1352 Antifungal Therapy in the Surgical Patient

Appropriate management of HCV exposure depends on the status No preexposure or postexposure prophylaxis for HCV is currently
of the source patient, as follows. recommended.
If HCV Ab positive:
  

   1. Immune globulin not recommended by CDC

nn Check to see if HCV RNA has previously been ordered, to deter- nn Little evidence that humoral response critical in clearance
mine chronicity. nn No efficacy in chimpanzees to prevent infection
nn If no HCV RNA available, order HCV RNA PCR. 2. Interferon (IFN) ± ribavirin not recommended
nn Toxic
  

If HCV RNA is undetectable:

   nn IFN may only be effective in established infection
nn Source patient previously treated and cleared infection, attaining nn No effect in (underpowered) Japanese study
sustained virologic response, nn Early identification and treatment of infection offers best
or course of action currently for occupationally acquired HCV.
nn Source patient independently spontaneously cleared HCV
nn HCW not at risk for acquiring HCV Suggested Readings
  

If HCV RNA detectable: AASLD & IDSA joint guidelines on Management of Acute Hepatitis C Infec-
   tion: https://www.hcvguidelines.org/unique-­populations/acute-­infection.
nn Source patient is at risk for transmitting HCV to HCW CDC. Diagnoses of HIV Infection in the United States and dependent areas,
  
2016. HIV Surveillance Supplemental Report. 2018;23(1).
If source patient is of unknown HCV status: Edlin BR, Eckhardt BJ, Shu MA, Holmberg SD, Swan T. Toward a more ac-
  

nn Draw HCV Ab curate estimate of the prevalence of hepatitis C in the United States. Ann
Intern Med. 2012;156(4):271–278.
nn HCV Ab should be followed by HCV RNA PCR if positive
Kamal SM. Acute hepatitis C: a systematic review. Am J Gastroenterol.
nn If high-­risk patient, can draw HCV RNA PCR with initial draw 2008;103(5):1283–1297.
  

If source patient has chronic HCV (HCV Ab and HCV RNA posi- Kuhar D, Henderson D, Struble K, Heneine W, Thomas V, Cheever L, US
tive), exposed HCW should have: public health service working group, et al. updated US public health ser-
   vice guidelines for the management of occupational exposures to human
nn HCV Ab test and LFT at baseline (time of exposure) and at 6 immunodeficiency virus and recommendations for postexposure pro-
months post exposure phylaxis. Infect Control Hosp Epidemiol. 2013;34(9):875–892. https://doi.
nn HCV RNA at 4 to 6 weeks postexposure org/10.1086/672271.
   Makary MA, Al-­Attar A, Holzmueller CG, et al. Needlestick injuries among
Because of the high rates of spontaneous clearance of acute HCV surgeons in training. N Engl J Med. 2007;356(26):2693–2699.
by 6 months, there is some variance in recommendations on timing National Institute for. Occupational Safety and Health Alert: Preventing Needle-
of treatment. The American Association for the Study of Liver Dis- stick Injuries in Health Care Settings. Washington, DC: National Institute
eases and Infectious Disease Society of America joint guidelines on for Occupational Safety and Health; 1999. Publication no. 2000-­108.
Schillie S, Vellozzi C, Reingold A, et al. Prevention of hepatitis B virus in-
acute HCV recommend that the patient and their clinician jointly fection in the United States: recommendations of the advisory com-
decide whether a delay in treatment initiation while monitoring for mittee on immunization practices. MMWR Recomm Rep. 2018;67(No.
spontaneous clearance is favored, and even if the decision is instead RR-­1):1–31.
to initiate treatment during acute infection, monitoring HCV RNA Spradling PR, Rupp LB, Moorman AC, Lu M, Teshale EH, Gordon SC, et al.
first for a minimum of 12 to 16 weeks before starting treatment is rec- Hepatitis B and C virus infection among 1.2 million persons with access
ommended. In such cases, the same HCV regimens used for chronic to care: factors associated with testing and infection prevalence. Clin Infect
HCV are used for acute HCV, are safe and well tolerated, and are Dis. 2012;55(8):1047–1055.
>99% likely to result in cure. However, we advocate immediate treat- Updated US. Public health services guidelines for the management of occupa-
ment of acute HCV for HCWs who are found to have HCV RNA tional exposures to HBV, HCV, and HIV and recommendations for post-­
exposure prophylaxis. MMWR. 2001;50(RR 11):1–42.
positive at 4 weeks postexposure. (Risk-­benefit ratio favors this, espe- Weiss ES, Makary MA, Wang T, et  al. Prevalence of blood-­borne patho-
cially with regard to the availability of safe, well-­tolerated, and highly gens in an urban, university-­based general surgical practice. Ann Surg.
effective treatment regimens with acceptable cost, which minimize 2005;241:803–809.
the impact on the HCW, their potentially exposed family, and their
patients over the period of high HCV viral load.)

Antifungal Therapy in emerging pathogens such as Fusarium. Superficial fungal infections

are rarely dangerous, but invasive fungal infections continue to be

the Surgical Patient associated with serious complications and a high mortality. Surgi-
cal patients frequently have many of the risk factors associated with
invasive fungal infection, including critical illness, recent abdominal
Ashley D. Meagher, MD, MPH, and Heather L. Evans, MD, MS surgery, solid organ transplantation, exposure to broad-­spectrum
antibiotics, as well as any additional immunocompromised states.
Identification and diagnosis of infection can be difficult, which fre-

N osocomial fungal infections are an increasing problem in hos-

pitalized surgical patients. These infections are frequently seen
in critically ill surgical patients, with bloodstream infection the most
quently delays initiation of appropriate antifungal therapy. Surgeons
may be involved in the care of patients with invasive fungal infec-
tions in many settings, from debridement of infected tissue to treat-
common etiology. The most commonly seen infections are caused ment in a critical care unit. This chapter summarizes fungal infections
by Candida species. Other significant fungal pathogens in surgi- typically encountered, with special emphasis on the use of antifungal
cal patients include: Aspergillus, Cryptococcus, mucormycosis, and therapy as treatment (Table 1).
 P R E O P E R AT I V E A N D P O S TO P E R AT I V E C A R E 1353

