 \212 \212 \212 The conclusion is not that urine dipstick testing is useless, but that results should not b e interpreted in isolation . Smokers and those with a +ve family history for urothelial mal ignancy may be investigated dif- ferently from those with no risk factors (e.g., US, cystos copy referral to a renal physician in some patients), but in a young fit athlete, the di agnosis is more likely to be exercise-induced hematuria. pelvic node involvement, only 6% of patients survive 5 yrs. The 3-yr survival with bilatera l or para-aortic node involvement is nil. Massive bladder hemorrhage may complicate treatme nt; consider alum solu- tion bladder irrigation (safer than formalin): It is an in-patient procedure. Gynecology Disorders of the vulva The vulva is the area surrounding the vagina that is loos ely covered by skin and is affected by pathologic processes that affect squamous epithelium . Benign disorders: Bartholin \200\231s gland cyst or abscess: Obstruction of the mucus-sec reting gland surrounding the vagina leads to superinfection; polymicrobial, needs marsupial ization and antibiotics. Undrained abscess of either Bartholin \200\231s gland or perianal glands may lead to necrotizing fas- ciitis. More common in diabetics, immuno-compromised, a nd a history of atherosclerotic disease. Premalignant and malignant conditions: Vulvar intr aepithelial neoplasia (VIN): Presents either asymptomatically or with pruritus. Appearance is white and red papular or macular rash. 5% acetic acid may help visualize. Document lesio ns and biopsy. Often associated with human papilloma virus (HPV). Look for perianal lesions as well. Histological grade : VIN I (mild dysplasia), VIN II (moderate), VIN III (severe d ysplasia or carcinoma in situ). Treatment : Local excision, CO 2 laser 515 1 JAMA 1989, Sep 1;262(9):1214 \200\2231219. Vulvar cancer: 5% of female genital malignancies; look for vaginal and ano- rectal involvem ent. VIN is usually a precursor lesion. 90% squamous cell, also melanoma. Inguinal and pelv ic lymph nodes involved in 20% of cases if lesion is <2 cm, 40% of cases if lesion is >2 cm . Treatment : Unilateral lesions <2 cm can be treated with WLE. All others are treated with WLE and bilateral inguinal/femoral lymphadenectomy. If node-negative, 5-yr survival approa ches 90%; inguinal node metastases, 40%; pelvic nodes, 20%. Disorders of the vagina Benig n disorders: Pelvic organ prolapse: Secondary to weakness in pel- vic support. Risk factors include pregnancy and childbirth, increased in intra-abdominal pressure (respiratory disea se, obesity), postmenopausal atrophy, and connective tissue disorder. Presentation: Pelvic pressure, coital difficulty, backache, protrusion from the vagina, vaginal spotting, urinar y incontinence, fecal incontinence or obstructed defecation. Evaluation: Clinical exam, uro dynamics, radiographic studies include cysto- colpoproctography, dynamic pelvic MRI. Treatm ent: Pessary if unfit for surgery. Abdominal suspension procedures including sacrocolpopexy or sacrocolpoperineopexy. Premalignant or malignant conditions: Vaginal cancer: Rare, most are extensions from either vulvar or cervical can- cers. Usually squamous cell (90%), aden ocarcinoma, sarcoma (DES expo- sure), melanoma in 10%. Surgery has a limited role. Radiatio n therapy is the mainstay. Poor survival rates. Disorders of the uterus Benign disorders: H yperplasia or uterine polyps: Presentation is abnormal uterine bleeding. Laser or cauteriza tion of the endometrium is the method of treatment. Leiomyoma (fibroids): 25% of women in r eproductive years have fibroids. Risk of malignant degeneration is <0.5%. GnRH analogs, myo mectomy, embolization, hysterectomy are all methods of treatment. Cervicitis: Common organi sms include Trichomonas vaginalis, Chlamydia