Antibiotics Part 2: Sites of Infection

Published September 2021

Yilin Zhang, MD¹; Brandon Fainstad, MD²; Mike Hori, MD³

1Assistant Professor, Department of General Internal Medicine, University of Washington, Valley Medical Center
2Assistant Professor, Department of General Internal Medicine, University of Colorado
3Department of Infectious Disease, Valley Medical Center

Objective(s)

Identify bacterial pathogens commonly responsible for community acquired and hospital acquired pneumonias, urinary tract infections, intra-abdominal infections, and meningitis.
- Differentiate between pathogens responsible for community acquired, hospital acquired, and aspiration pneumonia.
- Diagnose catheter associated UTI.
- Differentiate between pathogens typically responsible for non-purulent and purulent skin and soft tissue infections and necrotizing soft tissue infections.
- Differentiate between pathogens responsible for community acquired and hospital acquired intraabdominal infections.
Choose first and second line antibiotic regimens for the above infections based on bacterial pathogens.

Teaching Instructions

Plan to spend about 60 minutes preparing for this talk. Learners should receive a copy of the “Antibiotic man” handout to fill out as as you progress through the talk. You may also choose to print out the antibiogram in Antibiotics Part 1: Spectrum for your learners for reference. Use the interactive boards as an outline to present the talk while adding information from the teaching guide below.

This content can be delivered in multiple different ways:

As a broad and quick overview of the most common inpatient antibiotics. Anticipated time to deliver the talk with and without cases or other features: without cases is 45 minutes. The cases may take an additional 15 min.
As an a more in depth discussion on the evaluation and management of specific infections. The teaching scripts provided are for the more in depth discussions. Estimated times and corresponding cases are provided:
- Pneumonia – 20 min. Cases 1, 4b.
- UTI – 20 min, Case 4a.
- Skin and Soft Tissue Infections – 20 min. Cases 2, 5.
- Intraabdominal Infections – 15 min. Case 3.

The talk can be presented in two ways:

Project the “Interactive Board” OR
Reproduce your own drawing of the presentation on a whiteboard

Overview: The goal of this talk is to provide a broad framework for common community acquired and hospital acquired infections. Each site of infection is further broken down into common classification systems. Ask your learners about “Bugs” associated with each type of pneumonia before clicking on that category to reveal the answer. Based on the “Bugs”, have your learners propose a reasonable empiric antibiotic regimen (either IV or PO regimen, where appropriate). Emphasize that antibiotic regimens should always be narrowed/ geared towards the etiologic microorganism identified from culture data. Have learners use the antibiogram from Antibiotics Part 1: Spectrum to help guide their answers.

Pneumonia: Pneumonias can be categorized as community acquired pneumonia (CAP), hospital acquired pneumonia (HAP), or ventilator associated pneumonia (VAP). Aspiration is a common event and no formal criteria differentiate aspiration pneumonia from other types of pneumonia.

