ANTIBIOTIC
ESSENTIALS
Fourteenth Edition
Edited by
Burke A. Cunha, MD, MACP
Chief, Infectious Disease Division
Winthrop-University Hospital
Mineola, New York
Professor of Medicine
State University of New York
School of Medicine
Stony Brook, New York
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Antibiotic Essentials
Fourteenth Edition: 2015
ISBN 978-93-5152-850-0
Printed at
ABOUT THE EDITOR
Burke A. Cunha, MD, MACP, is Chief, Infectious Disease Division at Winthrop-University
Hospital, Mineola, New York; Professor of Medicine, State University of New York School of
Medicine, Stony Brook, New York; and is one of the world’s leading authorities on infectious
diseases. During his career, he has written/edited over 1250 articles, 200 book chapters, and 30
books on infectious diseases. He has received numerous teaching awards, including the
Aesculapius Award for teaching excellence and the Spatz Award for clinical excellence
and teaching excellence. Dr. Cunha is a Fellow of the Infectious Disease Society of America,
American Academy of Microbiology, American College of Clinical Pharmacology, Surgical Infection
Society, American College of Chest Physicians and Society of Hospital Epidemiologists of America.
He has had a long interest in clinical syndromic diagnosis, diagnostic reasoning, antimicrobial
therapy and resistance, atypical pneumonias, surgical infections, infections in compromised hosts,
zoonoses, FUOs, meningitis and encephalitis, endocarditis, and nosocomial infections. Dr. Cunha
is a Master of the American College of Physicians, awarded for lifetime achievement as a Master
Clinician and Master Teacher of Infectious Diseases.
DEDICATION
for
Marie
“Grace in her steps,
Heaven in her eye,
In every gesture, dignity and love”
Milton
iv
Antibiotic Essentials
TABLE OF CONTENTS
1. VERVIEW OF ANTIMICROBIAL
O
THERAPY
1
Factors in Antibiotic Selection....................................2
Spectrum.............................................................................2
Tissue Penetration.........................................................2
Antibiotic Resistance...................................................2
Safety Profile......................................................................4
Cost.........................................................................................4
Factors in Antibiotic Dosing.........................................4
Dosing in Renal/Hepatic Insufficiency.............5
Routes of Elimination (Renal and Hepatic)....5
Microbiology and Susceptibility Testing..............6
In Vitro vs. In Vivo Susceptibility............................7
PK/PD and Other Considerations in
Antimicrobial Therapy.....................................................9
Bactericidal vs. Bacteriostatic Therapy..............9
Monotherapy vs. Combination Therapy..........9
Intravenous vs. Oral Switch Therapy............... 10
Bioavailability of Oral Antibiotics....................... 11
OPAT.................................................................................... 11
Duration of Therapy.................................................. 11
Empiric vs. Specific Antibiotic Therapy ............. 12
Positive Blood Cultures vs. Bacteremia
(MSSA, MRSA, CoNS)................................................. 13
Drug Fever............................................................................ 13
Relative Bradycardia....................................................... 14
Antibiotic Failure.............................................................. 14
Pitfalls in Antibiotic Prescribing............................... 15
2. MPIRIC THERAPY BASED ON CLINICAL
E
SYNDROME
17
CNS Infections
Acute Bacterial Meningitis......................................... 18
Acute Nonbacterial/Chronic Meningitis........... 21
Encephalitis......................................................................... 25
Brain Abscess/Subdural Empyema/
Cavernous Vein Thrombosis/Intracranial
Suppurative Thrombophlebitis.......................... 27
HEENT Infections
Facial/Periorbital Cellulitis........................................... 29
Bacterial Sinusitis.............................................................. 30
Keratitis................................................................................... 31
Conjunctivitis...................................................................... 32
Chorioretinitis..................................................................... 34
Endophthalmitis............................................................... 35
External Otitis..................................................................... 37
Acute Otitis Media........................................................... 38
Mastoiditis............................................................................ 39
Suppurative Parotitis...................................................... 40
Pharyngitis............................................................................ 40
Thrush (Oropharyngeal Candidiasis)................... 43
Mouth Ulcers/Vesicles.................................................. 44
Deep Neck Infections, Lemierre’s
Syndrome, Severe Dental Infections.............. 46
Epiglottitis............................................................................. 47
Lower Respiratory Tract Infections
Acute Bacterial Exacerbation of
Chronic Bronchitis........................................................ 48
Mediastinitis........................................................................ 49
Community-Acquired Pneumonia....................... 49
Zoonotic Atypical Pneumonia................................. 60
Lung Abscess/Empyema............................................ 67
Nursing Home-Acquired Pneumonia................. 68
Nosocomial Pneumonia.............................................. 68
Cardiovascular Infections
Subacute Bacterial Endocarditis............................. 70
Acute Bacterial Endocarditis..................................... 74
Prosthetic Valve Endocarditis................................... 76