trachomatis, N. gonorrhoeae, Herpes simplex vi rus. Presentation : Vaginal dis- charge, pruritus. Clinical finding s: Yellow discharge and erythematous cervix on inspection. Cervical motion tenderness on bimanual exam. Treatment is antibiotics and education. Pelvic inflammatory disease (PID): Spread of organisms in the endocervix through the endometrium to the fallopian tubes and beyond. Common organisms inc lude Chlamydia trachomatis, N. gonorrhoeae, Haemophilus influenzae. Criteria for diagnosis include lower abdominal pain, mucopu- rulent cervical discharge on exam, bilateral adnexal tenderness. Associated findings include fever, leukocytosis. Treatment : For questionable d iagnosis, laparoscopy is helpful. There are usually erythematous tubes, with a sticky exuda te. Antibiotics are the mainstay treatment. Outpatient treatment is ceftriaxone 250 mg intr amuscular and doxycycline 100 mg bid for 10 \200\22314 d. Reexamine outpatients within 48 h . A tubo-ovarian abscess is the most severe form of PID. Inpatient antibiotics will resolve abscess in 75%; drain- age is necessary either operatively or via interventional radiology in 25%. Malignant disorders Cervical cancer 20% of female genital cancers. Adenocarcinoma (90%) or squamous cell cancer (10%). Spreads primarily through direct extension and into t he regional pelvic lymph nodes. Treatment is either radiotherapy or surgery 516 with similar 5-yr survival rates. Localized disease has a 5-yr survival rate of 80 \200\223 90%; metastatic disease to the lymph nodes, 40% 5-yr survival. Endometrial cancer: Most co mmon female genital cancer. Risk factors include nulliparity, obesity, delayed menopause, c hronic anovulation, and unopposed postmenopausal estrogens. Presenting symptom is bleeding. Types include adenocarcinoma (90%). Evaluation includes transvaginal US and endometrial sa mpling. Treatment of localized disease is surgical and includes extrafascial abdominal hyst er- ectomy and bilateral salpingo-oophorectomy. Poorly differentiated endo- metrial cancer and extension into the cervix or beyond the superficial myometrium should undergo selective pelvic and periaortic lymph node sampling. Additional radiotherapy is commonly employed in these patients. 5-yr survival for superficial stage I disease is 80%; stage II disease is 60%; 30% for advanced disease. Disorders of the ovary Benign disorders: Benign follicular, corpus luteal, and theca lutein cysts are the most common. Usually disappear with new menst rual cycle or oral contraception. Cysts >10 cm are unlikely to disappear. Teratoma: Commonl y seen in women of reproductive age. Often bilateral. Ovarian cystectomy is recommended tre atment. Serous or mucinous cystadenoma: Benign epithelial tumors. Treated with cys- tectomy or oophorectomy. Intraoperative frozen section may be important to determine whether these cysts contain malignant cells. If so, and the patient is postmenopausal, bilateral oophore ctomy and hysterectomy is recommended. Ectopic pregnancy: Risk factors include history of P ID, use of infertility drugs, intrauterine contraceptive device. Any women of childbearing age with lower abdominal pain should have a \222 -HCG drawn. Small ectopic pregnancies may be treated with methotrexate. Laparoscopy or laparotomy is otherwise performed. Malignant disorders: Ovarian cancer: 25% of all female genital cancers. Risk factors include \206 \221 age, \206\223 fertility, family history, Peutz \200\223Jeghers \200\231 syndrome, Tur ner \200\231s syndrome. Presentation is often late and consists of abdominal pain and swell ing, GI symptoms, adnexal mass. Evaluation: CBC, chemistry, CA-125, -fetoprotein, CT, IV P. Treatment: Abdominal hysterectomy with bilaterally salpingo-oophorectomy, lymphadenectom y, and tumor cytoreduction. Adjuvant chemotherapy (Taxol) and/or radiation are given for ad vanced disease. 