TABLE 1  Patient Types and Treatment Options for Fungal Infections

Primary and Alternative Treat-
Infection Patient Type ments Duration of Therapy Comments
Candidemia Critically ill, abdominal Primary 14 days after clearance Remove vascular access
surgery, cancer Caspofungin 70 mg × 1, then 50 of blood cultures devices, if possible.
chemotherapy, mg/day IV Longer if ocular Do not use fluconazole for
vascular access, burns, Anidulafungin 200 mg × 1, then involvement. If critically ill patients.
parenteral nutrition 100 mg/day IV possible, can switch Evaluate for ocular involve-
Micafungin 100 mg/day IV to oral agent to ment with fundoscopic
Fluconazole 800 mg × 1, then complete therapy examination.
400 mg/day IV or PO once patient has
Alternative stabilized.
Deoxycholate AmB 0.7–1.0 mg/
kg/day IV
Lipid AmB 3–5 mg/kg/day IV
Voriconazole 6 mg/kg BID × 2
doses, then 4 mg/kg BID
Candiduria/UTI Urinary catheter, DM, Primary 14 days Patients with asymptomatic
kidney transplant Fluconazole 200–400 mg/day IV candiduria do not routinely
recipients or PO need to be treated. Excep-
tions are neutropenia or
planned instrumentation.
Alternative 1–7 days
Deoxycholate AmB 0.3–0.6 mg/
kg/day IV
Flucytosine 25 mg/kg QID PO 7–10 days
Oropharyngeal Immunocompromised, Primary 7–14 days Use topical therapy for mild
candidiasis radiotherapy, ill-­fitting Clotrimazole 10 mg 5 times/day disease; relapses more com-
dentures PO mon with echinocandins.
Nystatin suspension (100,000 U/
mL) 4–6 mL QID PO
Fluconazole 100–200 mg/day PO
Alternative
Itraconazole solution 200 mg/day
PO
Posaconazole 400 mg BID × 3
days, then 400 mg/day BID PO
Voriconazole 200 mg BID PO
Caspofungin 70 mg × 1, then 50
mg/day IV
Anidulafungin 200 mg × 1, then
100 mg/day IV
Micafungin 100 mg/day IV
Deoxycholate AmB oral suspen-
sion 100 mg/mL QID PO or 0.3
mg/kg IV daily
Esophageal can- Immunocompromised Primary 14–21 days Relapses may be more com-
didiasis Fluconazole 200–400 mg/day PO mon with echinocandins.
or 400 mg/day IV
Alternative
Micafungin 150 mg/day IV
Caspofungin 70 mg × 1, then 50
mg/day IV
Anidulafungin 200 mg/day IV
Deoxycholate AmB 0.3–0.7 mg/
kg/day IV
Itraconazole 200 mg/day PO
Voriconazole 200 mg BID IV or
PO
Posaconazole 400 mg BID PO
1354 Antifungal Therapy in the Surgical Patient

TABLE 1  Patient Types and Treatment Options for Fungal Infections—cont’d

Primary and Alternative Treat-
Infection Patient Type ments Duration of Therapy Comments
Vulvovaginal Antibacterial therapy, DM Topical therapy (e.g., clotrimazole, Schedules vary by Vulvovaginal candidiasis, even
candidiasis nystatin, miconazole) agent if recurrent, usually does not
Fluconazole 150 mg × 1 PO result from an immunocom-
promised state.
Aspergillosis Abnormalities of neutro- Primary Length of treatment Consider monitoring vori-
phil number or func- Voriconazole 6 mg/kg BID × 2, not clear conazole and posaconazole
tion, structural lung then 4 mg/kg/day ± echino- levels to help guide therapy.
abnormalities, burns candin
Alternative
Lipid AmB 3–5 mg/kg/day
Caspofungin 70 mg × 1, then 50
mg/day IV
Posaconazole 800 mg/day in 2–4
divided doses IV or PO
Mucormycosis Systemic immunosup- Primary Length of treatment Debridement and excision are
pression, burns, Lipid AmB 5–7.5 mg/kg/day ± not clear often needed.
trauma, near drown- posaconazole If patient is stable, consider
ing, uncontrolled DM, switching to posaconazole
deferoxamine use after 3 weeks AmB.

AmB, Amphotericin B; BID, twice daily; DM, diabetes mellitus; IV, intravenously; PO, orally; QID, four times daily; UTI, urinary tract infection.