Pericarditis/Myocarditis................................................ 78
Central IV Line/Pacemaker Infections................. 79
Vascular Graft Infections.............................................. 82
Gastrointestinal Tract Infections
Esophagitis........................................................................... 84
Peptic Ulcer Disease....................................................... 85
Gastric Perforation........................................................... 85
Diarrhea/Typhoid (Enteric) Fever.............................. 86
Cholecystitis........................................................................ 92
Cholangitis........................................................................... 93
Gallbladder Wall Abscess/Perforation................. 93
Acute Pancreatitis............................................................ 94
Pancreatic Abscess/Infected Pancreatic
P
seudocyst..................................................................... 95
Liver Abscess...................................................................... 95
Hepatosplenic Candidiasis......................................... 96
Granulomatous Hepatitis............................................ 96
Viral Hepatitis...................................................................... 97
Intraabdominal or Pelvic Peritonitis/
Abscess (Colitis, Appendicitis,
D
iverticulitis, Septic Pelvic
Thrombophlebitis, Spontaneous
B
acterial Peritonitis, CAPD-Associated
P
eritonitis, TB Peritonitis)..................................... 100
Table of Contents
Genitourinary Tract Infections
Dysuria-Pyuria Syndrome........................................ 103
Cystitis.................................................................................. 103
Catheter-Associated Bacteriuria/Candiduria........104
Epididymitis...................................................................... 106
Acute Pyelonephritis................................................... 107
Chronic Pyelonephritis.............................................. 108
Renal TB............................................................................... 108
Renal Abscess (Intrarenal/Perinephric)........... 109
Prostatitis/Prostatic Abscess................................... 110
Urosepsis............................................................................ 111
Pelvic Inflammatory Disease, Salpingitis,
T
uboovarian Abscess, Endometritis/
Endomyometritis, Septic Abortion............... 113
Sexually Transmitted Diseases
Urethritis/Cervicitis........................................................ 114
Vaginitis/Balanitis............................................................ 115
Genital Vesicles................................................................. 116
Genital Ulcers.................................................................... 117
Suppurating Inguinal Adenopathy..................... 118
Genital/Perianal Warts................................................. 118
Syphilis................................................................................... 119
Bone and Joint Infections
Septic Arthritis/Bursitis................................................ 121
Lyme Disease/Lyme Arthritis................................... 127
Infected Joint Prosthesis............................................ 128
Osteomyelitis..................................................................... 129
Skin and Soft Tissue Infections
Cellulitis, Erysipelas, Mastitis.................................... 132
Complicated Skin/Skin Structure
Infections (cSSSIs)...................................................... 134
Skin Ulcers........................................................................... 137
Skin Abscesses/Infected Cysts (Skin
Pustules/Boils, Furunculosis).............................. 140
Skin Vesicles (Non-Genital)....................................... 142
Wound Infections........................................................... 144
Superficial Fungal Infections Skin/Nail.............. 147
Skin Infestations............................................................... 150
Ischiorectal/Perirectal Abscess............................... 151
Sepsis/Septic Shock
151
Febrile Neutropenia
158
Transplant Infections
Bacteremia.......................................................................... 160
Candidemia........................................................................ 161
CMV/HHV-6/BK Virus..................................................... 162
EVB/PTLD............................................................................. 163
RSV........................................................................................... 163
Adenovirus.......................................................................... 163
Encephalitis/Meningitis.............................................. 164
v
Brain Abscess/Mass Lesions..................................... 164
Focal/Segmental Pulmonary
Infiltrates......................................................................... 165
Diffuse Pulmonary Infiltrates................................... 165
Viral Hepatitis..................................................................... 166
Toxin-Mediated Infectious Diseases
Toxic Shock Syndrome................................................ 169
Botulism................................................................................ 170
Tetanus.................................................................................. 170
Diphtheria........................................................................... 170
Bioterrorist Agents
Anthrax.................................................................................. 173
Tularemia Pneumonia.................................................. 173
Pneumonic Plague......................................................... 174
Botulism................................................................................ 174
Smallpox............................................................................... 174
