penicillins, and cephalosporins are the most frequently encountered culprits, partly because of their widespread utilization. A Canadian study conducted during a relatively recent C difficile outbreak in Quebec strongly suggested that fluoroquinolones are currently the antibiotics most commonly associated with C difficile infections rather than clindamycin as classically and historically described. Table 8–11 lists the different antibiotics classified into those with high, moderate, and small risk of C difficile infection.
Table 8–11.Antibiotics associated with Clostridium difficile colitis. ||Download (.pdf) Table 8–11. Antibiotics associated with Clostridium difficile colitis.
Transmission of C difficile by health care providers caring for patients with C difficile colitis has resulted in outbreaks of C difficile among patients within hospitals and the emergence of multidrug-resistant organisms. These epidemics are addressed and prevented by proper hand hygiene among health care providers and the isolation of patients with C difficile colitis.
The presentation of C difficile colitis can range from the asymptomatic carrier state that requires no treatment, and the mild diarrhea state that can easily be treated with oral antibiotics as an outpatient, to the severely toxic, septic, and MODS patient presentation. Across all the severity range, watery diarrhea, and abdominal distention remain the sine-qua-non of C difficile colitis. Lower abdominal pain may also be present, and is usually of a crampy nonspecific nature. Constitutional symptoms such as fever and malaise are also frequently reported. The presence of peritoneal signs such as rebound tenderness or guarding may be indicative of colonic perforation (rare) or severe and/or fulminant C difficile colitis. Leukocytosis is often present and not infrequently elevated above 20K cells/mcL. In fact, it is not unreasonable to test the hospitalized patient with unclear etiology of leukocytosis for occult C difficile infection, even in the absence of diarrhea. In a small study of inpatients with white blood cell counts above 15K cells/mcL, and without a clear etiology of the leukocytosis, Wanahita et al found that 58% of the patients tested positive for C difficile. Fecal leukocytes are also often present, but nonspecific. On colonoscopy, when performed, patients with C difficile colitis frequently show mucosal ulcerations with the pathognomonic pseudomembranes, often described as raised yellow plaques composed of fibrinous exudates. Abdominal x-rays may show “thumb printing” suggestive of colonic inflammation, but are often nonspecific. CT examination of the abdomen shows thickening of the colonic wall. In fulminant C difficile colitis, the abdominal x-rays and CT may show toxic megacolon with a diffusely dilated colon.
In addition to the clinical patient presentation described above, diagnostic tests for C difficile currently consist of either C difficile organism detection (eg, anaerobic stool culture, antigen testing) or toxin A or B detection tools (eg, cytotoxin assays, enzyme immunoassays, or polymerase chain reaction [PCR] testing). The best approach to diagnose C difficile remains controversial and institution-dependent. The stool culture is a sensitive test, but has a long turnover time (2-3 days) that is suboptimal in the critically ill patient who needs a fast and accurate diagnosis. Antigen detection is a reasonable screening test, but needs further confirmation when positive. The most sensitive test (considered standard by many) is the cytotoxin assay. Its sensitivity is above 95%, and its specificity approaches 100%, but it is an expensive test with 24-48 hours turnover time.
Treatment of asymptomatic patients is not indicated. On the other hand, the clinical, laboratory, and radiological presentation of the patient might carry a sufficient suspicion for C difficile infection that empiric antibiotics are justified pending C difficile organism or toxin detection tests. For patients with mild disease, level 1 evidence suggests the safety and equivalency of single-agent oral antibiotic treatment with PO metronidazole (500 mg every 8 hours) or PO vancomycin (125 mg every 6 hours). PO vancomycin is not systemically absorbed and is thus wholly available in the colonic lumen where the C difficile infection exists. A 2-week course of either antibiotics is recommended. Patients might still test positive for C difficile for many weeks despite treatment, and therefore retesting these patients for C difficile when the antibiotic course is done and the patient’s signs and symptoms resolved, is not recommended. Adjunct therapies for C difficile such as probiotics, toxin-binding resins, and immunoglobulins have been used, but the evidence for their utility is still controversial.