5-yr survival from epithelial ovarian cancer is 70% for stage I, 30% for st age II, and <15% for stage III and IV. y r e g r u S 517 Infectious diseases (ID ) Shmuel Shoham , M.D. s e s a e s i d Contents U.S. notifiable diseases 519 Pathogens 520 Travel advice 524 Overview of antimicrobial susc eptibility 526 Antibiotics 529 Penicillins 529 Cephalosporins 530 Aminoglycosides 532 Macro lides 533 Quinolones 533 Carbapenems 534 Empiric treatment 536 Adult Immunization 539 Drug abuse and infectious diseases 540 Fever of unknown origin 542 Gastroenteritis 543 Evaluatin g the tropical traveler 546 Malaria 549 Mycobacterium tuberculosis 552 Tuberculosis diagnos is and treatment 554 Herpes infections 557 Infectious mononucleosis 559 Cytomegalovirus 560 Nonspecific upper respiratory tract infections (common cold) 561 Influenza 562 Poliomyelit is 563 Toxoplasmosis 563 Viral hepatitis 564 Human immunodeficiency virus/AIDS 566 Sexually transmitted infections 574 Vaginal discharge and urethritis 577 Infections associated with animal contact 578 Miscellaneous gram-positive bacteria 579 Miscellaneous gram-negative ba cteria 582 s u o i t c e f n I 4 1 518 Tetanus 584 Enteric fever 585 Bacillary dysentery 585 Cholera 585 Hansen \200\231s disease (leprosy) 586 Spirochetes 587 Viral hemorrhagic fevers 588 Rickettsia and arthropod-borne b acteria 589 Giardiasis 591 Amebiasis 591 Trypanosomiasis 592 Leishmaniasis 593 Fungal infec tions 594 Nematodes (roundworms) 598 Filarial infections 599 Cestodes (tapeworms) 600 Trematodes (flu kes) 601 Exotic infections 602 s e s a e s i d s u o i t c e f n I U.S. notifiable diseases Table 14.1 Notifiable infectious diseases in the U.S. (adults) Arthropod-borne viral infections: California serogroup virus, Dengue Eastern equine encepha litis, Powassan virus, St. Louis encephalitis, West Nile virus Diarrheal/enteric infections : Cholera, cryptosporidiosis, cyclosporiasis, giardiasis, hemolytic ure- mic syndrome (post -diarrheal), salmonellosis, Shiga toxin-producing Escherichia coli (STEC), shigellosis Diss eminated diseases of food/water/livestock origin: Brucellosis, listeriosis, trichinellosis (trichinosis), typhoid fever, vibriosis HIV infection Infections preventable by routine vac cination: Diphtheria, measles, mumps, pertussis, rubella, varicella (morbidity and death) R espiratory tract-predominant infections: Coccidioidomycosis, Haemophilus influenzae (invasi ve disease), han- tavirus pulmonary syndrome, legionellosis, novel influenza A virus infect ions, psittacosis, Q fever, severe acute respiratory syndrome-as- sociated coronavirus (SAR S-COV), Streptococcus pneumoniae (invasive disease),tuberculosis Parasitic infections: Babe siosis, malaria Potential agents of bioterrorism/biowarfare: Anthrax, botulism, plague, sma llpox, tetanus, viral hemorrhagic fevers (Ebola, Marburg, Crimean-Congo hemorrhagic fever, Guanarito, Junin, Lassa, Lujo, Machupo, Sabia, and yellow viruses) Sexually transmitted inf ections: Chancroid, Chlamydia trachomatis infection, gonorrhea, syphilis Tick-borne bacteri al infections: Anaplasma phagocytophilum , Ehrlichia chaffeensis , Ehrlichia ewingii , lyme disease, spotted fever, rickettsiosis, tularemia Viral hepatitis infections: Hepatitis A, B, C Other: Hansen \200\231s disease (leprosy), meningococcal disease, rabies, toxic-shock syndrome, vancomycin-intermediate or -resistant Staphylococcus aureus (VISA, VRSA) 519 Note: Classifications in blue are for guidance only. There is extensive overlap between gro ups National Notifiable Infectious conditions (United States Department of HHS, CDC) Pathogens Table 14.2 Examples of bacterial pathogens from different classes \222 -hemolytic streptococci: S. pyogenes (Group A) , S. dysgalactiae (Group C, G) \222 - or -hemolytic: S. agalactiae (Group B) \222 - or -Hemolytic: S. bovis spp. (Group D ), S. salivarius spp. \222 -, \222 -, or -hemolytic: S. anginosus spp. (Group A, C, F, G) , S. mutans spp. Enterococci ( -hemolysis): E. faecalis, E. faecium Gram-negative ba cilli (cont.) Enterobacter species, Escherichia coli (multiple pathotypes) Francisella tula rensis Haemophilus influenza, H. parainfluenza, H. ducreyi Hafnia alvei Helicobacter pylori Klebsiella species Morganella morganii Pantoea agglomerans Pasteurella multocida Plesiomon as shigelloides Proteus species Providencia species Pseudomonas aeruginosa Salmonella enter ica (many serotypes) Serratia marcescens Shigella spp. Stenotrophomonas maltophilia Vibrio cholerae, V. parahaemolyti- cus, V. vulnificus Yersinia species Anaerobes: Bacteroides spec ies, Fusobacterium species, Prevotella species, Porphyromonas spp. Mycobacteria M. tubercul osis M. leprae M. bovis M. abscessus, M. avium com- plex, M. chelonae, M. fortuitum, M. mar inum, M. kansasii Gram-positive cocci Coagulase-positive staphylococci: S. aureus Coagulase-negative or inter mediate: S. lugdunensis Coagulase-negative: S. epidermidis Streptococcia: \222 -Hemolytic streptococci: S. pneumoniae, S. mitis spp. Other streptococci: Nutritionally variant strept ococci: Abiotrophia defectiva, Granulicatella sp., Anaerobic streptococci Gram-positive bac illi Aerobes: Bacillus anthracis , B. cereus Corynebacterium diphtheriae Listeria monocytog enes Nocardia species Other coryneforms (diphtheroids) Anaerobes: Clostridium botulinum, C. difficile , C. perfringens , C. tetani Actinomyces israelii, A. Naeslundii, A. odontolytic us, A. viscosus Gram-negative cocci Neisseria meningitidis, N. gonorrhoeae Moraxella catarr halis Gram-negative bacilli Acinetobacter baumannii complex Bordetella pertussis Brucella s pecies Burkholderia cepacia Campylobacter species Citrobacter species Edwardsiella tarda Ob ligate intracellular bacteria Anaplasma phagocytophilum Bartonella bacilliformis, B. hensel ae, B. quintana Chlamydia trachomatis, C. psittaci, C. pneumoniae Coxiella burnetii Ehrlich ia chaffeensis, E. ewingii Legionella pneumophila Mycoplasma pneumoniae Rickettsia ricketts ii (RMSF), R. prowazekii 520 (Continued) s e s a e s i d Table 14.2 (Continued) Spirochetes Treponema pallidum (syphilis) Leptospira (leptospirosis) (Lyme), burgdorferi Bo rrelia Borrelia species , other (relaps- ing fever) species s u o i t c e f n I a Streptococci are classified according to hemolytic pattern ( \222 , green; \222 , clear ; , nonhemolytic), by Lancefield antigen group (A \200\223G), or by species (e.g., S. py ogenes ). Table 14.3 Viruses Herpes viruses (double-stranded DNA) Normal host Orolabial > genital, Immunocompromised More severe and Herpes simplex meningoencephalitis, keratitis recurrent mucocuta- neous disease More severe and virus 1 (HSV \200\2231 ) Herpes simplex Genital > orolabial more, recurrent aseptic meningitis, keratitis recurrent mucocuta- neous disease virus 2 (HSV \200\2232) Varicella zoster virus (VZV) Varicella, zoster (reactivation) More severe and recur- rent disease, Central nervous system (CNS), retinal disease Cytomegalovirus Mononucleosis syndrome Nonspecific viral syn- (CMV ) drome, GI, liver, CNS, retina, lung, bone marrow manifestations Epstein \200\223Barr virus (EBV) Mononucleosis syn- Lymphoma, post- drome, lymphoma, nasopharyngeal carcinoma transplant lymphopro- liferative disease Human herpes virus 6 and 7 (HHV \200\2236, HHV \200\2237) Infants: Fever followed by rash, may have CNS involvement with seizures (known as roseola i nfantum, sixth disease) Similar to CMV infection 521 Human herpes Asymptomatic carriage Kaposi \200\231s sarcoma virus 8 (HHV \200\2238) Polyoma viruses (double-stranded DNA) Normal host Asymptomatic carriage Immunocompromised Hemorrhagic cystitis, BK virus