nn SPECIFIC FUNGI Surgical patients at elevated risk for invasive candidiasis are fre-
quently critically ill with need for central venous catheter, broad-­
Candida spectrum antibiotics, hemodialysis, or total parenteral nutrition. In
Candida species are the most common fungal pathogens in surgical addition, surgical diseases, such as perforation of the gastrointestinal
patients, composing approximately 80% of fungal nosocomial infec- tract, intestinal anastomotic leak, or pancreatitis, increase the risk for
tions. These fungi are commensals of the human gastrointestinal (GI) invasive candidiasis. Most frequently, invasive infection is in the form
tract, genital tracts, and skin. Infections are almost always of endog- of candidemia; however, peritonitis, endocarditis, mediastinitis and
enous origin, particularly when host defenses break down or are meningitis may occur in certain postsurgical patient populations.
breached. Patients with a central venous catheter, prolonged expo- Approximately 50% of blood cultures fail to demonstrate candidemia,
sure to broad-­spectrum antibiotics, or those who have had a recent so critically ill patients with the risk factors of upper gastrointesti-
operation, particularly when there has been GI contamination, are nal perforation, prolonged broad-­spectrum antibiotic treatment, or
at greater risk for candidiasis. Iatrogenic spread between patients by known Candida colonization should be empirically treated with anti-
healthcare workers can affect fungal colonization patterns and subse- fungal therapy. 
quent infecting species, as can exposure to antifungal agents.
There are at least 15 species of Candida identified; however, more
than 90% of invasive infections are caused by C. albicans, C. parap- Other Fungi
silosis, C. glabrata, C. tropicalis, and C. krusei. There are increasing Other invasive fungal infections, once rare, are on the rise, likely sec-
infectious complications with other Candida species such as C. dubli- ondary to the increasing number of immunocompromised patients.
niensis, C. lusitaniae, and C. auris. C. albicans still comprises approxi- Patients with advanced malignancy, hematologic disease, HIV, as well
mately one-­half of infections, and the prevalence of non-­albicans as organ transplant recipients and those with autoimmune condi-
species vary based on geographic location and special populations. tions are at increased risk for invasive fungal infection. Aspergillus is
Candida is the third most common bloodstream pathogen, and the most common species encountered. Patients with abnormal lung
accounts for 9% to 10% of all bloodstream infections in hospitalized anatomy or function, such as such as cystic fibrosis, chronic lung dis-
patients. Awareness of non-­albicans species is crucial because they eases, lung transplantation, or prolonged mechanical ventilation may
frequently have reduced susceptibilities or intrinsic resistance to be chronically colonized with Aspergillus or other molds. These may
common antifungal therapies. progress to invasive or saprophytic disease. Invasive aspergillosis most
Infection resulting from Candida can be broadly divided into commonly manifests as a progressive, cavitary pulmonary infection
mucosal and systemic disease. Mucocutaneous infections are gener- that can result in hemoptysis. Cavitary lesions usually are seen on
ally benign and limited to local overgrowth. These are mediated by chest radiograph or computed tomography of the chest. Cutaneous
changes in local flora. Oropharyngeal and candidal esophagitis gen- infections may occur after a break in the skin barrier, either because of
erally occur in immunocompromised patients, including those with burn injury, or after an operation in a severely immunocompromised
human immunodeficiency virus (HIV), those receiving chemother- patient. Mucormycosis, Cryptococcus, and infection with endemic
apy, or being treated with corticosteroids. Cutaneous and vulvovagi- fungi (Histoplasma, Coccidioides, Blastomyces) are rarely seen in pri-
nal candidiasis are sometimes triggered by antimicrobial use, poor mary surgical patients outside of organ transplantation or following
glycemic control, or may be spontaneous. burn or traumatic injuries contaminated by soil. These infections may
 P R E O P E R AT I V E A N D P O S TO P E R AT I V E C A R E 1355

be reactivated with initiation of immunosuppressive medications or as first-­line therapy for established infections. The dose for invasive
in severe critical illness.  fungal infections varies depending on the formulation used, and it is
imperative that this be taken into account. As with voriconazole, IV
nn ANTIFUNGAL AGENTS dosing should be reduced in patients with renal impairment because
of toxicity from accumulation of the associated vehicle. Side effects of
Azoles posaconazole are common and include fever, nausea, diarrhea, head-
The azoles are a commonly used class of antifungal agents with activ- ache, hypokalemia, and thrombocytopenia. Long QT syndrome and
ity against a broad range of fungi. These drugs inhibit ergosterol hepatotoxicity are less common but serious complications. Posacon-
biosynthesis, thereby impairing formation of the fungal cell mem- azole also is associated with multiple drug interactions similar to
brane. Azoles are available in oral, intravenous (IV), or topical forms those with other azoles. 
depending on the specific agent. Azoles have the potential for multi-
ple drug interactions via the cytochrome P450 system, and care must
be taken when they are administered at the same time as other drugs Itraconazole
metabolized by these isoenzymes.  Itraconazole’s spectrum of activity is similar to that of fluconazole.
It is active against Candida but also against some filamentous and
dimorphic fungi, including Aspergillus, Blastomyces, and Histo-
Fluconazole plasma. It also can be used to treat onychomycosis. In some coun-
Fluconazole is the predominant azole used to treat fungal infections tries, itraconazole is available for IV therapy. Itraconazole has been of