CAP¹ – Most common bacterial pathogens associated with CAP include Strep pneumoniae, GNRs, and atypical bacteria (Mycoplasma, Chlamydophylla, Legionella). However, because the new IDSA/ ATS guidelines no longer recognize healthcare associated pneumonia (HCAP) as a separate entity, there is a subset of patients with CAP that are at higher risk of colonization and infection with resistant organisms like MRSA and Pseudomonas. These at risk patients include 1) those with prior MRSA and Pseudomonas infection/colonization and 2) those hospitalized within the past 90 days with receipt of IV antibiotics.
- In the inpatient setting, CAP (without risk factors for MRSA and Pseudomonas) is best empirically covered by a beta-lactam (most commonly a 3rd generation cephalosporin like ceftriaxone) AND a macrolide (e.g., azithromycin). This is recommended regardless of the severity of pneumonia. Monotherapy with a respiratory fluoroquinolone (levofloxacin or moxifloxacin) is also an option.
  - Bonus: For stable outpatient adults with no risk factors for more resistant organisms (prior MRSA or Pseudomonas infection or recent IV antibiotics within the last 90 d) or significant comorbidities (heart, lung, liver, renal comorbidities, alcoholism, diabetes), amoxicillin 1 g TID, doxycycline 100 mg BID can be considered. Azithromycin can be considered only in areas with low pneumococcal resistance. Those with comorbidities should receive amoxicillin/clavulanate or cefpodoxime AND azithromycin or doxycycline. Alternatively, they can receive a respiratory fluoroquinolone as monotherapy.
- Patients with risk factors for MRSA and/or Pseudomonas should be treated with IV vancomycin (or linezolid) and IV piperacillin-tazobactam/ cefepime/ ceftazidime/ aztreonam/ meropenem. Patients being covered empirically for these more resistant organisms should have sputum and blood cultures drawn to help narrow antibiotics if negative.
HAP/ VAP² – HAP is defined as pneumonia that is not associated with mechanical ventilation that occurs > 48h after admission. VAP is defined as pneumonia occurring > 48h after intubation. These patients are at high risk of colonization and infection with MDR pathogens such as MRSA and Pseudomonas. Noninvasive respiratory cultures should be obtained to help guide antibiotic therapy.
- Empiric coverage of MRSA with IV vancomycin (or linezolid) is recommended in patients with risk factors. In HAP, risk factors include prior IV antibiotic use within 90 days, hospitalization in a unit where > 20% S. aureus isolates are MRSA, or are at high risk of mortality (septic shock, requiring ventilatory support). In VAP, empiric therapy is suggested only for patients in units where MRSA prevalence is >10-20% or prevalence is not known.
  - Sensitivity of negative MRSA nares swab for predicting MRSA pneumonia varies based on local prevalence. In low prevalence settings, a negative surveillance screen is reassuring. In high prevalence areas, a negative screen does not exclude MRSA pneumonia.
- Empiric therapy for Pseudomonas includes IV piperacillin-tazobactam/ cefepime/ ceftazidime/ aztreonam/ meropenem. The choice of which antipseudomonal agent should depend on local resistance patterns. In general, only 1 antipseudomonal agent is needed, but in rare cases where there is high resistance, double coverage for Pseudomonas should be added.
Aspiration pneumonia¹ – Aspiration pneumonia is common (5-15% of hospitalizations for pneumonia). Anaerobes were thought to play a major role in aspiration pneumonia, but new research suggests acute aspiration events in hospitalized patients are rarely associated with anaerobic infections. The new IDSA/ATS guidelines do not suggest routinely adding anaerobic coverage for aspiration pneumonia unless lung abscess or empyema is suspected.

Urinary Tract Infections: The IDSA/ESMID guidelines on acute uncomplicated cystitis and pyelonephritis are currently being updated so some of the following recommendations may change.