Ebola....................................................................................... 174
3. ANTIBIOTIC SUSCEPTIBILITY PROFILES
AND INITIAL THERAPY OF ISOLATES
PENDING SUSCEPTIBILITY RESULTS
185
Antibiotic Susceptibility Profiles (Penicillins,
Macrolides, Tetracyclines, and Others)......... 186
Antibiotic Susceptibility Profiles
(Cephalosporins)........................................................ 191
Antibiotic Susceptibility Profiles
(Aminoglycosides, Fluoroquinolones,
Carbapenems, and Others)................................. 198
Gram Stain Characteristics of Isolates (by
Morphology Arrangement,
Oxygen Requirements).......................................... 203
Alphabetical Index of Isolates................................. 205
Key Factors in Antibiotic Selection (Isolate
Known)............................................................................. 207
Antibiotic Resistance Potential............................... 207
Aerobic Isolates................................................................ 208
Capnophilic Isolates...................................................... 235
Anaerobic Isolates.......................................................... 236
Yeast/Fungi......................................................................... 242
Gram Stain/Giemsa Stain Technique.................. 246
CSF Gram Stain................................................................. 246
Sputum Gram Stain....................................................... 248
Urine Gram Stain............................................................. 248
Fecal Gram Stain.............................................................. 249
4. PARASITES, FUNGI, UNUSUAL
ORGANISMS
253
Blood Pathogens
Microfilaria in Blood...................................................... 254
Trypanosomes in Blood.............................................. 255
Spirochetes in Blood..................................................... 257
Intracellular Inclusion Bodies in Blood.............. 258
vi
Antibiotic Essentials
CSF/Brain Pathogens
Cysts/Mass Lesions in CSF/Brain............................ 261
Lung Pathogens
Pulmonary Cystic Lesions/Masses........................ 265
Pulmonary Coin Lesions............................................. 266
Pulmonary Infiltrates/Mass Lesions..................... 267
Heart Pathogens
Chagas’ Disease................................................................ 273
Liver Pathogens
Liver Flukes.......................................................................... 273
Cystic Masses in Liver................................................... 274
Hepatomegaly.................................................................. 275
Stool/Intestines Pathogens
Intestinal Protozoa......................................................... 276
Intestinal Nematodes (Roundworms)................ 278
Intestinal Cestodes (Tapeworms)......................... 281
Intestinal Trematodes
(Flukes/Flatworms)................................................... 282
Other Intestinal Infections......................................... 282
Skin/Muscle Pathogens
Infiltrative Skin/ ubcutaneous Lesions........... 283
S
Infiltrative Skin Lesions ± Ulcers/Sinus
Tracts/Abscesses...................................................... 284
Skin Vesicles/Bullae...................................................... 288
Subcutaneous Serpiginous Lesions.................. 288
Skin Papules/Nodules/Abscesses....................... 289
Rickettsia (Fever/Petechial Skin Rash).............. 294
Other Skin Lesions........................................................ 297
Myositis............................................................................... 298
5. HIV INFECTION
301
Overview ........................................................................... 302
Stages of HIV Infection.............................................. 303
Acute (Primary) HIV Infection................................ 304
Approach to HIV Testing........................................... 305
Initial Assessment of HIV Patients...............................308
Indications for Treatment of HIV
Infection........................................................................ 312
Antiretroviral Treatment............................................ 313
Antiretroviral Treatment Failure............................ 316
Opportunistic Infections in HIV Disease......... 319
Treatment of Opportunistic Infections............ 323
Treatment of Other Opportunistic
Infections in HIV........................................................ 338
HIV Coinfections (HBV/HCV).................................. 344
6. PROPHYLAXIS AND
IMMUNIZATIONS
353
Surgical Prophylaxis..................................................... 354
Post-Exposure Prophylaxis...................................... 358
Chronic Medical Prophylaxis/Suppression..........364
HIV Pre-Exposure Prophylaxis (PrEP).........................365
HIV Post-Exposure Prophylaxis (PEP)........................366
HIV Opportunistic Infections..........................................366
Transplant Prophylaxis........................................................367
Endocarditis Prophylaxis........................................... 369
Travel Prophylaxis.......................................................... 371
Malaria Prophylaxis...................................................... 375
Tetanus Prophylaxis..................................................... 377
Immunizations................................................................ 378
7. EDIATRIC INFECTIOUS DISEASES
P
AND PEDIATRIC DRUG
SUMMARIES
386
CNS Infections............................................................... 387
HEENT Infections......................................................... 391
Lower Respiratory Tract Infections................... 396
Vascular Infections...................................................... 402
Gastrointestinal Infections..................................... 403
Bone and Joint Infections...................................... 407