in surgical patients. It is effective against most species of Candida and limited use in surgical patients because of the erratic bioavailability of
is used often as first-­line therapy. It is available in oral and IV formu- the oral capsule, which has improved with the oral cyclodextrin solu-
lations and is generally well tolerated. Fluconazole has excellent activ- tion. Additional factors limiting its use include the need for drug level
ity against C. albicans but has variable activity against C. glabrata, monitoring, GI upset (particularly with the cyclodextrin solution),
which can account for up to 25% of candidal infections. It is inactive hepatic toxicity, and negative inotropic cardiac effects that can cause
against C. krusei. Fluconazole is a first-­line agent for oropharyngeal or worsen congestive heart failure. 
and esophageal candidiasis as well as for urinary tract infections
resulting from Candida. It also has a role in cases of invasive can- nn ECHINOCANDINS
didiasis in moderately ill, nonneutropenic patients, although dosing
needs to be significantly higher (400–800 mg/day). Dose adjustment The echinocandins (caspofungin, micafungin, and anidulafungin)
is required with renal dysfunction. The use of fluconazole has been are an important class of antifungal agents, and they have emerged
associated with hepatic toxicity, GI upset, rashes, and drug interac- as a preferred treatment class for many fungal infections. They act
tions. Resistance to fluconazole is on the rise, so sensitivity testing by inhibiting fungal cell wall formation and have fungicidal activity
should be performed in high-­risk patients.  against almost all Candida species. Echinocandins are used widely
for the treatment of invasive candidiasis, especially in critically ill
and neutropenic patients. They also are used for empiric antifungal
Voriconazole therapy in immunocompromised patients with neutropenic fever.
Voriconazole is effective against most species of Candida and Asper- Echinocandins are first-­line therapy against invasive candidiasis
gillus and multiple other filamentous fungi. It is available in oral because they are fungicidal against a variety of Candida species,
and IV formulations. Voriconazole is the first-­line treatment for including fluconazole-­resistant C. glabrata and C. krusei. Treat-
invasive aspergillosis and can be used in cases of invasive candidia- ment failures have been reported with C. parapsilosis, which has
sis. It has excellent bioavailability, allowing for oral administration. some innate resistance to the echinocandins. Under selective pres-
Steady-­state levels are reached more rapidly with IV loading doses of sure, other species of Candida may develop resistance. They are not
6 mg/kg every 12 hours for 2 doses, followed by 4 mg/kg IV every ideal for cases of oropharyngeal and esophageal candidiasis. The
12 hours or 200 mg orally every 12 hours. Patients with renal dys- echinocandins inhibit growth of Aspergillus, but they are not fungi-
function should receive the oral form of voriconazole for mainte- cidal against that species. There may be a role for their use as salvage
nance because the cyclodextrin carrier used in the IV formulation therapy in refractory Aspergillus infections, but should be used in
can accumulate and may damage the kidneys. Patients with hepatic combination treatment. Experience suggests that this class is among
impairment should receive the standard loading dose, but the main- the safest and best tolerated of the antifungals available. They are
tenance dose should be decreased by 50%. Voriconazole is associ- available via the IV route only.
ated with multiple adverse reactions, most commonly visual changes
such as photophobia, reduction in visual acuity, and blurred vision.
Routine monitoring of drug levels is not recommended; however, Polyenes
monitoring can be helpful when there are concerns about efficacy Polyene antibiotics are a class of antimicrobial compounds that bind
or toxicity. Like fluconazole, voriconazole is associated with multiple to ergosterol, the main sterol in the fungal cell membrane, and cause
drug interactions.  depolarization. This increases membrane permeability and leads to
leakage of intracellular cations causing cell death. Amphotericin B
and nystatin are examples of polyene antimycotics. Amphotericin B
Posaconazole deoxycholate, which was the standard drug for the treatment of can-
Posaconazole is effective against a broad range of fungi, including didiasis for decades, demonstrates rapidly fungicidal in  vitro activ-
most species of Candida and Aspergillus and many filamentous fungi, ity against most species of Candida but is associated with significant
including the zygomycetes. It is available in oral suspension, delayed-­ nephrotoxicity. Because of this adverse effect, it is rarely used. Instead,
release tablets, and IV formulations. Oral suspension or delayed most physicians use a lipid-­based amphotericin B formulation, either
release tablets are indicated for prophylaxis of invasive Aspergillus and liposomal amphotericin B or amphotericin B lipid complex, when
Candida infections in patients at high risk of developing these infec- selecting a polyene agent. These lipid-­based compounds have much
tions because of being severely immunocompromised (e.g., recipients less toxicity than amphotericin deoxycholate, but are significantly
of hematopoietic stem cell transplant with graft-­versus-­host disease, more expensive. Because of this, amphotericin B is now primarily
those with hematologic malignancies with prolonged neutropenia used in salvage therapy of the most refractory invasive fungal infec-
from chemotherapy). Attainment of steady-­state levels can take a tions. Nystatin is frequently used to treat mucocutaneous candidiasis
week or longer, and for this reason it generally is not recommended in a powder, cream, or oral liquid form. 
1356 Antifungal Therapy in the Surgical Patient