Acute simple cystitis³ – Uncomplicated/simple cystitis refers to a UTI limited to the bladder. E. coli accounts for 75-95% of all cases of uncomplicated cystitis and pyelonephritis. Other Enterobacteriaceae (such as Proteus, Klebsiella) and GPs such as S. saprophyticus make up the rest of common pathogens. Other organisms are rare.
- 1st line therapies: Nitrofurantoin 100 mg BID x 5 d OR Bactrim 160/800mg BID x 3 d (if local resistance rates do not exceed >20%) OR Fosfomycin 3 gm x 1.
  - Fosfomycin or nitrofurantoin should not be used in patients with suspected pyelonephritis.
- 2nd line therapies if the above options are not available or cannot be administered:
  - Urinary fluoroquinolones – ciprofloxacin, levofloxacin x 3 d. These are highly effective but are complicated by multiple side effects.
  - Amoxicillin-clavulanate, cefdinir, cefpodoxime x 3-7 d. Beta-lactams typically have lower efficacy and more side effects. Amoxicillin alone should not be used because of high prevalence of resistance.
- Though the 2011 IDSA/EMSID excluded men and women with urologic abnormalities or comorbidities (immunocompromise, poorly controlled diabetes), these patients may not necessary need to be treated as a complicated UTI. Closer observation of these patients may be needed with lower threshold to treat as complicated UTI. Kidney transplant patients are at risk of different complications and should be considered separately.^4,5
Acute complicated UTI⁶ – Complicated UTIs refer to UTIs that are associated with systemic symptoms (fever, chills, rigors) or extension beyond bladder (signs suggestive of pyelonephritis or prostatitis). E. coli is still the most common cause of complicated UTIs, but other organisms such as Klebsiella, Proteus, enterococci, Pseudomonas, staph (including MSSA/MRSA) can be seen depending on host risk factors (e.g., healthcare exposure). There is increasing prevalence of multidrug resistant (MDR) pathogens causing UTIs.
- Risk factors for MDR organisms include any of the following within the past 3 months: history of MDR organism; inpatient stay at healthcare facility (hospital, nursing home); use of fluoroquinolone/Bactrim/3rd generation cephalosporin or higher; travel to an area with high rates of MDR organisms.
- In patients who do not have risk factors for MDR organisms, IV ceftriaxone 1g daily is preferred. IV urinary fluoroquinolone or IV piperacillin-tazobactam are alternatives but offer broader coverage.
- In patients with risk factors or are critically ill, use IV piperacillin-tazobactam or IV meropenem. If the gram stain suggests a gram positive organism, IV vancomycin, daptomycin, or linezolid should be added.
CAUTI⁷ – CAUTI is defined by presence of symptoms or signs consistent with UTI, > 100k CFUs of 1 or more bacterial species on a urine specimen in a patient with an indwelling, suprapubic or intermittent catheterization. This includes patients who have had a catheter within the past 48 h.
- Diagnosis can be challenging since patients with indwelling catheters can be colonized with bacteria. In patients with short term catheterization, urine samples can be collected through the catheter port. However, in patients with long term indwelling catheters, a urine specimen off a freshly placed catheter is preferred.
- Microbiology in CAUTI also depends on the duration of catheterization.
  - Short term: E. coli is most common, but only accounts for 1/3 of isolates. Other Enterobacteriaceae (Klebsiella, Serratia, Citrobacter), Pseudomonas, and GPs such as CoNS, Entercoccus and Candida are also seen.
  - Long term (>2 weeks): Infections tend to be polymicrobial. Proteus is common in these settings.
  - The mnemonic SEEK PP can be helpful in identifying some common causes of UTIs.
- Empiric therapy should be based on whether a patient's infection is limited to the bladder (see acute simple cystitis and acute complicated cystitis above). Duration of therapy is typically 7-14 d.

Skin and Soft Tissue Infections (SSTI): This section reviews cellulitis and necrotizing soft tissue infections (NSTI). They are broadly classified as purulent and nonpurulent infections. Of note, different host factors (immunocompromise, diabetes, cirrhosis) and circumstances (bite wound, surgical site) alters the microbiology of skin and soft tissue infections.