Skin and Soft Tissue Infections............................ 411
Common Pediatric Antimicrobial Drugs........414
8. CHEST X-RAY ATLAS
425
Unilateral Focal Segmental/Lobar Infiltrate
Without Effusion.....................................................................426
Unilateral Focal Segmental/Lobar
Infiltrate With Effusion........................................ 431
Unilateral Ill-Defined Infiltrates Without
Effusion ....................................................................... 436
Unilateral Ill-Defined Infiltrates With
Effusion ..................................................................................443
Bilateral Infiltrates Without Effusion ................ 448
Bilateral Infiltrates With Effusion ....................... 458
Cavitary Infiltrates (Thick-Walled) ..................... 463
Cavitary Infiltrates (Thin-Walled) ...................... 470
9. INFECTIOUS DISEASE DIFFERENTIAL
DIAGNOSIS
474
10. ANTIBIOTIC PEARLS & PITFALLS 507
11. ANTIMICROBIAL DRUG SUMMARIES
521
APPENDIX
720
INDEX
731
COLOR ATLAS OF CSF, SPUTUM, AND
URINE GRAM STAINS & FUNGAL STAINS
vii
EDITORS
Burke A. Cunha, MD, MACP
Editor
Cheston B. Cunha, MD
Associate Editor
CONTRIBUTORS
Burke A. Cunha, MD, MACP
Chief, Infectious Disease Division
Winthrop-University Hospital
Mineola, New York
Professor of Medicine
State University of New York
School of Medicine
Stony Brook, New York
All chapters except HIV Infection &
Pediatric ID
Jeffrey Baron, PharmD
Clinical Pharmacist
Winthrop-University Hospital
Mineola, New York
HBV, HCV, and HIV Guidelines
Antimicrobial Drug Summaries
Edward J. Bottone, PhD
Professor of Medicine
Professor of Microbiology
Professor of Pathology
Mount Sinai
School of Medicine
New York, New York
Medical Microbiology; Parasites,
Fungi, Unusual Organisms
John L. Brusch, MD
Associate Chief of Medicine
Cambridge Health Alliance
Infectious Disease Service
Cambridge Health Alliance
Medical Director, Somerville Hospital
Assistant Professor of Medicine
Harvard Medical School
Boston, Massachusetts
Endocarditis: Therapy & Prophylaxis
Cheston B. Cunha, MD
Director, Antibiotic Stewardship Program
Rhode Island Hospital and The Miriam Hospital
Infectious Disease Division
Assistant Professor of Medicine
Brown University Alpert School of Medicine
Providence, Rhode Island
Infectious Disease Differential Diagnosis
Overview of Antimicrobial Therapy
Empiric Therapy Based of Clinical Syndromes
Antimicrobial Drug Summaries
Daniel Caplivski, MD
Infectious Disease Division
Assistant Professor of Medicine
Mt. Sinai School of Medicine
New York, New York
Fungal Stain Atlas
Dennis J. Cleri, MD
St. Francis Medical Center
Professor of Medicine
Seton Hall University
School of Graduate Medical Education
Trenton, New Jersey
Bioterrorism
Staci A. Fischer, MD
Director, Transplant Infectious Diseases
Rhode Island Hospital
Infectious Disease Division
Associate Professor of Medicine
Brown University Alpert School of Medicine
Providence, Rhode Island
Transplant Infections: Therapy & Prophylaxis
viii
Antibiotic Essentials
Pierce Gardner, MD
Senior Advisor, Clinical Research and Training
National Institutes of Health
John E. Fogarty International Center for
Advanced Study in the Health Sciences
Bethesda, Maryland
Prophylaxis and Immunization
Arthur Gran, MD
Infectious Disease Division
Winthrop-University Hospital
Mineola, New York
State University of New York
School of Medicine
Stony Brook, New York
Antimicrobial Drug Summaries
Jean E. Hage, MD
Infectious Disease Division
Winthrop-University Hospital
Mineola, New York
State University of New York
School of Medicine
Stony Brook, New York
Empiric Therapy of Clinical Syndromes;
Prophylaxis & Immunization;
Parasitic & Fungi; Unusual Organisms;
Antimicrobial Drug Summaries
Mark H. Kaplan, MD
Professor of Medicine
Infectious Diseases
University of Michigan School of Medicine
Ann Arbor, Michigan
HIV Drug Summaries
Douglas S. Katz, MD
Vice Chairman, Clinical Research and Education
Director, Body CT
Winthrop-University Hospital
Mineola, New York
Professor of Clinical Radiology
State University of New York School of edicine
M
Stony Brook, New York
Chest X-ray Atlas
Raymond S. Koff, MD
Clinical Professor of Medicine
University of Connecticut School of Medicine
Farmington, Connecticut
Viral Hepatitis: Therapy & Prophylaxis
Leonard R. Krilov, MD
Chief, Pediatric Infectious Disease Division
Winthrop-University Hospital
Mineola, New York
Professor of Pediatrics
State University of New York
School of Medicine
Stony Brook, New York
Pediatric Infectious Diseases
David W. Kubiak, PharmD
Infectious Disease Clinical Pharmacist
Brigham and Women’s Hospital
Boston, Massachusetts
Antiretroviral Drug Summaries
Brian R Malone, BS, MS, RPh
Director, Pharmaceutical Services
Winthrop-University Hospital
Mineola, New York
Adjunct Affiliate Professor
College of Pharmacy St. John’s University
Queens, New York
Pediatric Drug Summaries
George H. McCracken, Jr., MD
Distinguished Professor of Pediatric Infectious
Disease and the Sarah M. and Charles E. Seay
Chair in Pediatric Infectious Disease
University of Texas Southwestern Medical Center
Dallas, Texas
Pediatric Infectious Diseases
James H. McGuire, MD
Master Clinician
Division of Infectious Diseases
Brigham and Women’s Hospital
Professor of Medicine
Harvard Medical School
Boston, Massachusetts
Parasites, Fungi, Unusual Organisms
Nardeen Mickail, MD
Infectious Disease Division
Winthrop-University Hospital
Mineola, New York
State University of New York
School of Medicine, Stony Brook, New York
Antimicrobial Drug Summaries
Contributors ix
Maria D. Mileno, MD
Michael F. Rein, MD
Director, Travel Medicine
The Miriam Hospital
Infectious Disease Division
Associate Professor of Medicine
Brown University Alpert School of Medicine
Providence, Rhode Island
Prophylaxis and Immunizations
Professor of Medicine (Emeritus)
University of Virginia Health System
Charlottesville, Virginia
Sexually Transmitted Diseases
Robert Moore, MD
Chairman, Department of Radiology
Stony Brook University Hospital
Professor of Radiology