nn COMMON FUNGAL INFECTIONS white patches on multiple surfaces of the oral mucosa, and erythema-
tous candidiasis (acute atrophic candidiasis), which occurs by itself or
Mucocutaneous Disease in association with the white patches. Symptoms include local pain,
Mucocutaneous fungal infections are very common, and their risk burning, and changes in taste perception. Microscopic examination
factors, including diabetes mellitus, obesity, treatment with antibiot- of scrapings of the involved area may help with the diagnosis if in
ics or steroids, and inflammatory skin diseases, are found frequently doubt.
in surgical patients. These infections can cause significant discomfort Oropharyngeal candidiasis is almost always caused by C albicans
but are rarely dangerous. Typical sites of infection include the skin, and usually responds to topical treatments such as clotrimazole tro-
oropharynx (thrush), genitalia, and esophagus. Patients with symp- ches, 10 mg 5 times daily, or nystatin suspension (nystatin “swish
tomatic superficial infection should be treated, but because Candida and swallow”). Systemic antifungal medication such as fluconazole
species normally exist on the skin and mucosal surfaces as commen- 100 to 200 mg daily, or itraconazole 200 mg daily, may be necessary
sals, culturing the organism from a superficial surface in the absence for oropharyngeal infections that do not respond to topical therapy.
of symptoms is not an indication for treatment. Treatment is typically for 7 to 14 days but may need to be extended,
depending on response to therapy. 
Cutaneous Candidiasis
Cutaneous candidiasis is almost always caused by C. albicans and may Esophageal Candidiasis
occur anywhere on the body but typically involve intertriginous areas Esophageal candidiasis usually occurs in patients with a highly com-
(candidal intertrigo). Warm, moist, and macerated skin sites, such as promised immune system. Additional risk factors include advanced
inframammary crease, large abdominal folds, the axillae, or the groin, liver disease and inhaled steroids. Usual symptoms include odyno-
are common sites of involvement and must be examined and treated. phagia, dysphagia, and retrosternal pain. Concurrent oropharyngeal
Open incisions, wounds, or decubitus ulcers being treated with moist candidiasis is common but not always present. Infection is generally
dressings are also at risk for infection. The affected area may be itchy, limited to the mucosa. Complications include dehydration and mal-
red, and moist. The skin can be eroded with whitish scaling at the nutrition resulting from poor oral intake, esophageal strictures, and
borders. Satellite lesions just beyond the border of the grossly affected even esophageal perforation.
area are common. Treatment is with oral fluconazole 200 to 400 mg daily. If the
Diagnosis generally is based on clinical appearance. Superficial patient is unable to tolerate oral therapy, fluconazole 400 mg daily
candidiasis can be treated with topical therapy. For moist macerated should be delivered intravenously. Therapy is typically for 14 to 21
skin, an antifungal powder formulation is preferable because of its days, depending on patient response. Oropharyngeal and esopha-
drying properties. Nystatin (100,000 units/g) and miconazole (2%) geal candidiasis refractory to fluconazole occasionally may develop
are available as either a powder or a cream. A variety of other antifun- in patients who are highly immunosuppressed or those previously
gal creams are also available, such as ketoconazole (2%) and clotrima- treated with an azole and have developed resistance. Alternative oral
zole (1%). More extensive infections may require oral azole drugs in options include itraconazole solution 200 mg/day, voriconazole 200
conjunction with topical treatments.  mg twice daily, and posaconazole 400 mg twice daily. These regimens
cost more and are potentially more toxic than fluconazole. Treat-
Candidal Vulvovaginitis ment may be ineffective if resistance has developed to the entire azole
Candidal vulvovaginitis is common, and most women will have at class. IV antifungal therapy with echinocandins (micafungin 150 mg
least one episode during their lifetime. Most infections are caused daily; caspofungin 70 mg loading dose, then 50 mg daily; and anid-
by C. albicans and represent a patient’s own organisms. Risk factors ulafungin 200 mg daily) can be effective, but use is associated with
include antibiotics, diabetes mellitus, and pregnancy. Vulvovaginitis higher relapses; therefore, recommended dosages are higher. Sys-
may be seen with local irritation, itching, erythema, thick white vagi- temic amphotericin B deoxycholate or lipid formulations are another
nal discharge, dysuria, and dyspareunia. Patients often make a self-­ option, but can be associated with substantial toxicity. Patients at
diagnosis of “yeast” vaginitis. This can be confirmed by identifying significant risk for oropharyngeal and esophageal candidiasis, such
Candida elements (pseudohyphae and blastoconidia) on microscopic as those receiving cytotoxic chemotherapy or high intensity immu-
evaluation of a 10% potassium hydroxide-­treated sample. Fungal cul- nosuppression or those who have advanced HIV, should be treated
tures are usually neither necessary nor helpful. with prophylaxis. Topical agents such as nystatin or clotrimazole
There are multiple intravaginal treatment options, including oral are generally effective. Systemic fluconazole 400 mg by mouth or IV
nystatin tablets (100,000 units/tablet), various topical azole creams daily also may be effective as suppressive therapy in cases of recurrent
and vaginal suppositories (e.g., miconazole 2%, butoconazole 2%, infection. 
clotrimazole 1%, terconazole 0.4% and 0.8%, tioconazole 6.5%,
miconazole cream 2% and 4% or suppositories at 100 and 200 mg)
and oral fluconazole (150 mg as a single dose). The duration of treat- Candiduria
ment varies with different agents and concentrations. Most infections Candiduria is a common finding in hospitalized surgical patients, or
can be treated with a single dose of oral medication or a 1-­to 3-­day those with long-­term indwelling urinary catheters. This may repre-
course of topical therapy. Some patients with recurrent or severe dis- sent a spectrum of clinical scenarios, from colonization and cysti-
ease require longer treatment with either 7 to 14 days of topical azole tis to more serious conditions such as upper urinary tract infection
or 150 mg of fluconazole in two sequential oral doses (second dose 72 or disseminated disease. It is often difficult to distinguish true uri-
hours after initial dose).  nary infection from mere colonization, particularly in patients with
indwelling urinary catheters. The decision to treat should be based on
Oropharyngeal Candidiasis the clinical scenario and not solely on the presence of yeast in urine
Oropharyngeal candidiasis mainly presents in immunosuppressed cultures.
patients, particularly after organ transplantation and in those with Treatment is indicated in patients who are symptomatic, neu-
advanced HIV. Additional risk factors include extremes in age, poorly tropenic, have renal allograft, or those with urologic manipulation.
controlled diabetes mellitus, nutritional deficiencies, inadequately fit- Removal or exchange of urinary catheters may be helpful in clear-
ting dentures, systemic or inhaled steroids, radiotherapy, and cyto- ing candiduria. Oral fluconazole (200 mg or 3 mg/kg daily) for 7 to
toxic chemotherapy. Presentation of oropharyngeal candidiasis in 14 days is recommended for the treatment of cystitis resulting from
a patient without risk factors should spark a search for underlying Candida. Alternatives include systemic amphotericin B deoxycholate
disease. This may be the first manifestation of advanced HIV. Clinical or oral flucytosine, although the latter frequently results in the rapid
manifestations include thrush, which is characterized by curd-­like, development of resistance. Bladder irrigation with amphotericin B
 P R E O P E R AT I V E A N D P O S TO P E R AT I V E C A R E 1357