Nonpurulent SSTI^8,9: Nonpurulent infections include cellulitis or erysipelas and are overwhelmingly caused by streptococci (most often group A, but can also be from other groups). MSSA is another cause of cellulitis, but is much less common. There is no role for superficial wound cultures in cellulitis.
- Empiric therapy should target Strep and MSSA. Outpatient therapy is most common with cephalexin. Inpatient therapy is typically with IV cefazolin or ceftriaxone.
- However, in patients with immunocompromise, rapid progression of cellulitis (concerning for possible NSTI), hypotension/shock, broader coverage with IV vancomycin AND piperacillin-tazobactam/ meropenem should be considered.^8,9
- In patients with shock, have high suspicion for streptococcal toxic shock syndrome. These patients should receive pen G and clindamycin.⁹
Purulent SSTI^8,9: Purulent infections include abscesses (with or without surrounding cellulitis), carbuncles, and furuncles. S. aureus, either MSSA (17%) or MRSA (59%), is the major cause of purulent infections.⁹ Depending on the location of the abscess, they may be polymicrobial. Peri-mucosal abscesses (peri-oral, peri-rectal, peri-vaginal) often include GAS, GNRs, anaerobes.¹⁰
- Treatment of purulent infections is primarily with incision and drainage. Unlike with nonpurulent SSTIs, gram stain and cultures should be sent of the purulent fluid. Empiric antibiotics should be have activity against MRSA. Additional coverage for Strep is typically not necessary, though can be considered in patients with high risk of adverse outcome (high risk of endocarditis, prosthetic materials, etc).¹¹
- Oral antibiotics with MRSA coverage include clindamycin, Bactrim, and doxycycline. The choice of antibiotic should be based on local MRSA sensitivities. There is high Strep resistance to Bactrim and doxycycline.¹¹
- In patients with signs of systemic illness or are admitted, IV vancomycin is first line. Daptomycin and linezolid can also be considered. Both these agents have activity against Strep.^9.11
NSTI^8,9.12: NSTIs involve the fascia and/or muscle compartments and are associated with high mortality. It should be suspected in patients with signs of systemic toxicity, rapid progression of cellulitis. Exam may reveal “woody” edema, crepitus/ gas on imaging, tenderness extending beyond area of erythema, bullae, skin necrosis. Some scoring systems (e.g., LRINEC score) can be helpful in diagnosis, but are no substitute for clinical judgement. Definitive diagnosis is made on surgical inspection.
- Microbiology can either be monomicrobial (GAS > S. aureus, GNRs, Clostridium) or polymicrobial (including a mix of aerobes and anaerobes). Polymicrobial infections are more common in perianal abscess/ surgical procedures involving the bowels, decubitus ulcers, injection sites in IVDU, spread from urogenital site.^8,12
- Treatment should involve urgent surgical consultation. Empiric antibiotic therapy should cover MRSA, GNRs, and anaerobes. Possible regimens include IV Vancomycin and piperacillin-tazobactam / meropenem. Addition of clindamycin provides antitoxin activity.

Intraabdominal Infections (IAI)¹³: Intraabdominal infections can be separated into community-acquired and hospital-acquired infections. Antimicrobial management of IAIs should be paired with source control.

Community acquired IAI: Microbiology of is typically of enteric organisms – primarily enteric GNRs (Enterobacteriaceae) and enteric anaerobes (Bacteroides). Enterococcus and Pseudomonas are not common in community acquired infections. Patients can be further stratefied into high risk or low risk.
- Risk factors include (but are not limited to) advanced age > 70, underlying comorbidities (heart, liver, renal disease, malignancy), delayed or inability to obtain source control.
- Low risk patients should receive empiric therapy should be with a third generation cephalosporin + metronidazole. A fluoroquinolone + metronidazole is an acceptable alternative but should be reserved for lower risk adults because of the high rates of E. coli resistance.
- IV piperacillin-tazobactam can be used in higher risk patients. Even though ampicillin-sulbactam would theoretically cover the spectrum of organisms, its use is not recommended because of high rates of E. coli resistance.
Hospital acquired IAI – Patients are considered to have health care or hospital acquired IAI if the infection develops > 48 h after initial source control; recent hospitalization for more than 48 h or residence in a nursing facility within past 90 d; use of broad spectrum therapy for > 5 d during the preceding 90 d; or home infusion/wound care/dialysis within the past 30 d.
- Microbiology in hospital or healthcare associated infections include enteric flora, but the incidence of Pseudomonas and Enterococcus is much more prevalent. Other resistant GNRs such as Acinetobacter, CoNS and S. aureus can also be seen.
- Empiric therapy should additionally cover Pseudomonas, Enterococcus. Patients with risk factors Enterococcus or MRSA should additionally be covered with Vancomycin. Patients with a history of VRE should receive daptomycin or linezolid.