State University of New York School of Medicine
Stony Brook, New York
Chest X-ray Atlas
Sigridh Muñoz-Gomez, MD
John H. Rex, MD
Adjunct Professor of Medicine
University of Texas Medical School
Houston, Texas
Vice-President
Medical Director for Infection
AstraZeneca Pharmaceuticals
Macclesfield, UK
Antifungal Therapy
Paul E. Sax, MD
Infectious Disease Division
Winthrop-University Hospital
Mineola, New York
State University of New York
School of Medicine
Stony Brook, New York
Antimicrobial Drug Summaries
Clinical Director
Division of Infectious Diseases and HIV
Division of Infectious Diseases
Brigham and Women’s Hospital
Associate Professor of Medicine
Harvard Medical School
Boston, Massachusetts
HIV Infection
Ronald L. Nichols, MD
David Schlossberg, MD
William Henderson Professor of Surgery
Professor of Microbiology and Immunology
Tulane University School of Medicine
New Orleans, Louisiana
Surgical Prophylaxis and Therapy
Genovefa Papanicolaou, MD
Attending Physician, Infectious Disease Service
Memorial Sloan Kettering Cancer Center
Associate Professor of Medicine
Weill Cornell Medical College
New York, New York
Transplant Infections: Therapy & Prophylaxis
Muhammed Raza, MBBS
Infectious Disease Division
Winthrop-University Hospital
Mineola, New York
State University of New York
School of Medicine
Stony Brook, New York
Antimicrobial Drug Summaries
Tuberculosis Control Program
Philadelphia Department of Health
Professor of Medicine
Temple University School of Medicine
Philadelphia, Pennsylvania
Tuberculosis
Paul E. Schoch, PhD
Director
Clinical Microbiology Laboratory
Winthrop-University Hospital
Mineola, New York
Medical Microbiology and Gram
Stains Atlas
Daniel S. Siegal, MD
Department of Radiology
Mount Auburn Hospital
Harvard Medical School
Boston, Massachusetts
Chest X-ray Atlas
x
Antibiotic Essentials
Stephanie Strollo, MD
Infectious Disease Division
Winthrop-University Hospital
Mineola, New York
State University of New York
School of Medicine
Stony Brook, New York
Initial Therapy of Isolates Pending
Susceptibility Testing
Uzma Syed, DO
Infectious Disease Division
Winthrop-University Hospital
Mineola, New York
State University of New York
School of Medicine
Stony Brook, New York
Initial Therapy of Isolates Pending
Susceptibility Testing
Damary C. Torres, PharmD
Clinical Pharmacy Specialist
Winthrop-University Hospital
Mineola, New York
Associate Clinical Professor
College of Pharmacy St. John’s University
Queens, New York
Antimicrobial Drug Summaries
Kenneth F. Wagner, DO
Infectious Disease Consultant
National Naval Medical Center
Associate Professor of Medicine
Uniformed Services, University of
the Health Sciences
F. Edward Hebert School of Medicine
Bethesda, Maryland
Parasites, Fungi, Unusual Organisms
xi
ACKNOWLEDGMENTS
I would like to thank the many contributors who graciously contributed their time and energy;
and especially Mark Freed, MD, past President and Editor-in-Chief of Physicians’ Press, for his vision,
commitment, and guidance.
Burke A. Cunha, MD
NOTICE
The clinical recommendations set forth in this book are those of the authors and are offered as
general guidelines, not specific instructions for individual patients. Clinical judgement should
always guide the physician in the selection, dosing, and duration of antimicrobial therapy for
individual patients.
Not all recommendations in this book are approved indications by the U.S. Food and
Drug Administration, and antimicrobial recommendations are not limited to indications in
the package insert. The use of any drug should be preceded by careful review of the package insert, which provides indications and dosing approved by the U.S. Food and Drug
Administration.
The information provided in this book is essential not exhaustive, and the reader is referred to
other medical references and the manufacturer’s product literature for further information. Clinical
use of the information provided and any consequences that may arise from its use is the responsibility of
the prescribing physician. The authors, editors, and publisher do not warrant or guarantee the information herein contained and do not assume and expressly disclaim any liability for errors or omissions or
any consequences that may occur from use of this information.
BASIS OF RECOMMENDATIONS
The therapeutic recommendations in Antibiotic Essentials are based on the contributors’
clinical expertise and experience as well as the literature and clinical guidelines.
xii
Antibiotic Essentials
ABBREVIATIONS
ABE
ABM
ADA
AFB
AIH
AIHA
AML
ANA
ARDS
AG
A-V
β-lactams
BAL
BG
BMT
BPH
CAB
CABG
CAC
CAH
CA-MRSA
CAP
CD4
CE
CFS
CGD
CIE
CLL
CML
CMV
CNS
CO-MRSA
CoNS
CPH
CPK
CrCl
CRE
CSD
CSF
CT
CVA
CVC
CVID
CVVH
CXR
DFA
acute bacterial endocarditis
acute bacterial meningitis
adenosine deaminase
acid fast bacilli
autoimmune lupoid hepatitis
autoimmune hemolytic anemia
acute myelogenous leukemia
antinuclear antibody
adult respiratory distress syndrome
Aspergillus galactomannan
atrio-ventricular
penicillins, cephalosporins,
cephamycins (not monobactams or
carbapenems)
bronchoalveolar lavage
b 1, 3 D-glucan
bone marrow transplant
benign prostatic hypertrophy
catheter associated bacteriuria
coronary artery bypass grafting
catheter associated candiduria
chronic active hepatitis
community-acquired MRSA
community-acquired pneumonia
CD4 T-cell lymphocyte
California encephalitis virus
chronic fatigue syndrome
chronic granulomatous disease
counter-immunoelectrophoresis
chronic lymphocytic leukemia
chronic myelogenous leukemia
Cytomegalovirus
central nervous system
community onset MRSA
coagulase negative staphylococci
chronic persistent hepatitis
creatine phosphokinase
creatinine clearance
carbapenemase resistant
Enterobacteriaceae
cat scratch disease
cerebrospinal fluid
computerized tomography
costovertebral angle
central venous catheter
common variable immune deficiency
continuous veno venous
hemo filtration
chest x-ray
direct fluorescent antibody
DI
diabetes insipidus
DIC
disseminated intravascular coagulation
DM
diabetes mellitus
DOT
directly observed therapy
e.g.