deoxycholate may be useful in cases of refractory cystitis from azole-­ gastrointestinal tract perforation, anastomotic breakdown, and mul-
resistant strains. Lipid formulations of amphotericin B should be tifocal colonization. Patients should be classified as low or high risk,
avoided because they do not achieve adequate concentrations in the based on the presence of these risk factors.
urinary system. Patients with persistent candiduria and additional Diagnosis of an intraabdominal fungal infection should be based
risk factors should be evaluated for presence of a fungus ball or renal on culture results from intraoperative samples or by percutaneous
parenchymal disease.  aspiration. Intraoperative fungal cultures or percutaneous aspiration
should be obtained for patients at high risk of intraabdominal fungal
nn FUNGAL BLOODSTREAM INFECTIONS infection to identify the presence of resistant organism and to guide
antimicrobial therapy. The presence of yeast in samples obtained
Fungi are the fourth most common pathogen isolated in bloodstream from an existing surgical drain may simply represent colonization
infections overall and the third most common pathogen in intensive and not necessarily an intraabdominal infection. The Surgical Infec-
care units in the United States. The majority of cases are attributed to tion Society recommends against empiric antifungal treatment in
Candida species, in particular C. albicans. Candidemia occurs more low-­risk patients, as well as most high-­risk patients. However, patient
commonly at the two extremes of age. Despite advances in pharma- with upper gastrointestinal perforation who are critically ill seem to
cologic agents, fungal bloodstream infections continue to carry an be at even higher risk, so empiric antifungal therapy should be con-
associated mortality rate of between 40% and 60%. sidered in this specific population.
As with other candidal infections, risk factors include prolonged Early source control is essential in managing these infections.
antibiotics treatment, total parenteral nutrition, neutropenia, immu- Antifungal treatment with fluconazole is appropriate for most
nosuppression, hemodialysis, previous fungal colonization, presence patients with infection due to C. albicans. An echinocandin should
of an intravascular catheter, major surgery, and burns. Prolonged be used for critically ill patients and those with isolates likely to be
critical illness increases the risk of colonization with Candida, which resistant to the azoles. The optimal duration of treatment is unclear.
then increases the risk of bloodstream infection. It is believed that A recent multinational expert panel recommended treatment for
once colonization occurs, Candida obtains access to the bloodstream 10 to 14 days for intraabdominal Candida infections. However, the
via translocation across the mucosal barrier in the GI tract, IV cathe- Surgical Infection Society’s Study to Optimize Peritoneal Infection
ter, or from an invasive localized infection. Blood cultures remain the Therapy evaluated the duration of treatment for patients with com-
gold standard for diagnosis; however, sensitivity of blood cultures is plicated intraabdominal infections and demonstrated that 4 days
less than 50%. Newer diagnostic assays, including polymerase chain of treatment following adequate source control resulted in similar
reaction, beta-­D-­glucan, and T2Candida, are still undergoing inves- outcomes compared with patients who received a longer course of
tigation and are not widely used. C. glabrata has been increasing and therapy. Although patients with fungal infections were included
now composes about one-­fourth of bloodstream isolates. This organ- in that study, it is unclear whether these recommendations apply
ism has an increased likelihood of resistance to azoles and potential to this group. The current Infectious Diseases Society of America
for multidrug resistance. Sensitivity testing should be performed on guideline for management of candidiasis recommends that duration
all candidal bloodstream isolates. of treatment be determined by the adequacy of source control and
Treatment recommendations vary for specific patient popula- clinical response. 
tions, taking into consideration recent drug exposure and risk factors
for infection due to resistant strains. Fluconazole remains a reason- nn FUNGAL SURGICAL SITE INFECTIONS
able option for noncritically ill patients who have no previous expo-
sure to azoles and lack additional risk factors for C. glabrata (e.g., Approximately 3% of surgical site infections (SSIs) are fungal, with
advanced age, malignancy, diabetes mellitus). Fluconazole should be C. albicans being the most common fungal pathogen. Although infre-
given with an initial loading dose of 800 mg (12 mg/kg), followed by quent, these infections are important to recognize because there have
400 mg (6 mg/kg) daily. Echinocandins are preferred for treatment been case reports of C. albicans causing necrotizing infections at a
of patients with greater risk factors, including neutropenic patients, surgical or central line site. Certain patient populations, such as those
and those at risk for infection with C. glabrata or C. krusei isolates. suffering from traumatic injuries, burns, or secondary or tertiary
Echinocandin dosing recommendations include: caspofungin at a peritonitis are at higher risk of developing fungal SSIs.
loading dose of 70 mg, then 50 mg daily; micafungin 100 mg daily; or Burn patients are at particularly high risk, with fungus responsible
anidulafungin at a loading dose of 200 mg, then 100 mg daily. First-­ for approximately 20% to 25% of burn wound infections, often as one
line therapy in neutropenic patients remains echinocandins, however isolate of a polymicrobial infection. Fungal wound infections in this
liposomal amphotericin B formulations (3–5 mg/kg daily) also may population typically occur approximately 2 weeks after burn injury
be used. Patients should have blood cultures drawn every 1 to 2 days and have been associated with a greater mortality. It is unclear if fun-
to monitor for clearance. Treatment should continue for 2 weeks after gal SSIs are the direct cause of death or simply represent a more severe
the first documented negative blood culture. disease state in these patients. Diagnosis of a fungal wound infection
Central venous catheters should be removed as early as possible in in burn wounds requires histopathologic evidence of fungal invasion
patients with candidemia because it may be primary source of infec- into viable tissue. The presence of fungi in necrotic tissue is consid-
tion or become infected secondarily. Retention of the catheter may ered to represent colonization. These patients require both surgical
be considered in patients with implanted access devices and candi- debridement as well as systemic antifungal therapy.
demia in the setting of cytotoxic chemotherapy and neutropenia. All Both Candida and Aspergillus have infrequently been implicated
patients with candidemia should have a dilated funduscopic exami- in poststernotomy wound infections, including osteomyelitis and
nation by an ophthalmologist within the first week after diagnosis to mediastinitis. The mainstay of treatment is surgical debridement and
evaluate for chorioretinitis or endophthalmitis. several months of antifungal therapy. 