nephropathy JC virus Asymptomatic carriage Progressive multifocal leukoencephalopathy (PML) (Continued) Table 14.3 (Continued) Pox viruses (double-stranded DNA) Variola Vaccinia Molluscum Smallpox (eradicated) Used for vaccination to protect against smallpox Pearly skin papules contagiosum Hepatitis viruses Hepatitis A (RNA) Acute, sometimes fulminant infection Hepati tis B (DS Self-resolving or chronic infection DNA) Hepatitis C (RNA) Hepatitis D (RNA) Accelerates hepatitis B Hepatitis E (RNA) Acute, someti mes fulminant infection Self-resolving, or more commonly chronic infection Single-stranded DNA virus Fever with slapped-cheek appearance in kids Parvovirus B19 (erythema infectiosum; fifth disease), arthritis in adults, red blood cell aplasia in immun ocompro- mised and patients with RBC disease Retroviruses HIV \200\2231 HIV \200\2232 Major cause of HIV disease/AIDS worldwide Uncommon cause of HIV disease/AIDS, predomi- nant ly found in West Africa, immunodeficiency develops more slowly and is milder compared with HIV \200\2231 HTLV \200\2231 Mostly asymptomatic, 5% develop adult T-cell leukemia (ATL) 1% myelopathy/tropical spastic paraparesis (HAM/TSP) HTLV \200\2232 Associated with intravenous drug use (IVDU), not clearly associated with disease Orthomyxoviruses (SS RNA) Major causes of respiratory viral infections Influenza virus A, B, C Paramyxovirus (SS RNA) Major causes of respiratory viral infections Can cause severe diseas e in bone marrow trans- Parainfluenza RSV plant recipients 522 Other viruses frequently associated with respiratory tract infection Major cause of common cold Respiratory tract infections Respiratory, GI, bladder, conjunctivae or skin Rhinoviruses Metapneumovirus Adenovirus (>50 serotypes) Enteroviruses manifestations Coxsackie A, B, echovirus (meningitis, gastroenteri- tis, pericarditis, pleuritis, rash) Coronaviruses Respiratory and GI infections (Continued) s e s a e s i d Table 14.3 (Continued) Mosquito-borne viruses Dengue Endemic in urban areas of many developing coun- tries, fever, headache, myalgias, bone pain s u o i t c e f n I Yellow fever Encephalitis viruses Eastern equine, St. Louis, Western equine, West Parts of Africa, South America; vaccine preventable Nile, Japanese encephalitis (vaccine preventable) Viruses frequently associated with GI illness Noroviruses Major cause of gastroenteritis; cruise ships, cafeterias Rotavirus Major cause of diarrhea Viruses preventable by routine vaccinations Measles Mumps Rubella Outbreaks in unimmunized populations Causes fevers, myalgias, parotitis Intrauterine diseas e associated with major congeni- tal abnormalities Polio Outbreaks continue in Asia, Africa Viruses transmitted by animal exposure Rabies Herpes B Monkeypox Orf Hantavirus Ebola, Marburg Rift valley, Congo- Crimean HF, Alk hurma viruses Lassa virus Avian influenza Lymphocytic cho- riomeningitis virus (LCM) Bats, raccoons, foxes, dogs and cats; encephalitis Monkeys, severe CNS infection Exotic pet s, fever, rash Goat and sheep, skin infection Rodents, severe pulmonary disease Bats, bushm eat, hemorrhagic virus, high mortality Livestock slaughter and consumption of raw milk Rodents, West Africa, fevers, bleeding Domestic poultry, high mortality Rodents, CNS infect ion 523 Fungal pathogens Yeasts: Candida albicans Other Candida spp. (e.g., C. glabrata, C. parapsi losis, C. krusei, C. tropicalis ) Cryptococcus neoformans, C. gattii Filamentous fungi: Asp ergillus fumigatus Other Aspergillus spp. (e.g., A. flavus, A. niger, A. terreus ) Fusarium spp. Zygomycetes (mucormycosis) Dark molds (e.g., Bipolaris spp ., Alternaria spp ., Ochro conis spp.) Endemic mycoses: Histoplasma capsulatum Blastomyces dermatitidis Coccidioides i mmitis Dermatophytes: Trichophyton rubrum, T. tonsurans Microsporum canis Travel advice The majority