Treatment of Severe C difficile Colitis
The definition of severe C difficile infection varies, but the IDSA 2010 guidelines define it as leukocytosis above 15K cells/mcL or a creatinine 1.5 times higher than the patient’s predisease baseline. For severe C difficile colitis, these same guidelines recommend PO vancomycin rather than metronidazole as a first-line agent. Combination therapy with PO vancomycin, intravenous metronidazole +/– vancomycin enemas might be indicated in case of failure of single-agent therapy. Vancomycin enemas are particularly useful in patients with ileus (questionable adequate intracolonic concentration from PO vancomycin alone), those with PO intolerance, and possibly those with severe distal colonic inflammation (rectosigmoid colon). Fidaxomicin (200 mg every 12 hours) is a relatively new bactericidal antibiotic with promising results as an alternative therapy. In a randomized clinical trial comparing fidaxomicin and vancomycin, the cure rates were equivalent. Patients with refractory severe C difficile colitis, those who progress to toxic megacolon, or those with hemodynamic instability or showing signs of early MODS should be considered for prompt surgical intervention. The timing and decision to operate are controversial, but there is certainly value in earlier intervention in critically ill patients, as the mortality of fulminant C difficile infection remains as high as 30%-50%. Independent predictors of mortality include age more than 70 years, leukocytosis more than 35K cells/mcL, leucopenia less than 4K cells/mcL, hemodynamic instability and respiratory failure. When surgery is indicated, the procedure of choice is a subtotal colectomy with end ileostomy. A single-center study has recently demonstrated improved outcomes in severe C difficile colitis using an alternative approach where a loop ileostomy is created and subsequent intraoperative colonic washout was performed with polyethelene glycol solution. In this small study of fewer than 50 patients, the new approach was associated with decreased mortality and more than 90% colon preservation, when compared to the traditional subtotal colectomy approach.
Antibiotic optimal management includes the following guiding principles:
Establishing a clinical diagnosis of infection and/or sepsis
Establishing an “evidence-based-guess” of the likely nature of the involved pathogen(s)
Attempting to obtain microbiological data (Gram stain and culture), when possible
Prompt initiation of broad-spectrum empiric antibiotics likely to cover the culprit pathogen(s)
Selectively narrowing the antibiotic regimen to cover the pathogen recovered in microbiological testing
The decisions to initiate, continue, or tailor the antibiotic choices for each patient should be carefully balanced against the increasingly serious challenge facing health care, namely, the epidemic emergence of multidrug-resistant organisms such as methicillin-resistant S aureus (MRSA), vancomycin-resistant Enterococcus (VRE), and multidrug-resistant gram-negative organisms.
EMPIRIC & PATHOGEN-DIRECTED ANTIBIOTIC SELECTION
Selecting the appropriate empiric antibiotics entails an understanding of the nature of the infectious process affecting the patient, the most likely organisms causing the infection, as well as awareness of the antibiotic resistance map at the local health care institution level. For example, simple skin infections are most likely caused by skin flora such as staphylococci and streptococci, and therefore an appropriate empiric treatment should at least cover gram-positive organisms. Acute diverticulitis with a pericolonic abscess is more likely to be caused by colonic flora, such as gram-negative and anaerobic bacteria, and therefore empiric treatment should focus on covering these pathogens. Once a specific organism has been recovered from the tested microbiological specimen, it is often possible to narrow the antibiotic regimen, even before the specific data on antibacterial susceptibilities is available using the microbiological properties of antibiotics and the currently available clinical experience. The use of local antibiograms is crucial and highly encouraged, as the patterns of bacterial susceptibilities and resistance vary not only from a region to the other but also from one institution to the other. Susceptibility testing methods include disk diffusion and dilution (broth microdilution, plates, and E-tests) procedures. Disk diffusion tests indicate whether a microbial culture is susceptible or resistant to serum-achievable, in vivo drug concentrations with conventional dosage regimens. In contrast, dilution procedures allow report of the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). The MIC is the lowest concentration of a specific antimicrobial agent that inhibits the test organism, while the MBC is the lowest concentration of a specific antimicrobial agent that kills the test organism. Tailoring therapy based on reported of susceptibility via disk diffusion or MIC is recommended.