Intraabdominal Fungal Infections nn FUNGAL PULMONARY INFECTIONS

Intraabdominal fungal infections occur as a result perforation of the Fungi represent only a small fraction of pathogens responsible for
upper gastrointestinal tract, as a complication of an intra­abdominal pulmonary infections, but they are important to recognize in light
operation or, less commonly, from disseminated disease. Candida is of the growing population of immunosuppressed patients. Opportu-
the most commonly isolated species, and mortality rates range from nistic organisms most commonly cause fungal pneumonias, whereas
20% to 64%. Risk factors for Candida intraabdominal infections pulmonary infections due to endemic fungi are rare in surgical
include pancreatic necrosis, recurrent abdominal operation, upper patients.
1358 Use of Opioids in the Postoperative Period

Candida Although this infection typically affects immunocompromised

Candidal pneumonia is very rare, despite Candida being a common patients, it may also be seen after traumatic injuries, near-­drownings,
organism found in respiratory secretions. Most cases are related to or burns. Additional risk factors include poorly controlled diabetes
disseminated Candida infection arising from distant sites and usually mellitus, malignancy, and treatment with the iron chelator defer-
occur among patients with additional risk factors. As with most Can- oxamine. Because of its invasive nature, this infection carries sig-
dida infections, prolonged antibiotic use, hematologic malignancies, nificant morbidity, with mortality rates greater than 50%. The most
and other immunocompromised states are the primary risk factors. common sites of mucormycosis include the sinuses, respiratory
Definitive diagnosis of Candida pneumonia is based on isolating the tract, and skin. Less commonly, the GI tract may be involved. Infec-
organism from lung tissue samples because growth of Candida from tion is commonly locally invasive to adjacent structures such as the
respiratory secretions generally indicates asymptomatic colonization orbits, brain, and blood vessels, leading to extensive tissue destruc-
and should not be treated. There are no clear guidelines for treatment tion. Vascular invasion may result in serious complications such as
of primary Candida pneumonia. Most cases have been treated with massive hemorrhage. Pulmonary mucormycosis is characterized by
amphotericin B deoxycholate or lipid formulations, although milder angioinvasion and a high degree of tissue necrosis leading to rapidly
cases have been treated successfully with fluconazole. Disseminated progressive pneumonia, development of cavitations, and hemopty-
disease should be treated similarly to candidemia.  sis. Reversed “halo” sign may be an early radiographic finding but
is nonspecific and also may be seen in aspergillosis. Symptoms of
pulmonary infection are nonspecific, with patients typically having
Aspergillus fever and hemoptysis.
Invasive aspergillosis is an increasingly important problem in surgical Definitive diagnosis of mucormycosis requires histologic evidence
patients, particularly the immunocompromised patients. It remains of tissue invasion, but bronchoalveolar lavage is helpful in making a
an uncommon disease but carries significant mortality. Early epide- diagnosis. Management of this disease requires a multidisciplinary
miologic studies in the United States have estimated its incidence to approach. This includes correction of metabolic abnormalities, reduc-
be 12 cases per 1 million people per year. tion of immunosuppression medications, and excision or debride-
Invasive aspergillosis is most commonly seen as a progressive, ment of infected tissues. Aggressive surgical debridement is key to
cavitary pulmonary infection that can result in hemoptysis. Com- preventing further invasion. This is particularly important if there is
mon symptoms include fever, dyspnea, cough, and pleuritic chest angioinvasion or necrosis. Liposomal amphotericin B at doses of at
pain. However, one-­third of patients are asymptomatic initially. Cavi- least 5 mg/kg per day is recommended. Posaconazole may be used
tary lesions are usually identified on plain radiographs or computed in combination with liposomal amphotericin B in refractory cases or
tomography of the chest. Other radiologic findings such as the “halo” for chemoprophylaxis and suppression. Echinocandins have not been
sign and “air crescent” sign are highly suggestive of Aspergillus pneu- shown to have in vitro activity against this species and are therefore
monia but nonspecific. Diagnosis can be difficult because of the rela- not recommended.
tive insensitivity of microscopy and culture to detect Aspergillus. A
definitive diagnosis requires both histopathologic evidence of infec- Suggested Readings
tion and culture of the organism from a sterile site. Galactomannan Bassetti M, Marchetti M, Chakrabarti A, et al. A research agenda on the man-
antigen detection, beta-­D-­glucan detection, and polymerase chain agement of intra-­abdominal candidiasis: results from a consensus of mul-
reaction are additional laboratory studies that may improve detection tinational experts. Intensive Care Med. 2013;39:2092–2106.
in certain high-­risk populations. Voriconazole remains the treatment Lipsett PA. Surgical critical care: fungal infections in surgical patients. Crit
of choice, amphotericin B is second-­line if voriconazole is not avail- Care Med. 2006;34(9 suppl):S215–S224.
able. Echinocandins (alone or in combination) should be reserved Mazuski JE, Tessier JM, May AK, et al. The Surgical Infection Society revised
as salvage therapy. Surgical resection of a pulmonary lesion may be guidelines on the management of intra-­abdominal infection. Surg Infect
indicated in patients with hemoptysis, bacterial superinfection, or as (Larchmt). 2017;18(1):1–76.
Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the
salvage in refractory infection; however, many patients with this level
management of candidiasis: 2016 update by the Infectious Diseases Soci-
of disease are too ill to safely undergo surgery.  ety of America. Clin Infect Dis. 2016;62(4):e1–50.
Patterson TF, Thompson 3rd GR, Denning DW, et al. Practice guidelines for
the diagnosis and management of aspergillosis: 2016 update by the Infec-
Mucormycosis tious Diseases Society of America. Clin Infect Dis. 2016;63(4):e1–e60.
Mucormycosis, also referred to as zygomycosis, is another very rare Sawyer RG, Claridge JA, Nathens AB, et al. Trial of short-­course antimicrobial
infection caused by one of the organisms belonging to the order therapy for intraabdominal infection. N Engl J Med. 2015;372:1996–2005.
Mucorales, most commonly Rhizopus spp. or Mucor spp. It has an
incidence of less than 2 per 1 million people per year.

Use of Opioids in the crashes. Unfortunately, young people are most afflicted by this
problem—20% of all deaths in persons between the ages of 24
Postoperative Period and 35 were due to opioids. The death rate from prescription opi-
oid overdose has quadrupled between 2000 and 2015. In addi-
tion, deaths from heroin and fentanyl are skyrocketing; the vast
Richard J. Barth Jr, MD majority of people who use these drugs start with prescription
opioids.
The rise in opioid overdose deaths has been temporally linked to
nn CURRENT OPIOID EPIDEMIC rising rates of opioid prescriptions, which have similarly quadrupled
between 2000 and 2015. In 2012 in the United States, 82 opioid pre-
Opioid overdose is now the leading cause of injury-related death scriptions were written per 100 persons. Over 5 million Americans
in the United States. There were 42,000 deaths from opioid over- report current opioid abuse (within 30 days), and 10 million report
dose in 2016 compared to 37,000 deaths from motor vehicle abuse during their lifetime.
1358 Use of Opioids in the Postoperative Period