Cases: These can be done selectively based on the content covered in your talk.

Case 1 – pneumonia
Case 2 – SSTI
Case 3 – intraabdominal infections
Case 4 – a is pneumonia; b is UTI
Case 5 – SSTI

Handout(s)

Sites of Infection Handout (for learners)

Presentation Board

Take Home Points

In general, health care associated infections are associated with MRSA, Pseudomonas, and Enterococcus.
CAP is most commonly caused by S. pneumoniae, GNRs, and atypical organisms. HAP (onset >48 h after hospitalization) is additionally associated with risk of MRSA and Pseudomonas.
Aspiration pneumonia and patients formerly classified as healthcare associated pneumonia should generally be treated with routine CAP treatment with notable exceptions.
CAUTIs are symptomatic bacteriuria associated with suprapubic, indwelling, or intermittent catheterization within the past 48 h. In addition to E. coli and other Enterobacteriaceae that cause non-CAUTIs, S. aureus, Pseudomonas, and Enteroccocus are common pathogens.
Strep is the most common cause of non-purulent SSTIs. S. aureus, namely MRSA, is the most common cause of purulent SSTIs.
Community acquired IAI are predominantly a result of intraabdominal streptococci, GNRs, and gut anaerobes. Hospital acquired infections are additionally associated with Pseudomonas, Enterococcus, and to a lesser degree MRSA.

References

Metlay J, et al. Diagnosis and Treatment of Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Disease Society of America. American Journal of Respiratory and Critical Care Medicine. 2019. 200(7): e45-e67
Kalil AC, et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of American and the American Thoracic Society. Clinical Infectious Disease. 2016; 65(8):e61-e111.
Gupta K, et al. International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women: A 2010 Update by the Infectious Diseases Society of American and European Society for Microbiology and Infectious Diseases. Clinical Infectious Disease. 2011; 52(5):e103-e120.
Hooton TM. Acute simple cystitis in men. In Uptodate, Calderwood SB (ed). UpToDate, Waltham, MA. (Accessed on September 20, 2021.)
Hooton TM & Gupta K. Acute simple cystitis in women. In Uptodate, Calderwood SB (ed). UpToDate, Waltham, MA. (Accessed on September 20, 2021.)
Hooton TM & Gupta K. Acute complicated urinary tract infection (including pyelonephritis) in adults. In Uptodate, Calderwood SB (ed). UpToDate, Waltham, MA. (Accessed on September 20, 2021.)
Hooton TM, et al. Diagnosis, Prevention, and Treatment of Catheter-Associated Urinary Tract Infection in Adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clinical Infectious Diseases. 2010; 50(5):625-663.
Stevens DL, et al. Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases of Society of America. Clinical Infectious Diseases. 2014; 52(2):e10-52.
Raff AB & Kronshinksy D. Cellulitis: A Review. JAMA. 2016;316(3):325-337.
Spelman D & Baddour LM. Cellulitis and skin abscess: Epidemiology, microbiology, clinical manifestations, and diagnosis. In Uptodate, Lowy FD & Kaplan SL (eds). UpToDate, Waltham, MA. (Accessed on September 21, 2021.)
Spelman D & Baddour LM. Cellulitis and skin abscess in adults: Treatment. In Uptodate, Lowy FD & Kaplan SL (eds). UpToDate, Waltham, MA. (Accessed on September 21, 2021.)
Stevens DL, Bryan AE, & Goldstein EJC. Necrotizing Soft Tissue Infections. Infect Dis Clin N Am. 2021; 35: 135-155.
Mazuski JE, et al. The Surgical Infection Society Revised Guideliens on the Manaement of Intraabdominal Infection. Surgical Infections. 2017; 18(1): http://doi.org/10.1089/sur.2016.261

Antibiotics Part 2: Sites of Infection

Table of Contents

Table of Contents

Objective(s)

Teaching Instructions

Handout(s)

Presentation Board

Take Home Points

References

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