Antibiotic Duration of Therapy
If all the sent cultures were found to be negative, and the suspicion for continuing infection is low, empiric antibiotics should be discontinued, as unnecessary antibiotic therapy clearly increases the risk of multidrug-resistant bacteria, C difficile colitis, and other side effects. The duration of antibiotic treatment depends on the nature of the infection and the severity of the clinical presentation. Treatment of acute uncomplicated infections should be continued at least until the patient is afebrile, the white blood cell count is normal, and the patient looks clinically well. Evidence-based guidelines for type of antibiotics and duration in the treatment of various infections have been developed and should be followed when possible. Most antibiotic regimens are now limited, although more difficult infections such as liver abscesses, brain abscesses, endocarditis, septic arthritis, or osteomyelitis require prolonged antibiotic therapy.
Failure of Clinical Response
Upon failure of clinical response to initial surgical intervention and antibiotic therapy, the clinician is encouraged to think of all the possible following explanations of failure of therapy:
The existence of another organism
The presence of an uncontrolled source of infection needing additional interventions
The presence of a concomitant super-infection (eg, with fungal organisms)
The development of a new drug resistance by the same isolated organism
Failure of the chosen antibiotic medication (despite favorable susceptibility data) to penetrate the site of infection
The latter may be due to the properties of the antibiotic itself, the chosen route of administration, or the specific physiology and morbidity of the patients themselves.
Antibiotics’ Side Effects
Adverse antibiotic reactions may occasionally mimic infection by causing fever, skin rashes, and mental status changes. Clinicians should consider this possibility in patients with persistent fevers despite appropriate antibiotic coverage and seeming resolution of the infectious process. In addition, antibiotics can result in microbial superinfections (eg, fungi, C difficile), emergence of new bacterial drug resistance, or organ toxicity.
Antibiotics in Renal or Hepatic Failure
Several antibiotics may induce or exacerbate existing organ dysfunction, most commonly renal or hepatic, and thus require intermittent assessment of kidney and liver function. Aminoglycosides and renal failure is a classic example.
In addition, decreased creatinine clearance at baseline or due to critical illness has an important influence on antimicrobial drug dosage, since most of these drugs are excreted, at least partially, by the kidneys. Therefore, many of these medications, such as vancomycin, penicillins, and aminoglycosides require adjustments in dosage or frequency of administration in the presence of renal insufficiency to prevent toxicity. Table 8–12 provides practical guidance into adjusting diverse antibiotic dosage and frequency for patients with hepatic or renal insufficiency, although additional assistance from the pharmacy department in these cases is universally advisable.
Table 8–12.Use of antibiotics in patients with renal failure and hepatic failure. ||Download (.pdf) Table 8–12. Use of antibiotics in patients with renal failure and hepatic failure.
| || ||Approximate Half-Life in Serum ||Proposed Dosage Regimen in Renal Failure || || || |
| ||Principal Mode of Excretion or Detoxification ||Normal ||Renal Failurea ||Initial Doseb ||Maintenance Dose ||Removal of Drugs by Dialysis ||Dose After Dialysis ||Dosage in Hepatic Failure |