Candida Although this infection typically affects immunocompromised

Candidal pneumonia is very rare, despite Candida being a common patients, it may also be seen after traumatic injuries, near-­drownings,
organism found in respiratory secretions. Most cases are related to or burns. Additional risk factors include poorly controlled diabetes
disseminated Candida infection arising from distant sites and usually mellitus, malignancy, and treatment with the iron chelator defer-
occur among patients with additional risk factors. As with most Can- oxamine. Because of its invasive nature, this infection carries sig-
dida infections, prolonged antibiotic use, hematologic malignancies, nificant morbidity, with mortality rates greater than 50%. The most
and other immunocompromised states are the primary risk factors. common sites of mucormycosis include the sinuses, respiratory
Definitive diagnosis of Candida pneumonia is based on isolating the tract, and skin. Less commonly, the GI tract may be involved. Infec-
organism from lung tissue samples because growth of Candida from tion is commonly locally invasive to adjacent structures such as the
respiratory secretions generally indicates asymptomatic colonization orbits, brain, and blood vessels, leading to extensive tissue destruc-
and should not be treated. There are no clear guidelines for treatment tion. Vascular invasion may result in serious complications such as
of primary Candida pneumonia. Most cases have been treated with massive hemorrhage. Pulmonary mucormycosis is characterized by
amphotericin B deoxycholate or lipid formulations, although milder angioinvasion and a high degree of tissue necrosis leading to rapidly
cases have been treated successfully with fluconazole. Disseminated progressive pneumonia, development of cavitations, and hemopty-
disease should be treated similarly to candidemia.  sis. Reversed “halo” sign may be an early radiographic finding but
is nonspecific and also may be seen in aspergillosis. Symptoms of
pulmonary infection are nonspecific, with patients typically having
Aspergillus fever and hemoptysis.
Invasive aspergillosis is an increasingly important problem in surgical Definitive diagnosis of mucormycosis requires histologic evidence
patients, particularly the immunocompromised patients. It remains of tissue invasion, but bronchoalveolar lavage is helpful in making a
an uncommon disease but carries significant mortality. Early epide- diagnosis. Management of this disease requires a multidisciplinary
miologic studies in the United States have estimated its incidence to approach. This includes correction of metabolic abnormalities, reduc-
be 12 cases per 1 million people per year. tion of immunosuppression medications, and excision or debride-
Invasive aspergillosis is most commonly seen as a progressive, ment of infected tissues. Aggressive surgical debridement is key to
cavitary pulmonary infection that can result in hemoptysis. Com- preventing further invasion. This is particularly important if there is
mon symptoms include fever, dyspnea, cough, and pleuritic chest angioinvasion or necrosis. Liposomal amphotericin B at doses of at
pain. However, one-­third of patients are asymptomatic initially. Cavi- least 5 mg/kg per day is recommended. Posaconazole may be used
tary lesions are usually identified on plain radiographs or computed in combination with liposomal amphotericin B in refractory cases or
tomography of the chest. Other radiologic findings such as the “halo” for chemoprophylaxis and suppression. Echinocandins have not been
sign and “air crescent” sign are highly suggestive of Aspergillus pneu- shown to have in vitro activity against this species and are therefore
monia but nonspecific. Diagnosis can be difficult because of the rela- not recommended.
tive insensitivity of microscopy and culture to detect Aspergillus. A
definitive diagnosis requires both histopathologic evidence of infec- Suggested Readings
tion and culture of the organism from a sterile site. Galactomannan Bassetti M, Marchetti M, Chakrabarti A, et al. A research agenda on the man-
antigen detection, beta-­D-­glucan detection, and polymerase chain agement of intra-­abdominal candidiasis: results from a consensus of mul-
reaction are additional laboratory studies that may improve detection tinational experts. Intensive Care Med. 2013;39:2092–2106.
in certain high-­risk populations. Voriconazole remains the treatment Lipsett PA. Surgical critical care: fungal infections in surgical patients. Crit
of choice, amphotericin B is second-­line if voriconazole is not avail- Care Med. 2006;34(9 suppl):S215–S224.
able. Echinocandins (alone or in combination) should be reserved Mazuski JE, Tessier JM, May AK, et al. The Surgical Infection Society revised
as salvage therapy. Surgical resection of a pulmonary lesion may be guidelines on the management of intra-­abdominal infection. Surg Infect
indicated in patients with hemoptysis, bacterial superinfection, or as (Larchmt). 2017;18(1):1–76.
Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the
salvage in refractory infection; however, many patients with this level
management of candidiasis: 2016 update by the Infectious Diseases Soci-
of disease are too ill to safely undergo surgery.  ety of America. Clin Infect Dis. 2016;62(4):e1–50.
Patterson TF, Thompson 3rd GR, Denning DW, et al. Practice guidelines for
the diagnosis and management of aspergillosis: 2016 update by the Infec-
Mucormycosis tious Diseases Society of America. Clin Infect Dis. 2016;63(4):e1–e60.
Mucormycosis, also referred to as zygomycosis, is another very rare Sawyer RG, Claridge JA, Nathens AB, et al. Trial of short-­course antimicrobial
infection caused by one of the organisms belonging to the order therapy for intraabdominal infection. N Engl J Med. 2015;372:1996–2005.
Mucorales, most commonly Rhizopus spp. or Mucor spp. It has an
incidence of less than 2 per 1 million people per year.

Use of Opioids in the crashes. Unfortunately, young people are most afflicted by this
problem—20% of all deaths in persons between the ages of 24
Postoperative Period and 35 were due to opioids. The death rate from prescription opi-
oid overdose has quadrupled between 2000 and 2015. In addi-
tion, deaths from heroin and fentanyl are skyrocketing; the vast
Richard J. Barth Jr, MD majority of people who use these drugs start with prescription
opioids.
The rise in opioid overdose deaths has been temporally linked to
nn CURRENT OPIOID EPIDEMIC rising rates of opioid prescriptions, which have similarly quadrupled
between 2000 and 2015. In 2012 in the United States, 82 opioid pre-
Opioid overdose is now the leading cause of injury-related death scriptions were written per 100 persons. Over 5 million Americans
in the United States. There were 42,000 deaths from opioid over- report current opioid abuse (within 30 days), and 10 million report
dose in 2016 compared to 37,000 deaths from motor vehicle abuse during their lifetime.