for example
EBV
Ebstein-Barr virus
EEE
Eastern equine encephalitis
EEG
electroencephalogram
EIA
enzyme immunoassay
ELISA
enzyme-linked immunosorbent assay
EM
erythema migrans
EMB
ethambutol
Enterobacteriaceae: Citrobacter, Edwardsiella,
Enterobacter, E. coli, Klebsiella,
Proteus, Providencia, Shigella,
S
almonella, Serratia, Hafnia,
Morganella, Yersinia
ESBLs
extended spectrum β-lactamases
esp
especially
ESR
erythrocyte sedimentation rate
ESRD
end-stage renal disease
ET
endotracheal
EV
enterovirus
EVD
external ventricular drain
FTA-ABS
fluorescent treponemal
antibody absorption test
FUO
fever of unknown origin
G6PD
glucose-6-phosphate dehydrogenase
GC
gonococcus/gonorrhea
GCA
giant cell arteritis
GI
gastrointestinal
gm
gram
GU
genitourinary
GVHD
graft versus host disease
HA-MRSA
hospital acquired MRSA
HAP
hospital acquired pneumonia
HAV
hepatitis A virus
HBcAb
hepatitis B core antibody
HBoV
human bocavirus
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HD
hemodialysis
HDV
hepatitis D virus
HEV
hepatitis E virus
HFHD
high flux hemodialysis
HFV
hepatitis F virus
HFM
hand foot mouth disease
HGA
HHV-6,7,8
HME
hMPV
HPS
HPV
HTLV-1
HRIG
HSV
I&D
IFA
IgA
IgG
IgM
IM
INH
IP
IT
ITP
IV
IV/PO
IVDA
IVIG
JE
kg
L
LCM
LDH
LFTs
LGV
MAI
MCD
mcg
mcL
MDR
MDRSP
MERS
mg
mL
MIC
min
MMR
MPD
MRI
MRSA
MRSE
MS
MSSA
MSSE
MTT
MU
MVP
NDM
NHAP
Abbreviations xiii
human granulocytic anaplasmosis
human herpes virus 6,7,8
human monocytic ehrlichiosis
human metapneumovirus
Hanta virus pulmonary syndrome
human papilloma virus
human T-cell leukemia virus
human rabies immune globulin
herpes simplex virus
incision and drainage
immunofluorescent antibody
immunoglobulin A
immunoglobulin G
immunoglobulin M
intramuscular
isoniazid
intraperitoneal
intrathecal
idiopathic thrombocytopenic purpura
intravenous
IV or PO
intravenous drug abuser
intravenous immunoglobulin
Japanese encephalitis
kilogram
liter
lymphocytic choriomeningitis
lactate dehydrogenase
liver function tests
lymphogranuloma venereum
Mycobacterium avium-intracellulare
multicentric Castleman’s disease
microgram
microliter
multidrug resistant
multidrug resistant S. pneumoniae
middle east respiratory syndrome
milligram
milliliter
minimum inhibitory concentration
minute
measles, mumps, rubella
myeloprolifevative disorder
magnetic resonance imaging
methicillin-resistant S. aureus
methicillin-resistant S. epidermidis
multiple sclerosis
methicillin-sensitive S. aureus
methicillin-sensitive S. epidermidis
methlytetrathiazole
million units
mitral valve prolapse
New Delhi metallo-b-lactamase
nursing home acquired pneumonia
NNRTI
non-nucleoside reverse
transcriptase inhibitor
nosocomial pneumonia
nucleoside reverse
transcriptase inhibitor
NSAIDs
nonsteroidal anti-inflammatory drugs
OI
opportunistic infection
OPAT
outpatient parenteral antibiotic therapy
PAN
polyarteritis nodosa
PBC
primary biliary cirrhosis
PBS
protected brush specimen
PCEC
purified chick embryo cells
PCN
penicillin
PCP
Pneumocystis (carinii) jiroveci
pneumonia
PCR
polymerase chain reaction
PD
peritoneal dialysis
PDA
patent ductus arteriosus
PE
Powassan encephalitis
PEP
post-exposure prophylaxis
PI
protease inhibitor
PID
pelvic inflammatory disease
progressive multifocal leukoencephalopathy
PML
PMN
polymorphonuclear leucocytes
PO
oral
PPD
tuberculin skin test
PPIs
proton pump inhibitors
PPNG
penicillinase-producing N. gonorrhoeae
PTBM
partially treated bacterial meningitis
PVE
prosthetic valve endocarditis
PVL
Panton-Valentine leukocidin
PZA
pyrazinamide
q__d
every __ days
q__h
every __ hours
q month
once a month
q week
once a week
RA
rheumatoid arthritis
RBC
red blood cells
RE
regional ileitis (Crohn’s disease)
RMSF
rocky mountain spotted fever
RSV
respiratory syncytial virus
RUQ
right upper quadrant
RVA
rabies vaccine absorbed
SARS
severe acute respiratory syndrome
SBE
subacute bacterial endocarditis
SCID
severe combined immune deficiency
SGOT/SGPT serum transaminases
SLE
systemic lupus erythematosus
St. LE
Saint Louis encephalitis
SOT
solid organ transplant
sp.