|Acyclovir ||Renal ||2.5-3.5 h ||20 h ||2.5 mg/kg ||2.5 mg/kg q24h ||Yes ||2.5 mg/kg ||NC |
|Ampicillin ||Tubular secretion ||0.5-1 h ||8-12 h ||1 g ||1 g q8-12h ||Yes ||1 g ||NC |
|Azlo-, mezlo-, piperacillin ||Renal 50%-70%; biliary 20%-30% ||1 h ||3-6 h ||3 g ||2 g q6-8h ||Yes ||1 g ||1-2 g q8h |
|Azithromycin ||Mainly liver/biliary ||> 24 h ||> 24 h ||500 mg ||250 mg/d ||No ||No ||NC |
|Carbenicillin ||Tubular secretion ||1 h ||16 h ||4 g ||2 g q12h ||Yes ||2 g ||NC |
|Ciprofloxacin ||Renal and hepatic ||4 h ||8.5 h ||0.5 g ||0.25-0.75 g q24h ||No ||None ||NC |
|Clindamycin ||Hepatic ||2-4 h ||2.4 h ||0.6 g IV ||0.6 g q8h ||No ||None ||0.3-0.6 q8h |
|Erythromycin ||Mainly hepatic ||1.5 h ||1.5 h ||0.5-1 g ||0.5-1 g q6h ||No ||None ||0.25-0.5 g q6h |
|Fluconazole ||Renal ||30 h ||98 h ||0.2 g ||0.1 g q24h ||Yes ||Give q24h dose ||NC |
|Ganciclovir ||Renal ||3 h ||11-28 h ||1.25 mg/kg ||1.25 mg/kg q24h ||Yes ||Give q24h dose ||NC |
|Imipenem ||Glomerular filtration ||1 h ||3 h ||0.5 g ||0.25-0.5 g q12h ||Yes ||0.25-0.5 g ||NC |
|Levofloxacin || ||360-480 min ||360-480 min ||250-500 mg ||250-500 mg/d ||No ||No ||Avoid use |
|Meropenem || ||60 min ||180 min ||1000 mg ||1000 mg q8h ||Yes ||500 mg q4h ||NC |
|Metronidazole ||Hepatic ||6-10 h ||6-10 h ||0.5 g IV ||0.5 g qh ||Yes ||0.25 g ||0.25 g q12h |
|Moxifloxacin ||Renal ||720 min ||720 min ||400 mg ||400 mg ||No ||No ||Avoid use |
|Nafcillin ||Hepatic 80%, kidney 20% ||0.75 h ||1.5 h ||1.5 g ||1.5 g q5h ||No ||None ||2-3 g q12h |
|Penicillin G ||Tubular secretion ||0.5 h ||7-10 h ||1-2 million units ||1 million units q8h ||Yes ||500,000 units ||NC |
|Ticarcillin ||Tubular secretion ||1.1 h ||15-20 h ||3 g ||2 g q6-8h ||Yes ||1 g ||NC |
|Trimethoprim-sulfamethoxazole ||Some hepatic ||TMP 10-12 h; SMZ 8-10 h ||TMP 24-48 h; SMZ 18-24 h ||320 mg TMP + 1600 mg SMZ ||80 mg TMP + 400 mg SMZ q12h ||Yes ||80 mg TMP + 400 mg SMZ ||NC |
|Vancomycin ||Glomerular filtration ||6 h ||6-10 d ||1 g ||1 g q6-10d based on serum levels ||None ||None ||NC |
|Voriconazole ||Hepatic ||360 min ||360 min ||6 mg/kg IV × 2 doses ||100-200 mg oral q12h ||No ||None ||Normal load and ½ maintenance |
|Cefazolin ||Renal ||90 min || ||0.5 g ||0.5 g qd ||Yes ||0.5 g ||NC |
|Cefuroxime ||Renal ||80 min || ||1-2 g ||1-2 g qd ||Yes ||0.5 g ||NC |
|Cefotetan ||Renal ||150 min || ||0.5-1 g ||0.5-1 g qd ||Yes ||0.5 g ||NC |
|Cefoxitin ||Renal ||60 min || ||1-2 g ||1-2 g qd ||Yes ||0.5 g ||NC |
|Ceftriaxone ||Renal and hepatic ||480 min || ||1-2 g ||1-2 g qd ||No || ||NC |
|Ceftazidime ||Renal ||120 min || ||0.5-1 g ||0.5-1 g qd ||Yes ||0.5 g ||NC |
|Cefepime ||Renal ||120 min ||600 min ||1-2 g IV ||1-2 g IV q12h ||Yes ||1 g q48h ||NC |
In conclusion, surgery can result in infection (such as SSI), but may also be the adjunct treatment to obtain source control in many infectious processes (ie, surgical infections). In the former, prevention by implementing processes of care (eg, timely provision of perioperative antibiotics, maintenance of strict sterile techniques) and patient risk factors optimization prior to surgery should be the goal of every surgeon, as SSI remains one of the biggest health care-associated perioperative challenges. For the latter (surgical infections), source control is the cornerstone in the prevention of systemic progression of the infection into sepsis, septic shock, and/or MODS. Alongside surgical treatment of infections, antibiotic stewardship with appropriate timing, duration, and choice of antibiotics are needed now more than ever to prevent the emergence of resistant organisms as well as C difficile infection.
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