species
SPB
spontaneous bacterial peritonitis
SPEP
serum protein electrophoresis
SQ
subcutaneous
STD
sexually transmitted diseases
TA
temporal arteritis
TAA
teichoic acid antibody titers
NP
NRTI
xiv
TAH/BSO
TB
TDF
TEE
TEN
TID
TMP
TMP–SMX
TPN
TRNG
TSS
TTE
TTP
TURP
UC
UTI
Antibiotic Essentials
total abdominal hysterectomy/bilateral
salpingoophorectomy
M. tuberculosis
tenofovir disoproxil fumarate
transesophageal echocardiogram
toxic epidermal necrolysis
three times per day
trimethoprim
trimethoprim-sulfamethoxazole
total parenteral nutrition
tetracycline-resistant N.gonorrhoeae
toxic shock syndrome
transthoracic echocardiogram
thrombotic thrombocytopenic purpura
transurethral resection of prostate
ulcerative colitis
urinary tract infection
VA
VAP
VCA
VEE
VISA
VLM
VP
VRE
VRSA
VSE
VZV
WBC
WEE
WNE
XMRV
yrs
ventriculoatrial
ventilator associated pneumonia
viral capsid antigen
Venezuelan equine encephalitis virus
vancomycin intermediate S. aureus
visceral larval migrans
ventriculoperitoneal
vancomycin resistant enterococci
vancomycin resistant S. aureus
vancomycin-sensitive enterococci
varicella zoster virus
white blood cells
western equine encephalitis
west nile encephalitis
xenotropic murine leukemia related virus
years
Chapter 1. Overview of Antimicrobial Therapy
1
Chapter 1
Overview of Antimicrobial Therapy
Burke A. Cunha, MD
Cheston B. Cunha, MD
Factors in Antibiotic Selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Spectrum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Tissue Penetration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Antibiotic Resistance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Factors in Antibiotic Dosing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Dosing in Renal/Hepatic Insufficiency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Routes of Elimination (Renal and Hepatic) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Microbiology and Susceptibility Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
In Vitro vs. In Vivo Susceptibility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Susceptibility Breakpoints for S. pneumoniae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
PK/PD and Other Considerations in Antimicrobial Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Bactericidal vs. Bacteriostatic Antibiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Monotherapy vs. Combination Therapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
IV to PO Switch Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Bioavailability of Oral Antibiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
OPAT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Duration of Antibiotic Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Empiric vs. Specific Antibiotic Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Positive Blood Cultures vs. Bacteremia (MSSA, MRSA, CoNS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Drug Fever . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Relative Bradycardia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
Antibiotic Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
Pitfalls in Antibiotic Prescribing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
References and Suggested Readings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
2
Antibiotic Essentials
Overview of Antimicrobial Therapy
FACTORS IN ANTIBIOTIC SELECTION
A. Spectrum. Antibiotic spectrum refers to the range of microorganisms an antibiotic is
usually effective against, and is the basis for empiric antibiotic therapy (Chapter 2). Antibiotic
susceptibilities are a guide to predicting antibotic effectiveness in blood/well vascularized
organs. In vitro testing does not always predict in vivo effectiveness (see p. 6).
B. Tissue Penetration. Antibiotics that are effective against a microorganism in vitro but
unable to reach the site of infection are of little or no benefit to the host. Antibiotic tissue
penetration depends on properties of the antibiotic, e.g., lipid solubility, molecular size and
tissue, e.g., adequacy of blood supply, presence of inflammation. Antibiotic tissue penetration
is rarely problematic in acute infections due to increased microvascular permeability from
local release of chemical inflammatory mediators. In contrast, chronic infections, e.g.,
chronic pyelonephritis, chronic prostatitis, chronic osteomyelitis and infections caused
by intracellular pathogens often rely on chemical properties of an antibiotic, e.g., high
lipid solubility, small molecular size for adequate tissue penetration. Antibiotics cannot be
expected to eradicate organisms from areas that are difficult to penetrate or have impaired
blood supply, such as abscesses, which usually require surgical drainage for cure. In addition,
implanted foreign materials associated with infection usually need to be removed for cure,
since microbes causing infections associated with prosthetic joints, shunts, and intravenous
lines produce a slime/biofilm on plastic/metal surfaces that permits organisms to survive
despite antimicrobial therapy.
C. Antibiotic Resistance. Bacterial resistance to antimicrobial therapy may be classified
as natural/intrinsic or acquired relative or absolute. Pathogens not covered by the
usual spectrum of an antibiotic are termed naturally/intrinsically resistant, e.g., 25%
of S. pneumoniae are naturally resistant to macrolides; acquired resistance refers to
a previously susceptible pathogen that is no longer susceptible to an antibiotic, e.g.,
ampicillin resistant H. influenzae. Organisms with intermediate level (relative) resistance
manifests as an increase in minimum inhibitory concentrations (MICs), but are
susceptible if achievable serum/tissue concentrations >
MIC, e.g., penicillin-resistant
S. pneumoniae. In contrast, organisms with high level (absolute) resistance manifests as
a sudden increase in MICs during therapy, and cannot be overcome by higher-than-usual
a
ntibiotic doses, e.g., gentamicin-resistant P. aeruginosa. Most acquired antibiotic resistance is
agent-specific, not a class specific, and is usually limited to one or two species. Resistance is not
related, per se, to volume or duration of use. Some antibiotics have little resistance potential
i.e., “low resistance” potential even when used in high volume; other antibiotics can induce
resistance, e.g., “high resistance” potential with little use.
The Antibiotic Resistance Potential of each antibiotic is included in each Drug
Summary (see Chapter 11).
Chapter 1. Overview of Antimicrobial Therapy
3
Table 1.1. Resistance Potential of Selected Antibiotics
Usual Organism(s)
Resistant for Each
Antibiotic
Preferred “Low
Resistance
Potential” Antibiotic
Alternatives in Same
Class
Preferred “Low
Resistance
Potential Antibiotic
Alternatives in
Different Classes
P. aeruginosa
Amikacin
Levofloxacin
or
Colistin
or
Cefepime
P. aeruginosa
Cefepime
Levofloxacin
or
Colistin
S. pneumoniae
S. aureus
Doxycycline
or
Minocycline
Levofloxacin
or
Moxifloxacin
Quinolones
Ciprofloxacin
S. pneumoniae
Levofloxacin
or
Moxifloxacin
Doxycycline
Ciprofloxicin
P. aeruginosa
Levofloxican
Amikacin
or
Colistin
or
Cefepime
MSSA
MRSA
None
Linezolid
or
Daptomycin
or
Minocycline
or
Tigecycline
P. aeruginosa
Meropenem
or
Doripenem
Amikacin
or
Cefepime
or
Colistin
“High Resistance
Potential”
Antibiotics
Aminoglycosides
Gentamicin
or
Tobramycin
Cephalosporins
Ceftazidime
Tetracyclines
Tetracycline
Glycopeptides
Vancomycin
Carbapenems
Imipenem
4
Antibiotic Essentials
Table 1.1. Resistance Potential of Selected Antibiotics (Cont’d)
“High Resistance
Potential”
Antibiotics
Usual Organism(s)
Resistant for Each
Antibiotic
Preferred “Low
Resistance
Potential” Antibiotic
Alternatives in Same
Class
Preferred “Low
Resistance
Potential Antibiotic
Alternatives in
Different Classes
S. pneumoniae
None
Doxycycline
or
Levofloxacin
or
Moxifloxacin
S. pneumoniae
None
Doxycycline
or
Levofloxacin
or
Moxifloxacin
Macrolides
Azithromycin
Dihydrofolate
Reductase
Inhibitors
TMP-SMX
Adapted from: Cunha BA. Antibiotic Resistance: Effective Control Strategies. Lancet 357:1307-1308,
2001; Cunha BA (Ed). Antibiotic Essentials (12th ed) Jones & Bartlett. Sudbury, MA 2013. p. 521-719
D. Safety Profile. Whenever possible, avoid antibiotics with serious/frequent side effects.
E. Cost. Switching early from IV to PO antibiotics is the single most important cost saving
strategy in hospitalized patients, as the institutional cost of IV administration (~$10/dose)
may exceed the cost of the antibiotic itself. Antibiotic costs can also be minimized by using
antibiotics with long half-lives, and by choosing monotherapy over combination therapy.
FACTORS IN ANTIBIOTIC DOSING
A. Renal Insufficiency. Since most antibiotics eliminated by the kidneys have a wide “toxicto-therapeutic ratio,” dosing strategies are frequently based on formula-derived esti ates of
m
creatinine clearance, rather than precise quantitation of glomerular filtration rates. Dosage
adjustments are especially important for antibiotics with narrow toxic-to-therapeutic ratios,
and for patients who are receiving other nephrotoxic medications or have preexisting renal
disease.
Chapter 1. Overview of Antimicrobial Therapy
5
1. Initial and Maintenance Dosing in Renal Insufficiency. For drugs eliminated by the
kidneys, the initial dose is unchanged, and the maintenance dose/dosing interval are
modified in proportion to the degree of renal insufficiency (CrCl). Dosing adjustment
problems in renal insufficiency can be circumvented by selecting an antibiotic with a
similar spectrum that is eliminated by the hepatic route.
2. Aminoglycoside Dosing. Single daily dosing—adjusted for the degree of renal
insufficiency after the loading dose is administered–has virtually eliminated the
nephrotoxic potential of aminoglycosides, and is recommended for all patients,
including the critically ill (a possible exception is enterococcal endocarditis, where
gentamicin dosing every 8 hours may be preferable). Aminoglycoside-induced tubular
dysfunction is best assessed by quantitative renal tubular cast counts in urine, which
more accurately reflect aminoglycoside nephrotoxicity than serum creatinine.
Table 1.2. Dosing Strategies in Hepatic/Renal Insufficiency*
Hepatic Insufficiency
• Decrease total daily dose of hepatically-eliminated antibiotic by 50% in presence of clinically severe
liver disease.
• Alternative: Use antibiotic eliminated/inactivated by the renal route in usual dose.
Renal Insufficiency (Examples)
• If creatinine clearance ~ 40–60 mL/min, decrease dose of renally-eliminated antibiotic by 50% and
maintain the usual dosing interval.
• If creatinine clearance ~10–40 mL/min, decrease dose of renally-eliminated antibiotic by 50% and
double the dosing interval.
• Alternative: Use antibiotic eliminated/inactivated by the hepatic route in usual dose.
Major Route of Elimination
Hepatobiliary
Renal
Chloramphenicol
Pyrazinamide
Most b-lactams
Amantadine
Cefoperazone
Linezolid
Rimantadine
Ceftriaxone†
Tedizolid
b-lactam/b-lactamase
inhibitors
Doxycycline
Itraconazole
Aminoglycosides
Valacyclovir
Minocycline
Isavuconazole
TMP–SMX
Famciclovir
Telithromycin
Caspofungin
Azthreonam
Valganciclovir
Moxifloxacin
Micafungin
Carbapenems
Oseltamavir
Macrolides
Anidulafungin
Polymyxin B
Zanamavir
Nafcillin
Ketoconazole
Colistin
Peramavir
Clindamycin
Voriconazole
Ciprofloxacin
Tetracycline
Metronidazole
Posaconazole
Levofloxacin
Oxacillin
Gatifloxacin
Daptomycin
Tigecycline
Acyclovir