of travel-related illnesses are not infections but due to other events such as motor vehicle accidents or flare of an underlying illness. Many infections can be avoided with adherence to prevention methods. Advice to travelers is more important than vaccinatio n . This is extremely important in foreign-born travelers who are returning to their countr y of origin after living in the United States for many yrs. An understanding of the travele r \200\231s health history, itinerary, and expected activities abroad is essential to provi ding good advice. Topics to cover include general safety and hygiene, illegal drug use, foo d and water safety, prevention of arthropod bites, animal avoidance, safer sex practices, a nd malaria pro- phylaxis and counterfeit drugs. Travelers \200\231 diarrhea, typhoid, malar ia, and dengue are major concerns . Traveler \200\231s diarrhea (affects 30 \200\22370% of travelers) : Common causes: Noroviru ses, rotavirus, enteroviruses, E. coli, Campylobacter jejuni, Salmonella, Shigella, and Vib rio . Prevention: Hand hygiene : Cleanse hands with soap and water or alcohol gel before ha ndling food and after contact with animals, infants, or toilet facilities. Water/beverages safety : Avoid ingesting tap water (including during brushing teeth) unless sure it is not contaminated. If in doubt, water should be boiled, disinfected, or filtered. In many develo p- ing countries, assume that all nonbottled water is unsafe. With bottled water, ensure th e rim is clean and dry. Avoid ice, including popsicles or flavored ice that may have been m ade with contaminated water. Boiled beverages that are still hot (e.g., tea and coffee), co mmercially prepared beverages in sealed containers, and pasteurized drinks are generally sa fe. Food safety: Fully cooked food that is still hot is safest. Avoid food and beverages ob tained from street vendors, buffets, salads, and raw fruits and vegetables that cannot be p eeled. Travelers should peel their own fruit. If you cannot wash your hands, discard the pa rt of the food that you are holding. Meals cooked in homes of friends and relatives are usu ally safer than restaurant food. Vaccination: Typhoid (see travel vaccine table). 524 s e s a e s i d Treatment: Consider advising higher risk travelers to have antimicro- bial therapy on hand (ciprofloxacin, levofloxacin, or azithromycin for 1 \200\2233 d). Antimotility drugs (e.g., loperamide or diphenoxylate) can be used for symptom relief until the antibiotics take eff ect. Fluid and elec- trolyte replacement is an important adjunct, especially in children an d in those with chronic medical conditions. Mosquito-, tick-, and other arthropod-borne inf ections: Malaria, dengue, yellow fever, Japanese encephalitis, chikungunya, tick borne infe ctions Prevention: Avoid areas in the midst of outbreaks, use protective clothing and shoes , check for ticks, and use bed nets as appropri- ate, use repellents (DEET, picaridin, oil of lemon, eucalyptus, IR3535). Vaccinations: Yellow fever, Japanese encephalitis (see trave l vaccine table) s u o i t c e f n I Malaria chemoprophylaxis Medication Start time before entry to malarious area 1 \200\2232 d Stop time after leav- ing area Usage areas Atovaquone 250 mg/ Proguanil 100 mg/d Chloroquine 500 mg (salt)/wk 7 d All 7 \200\22314 d 28 d Chloroquine sensitive areas only All Chloroquine sensitive areas only All except parts of S E Asia Doxycycline 100 mg/d 1 \200\2232 d 7 \200\22314 d Hydroxychloroquine 400 mg (salt)/wk 28 d 28 d Mefloquine 250 mg (salt)/wk If area has poor medical care and traveler is not pregnant, con sider carrying reliable supply regimen of atovaquone/proguanil or artemether/ lumefantrine for presumptive self-treatment. Medical care should be sought as soon as possible. Vaccines for adult travelers First make sure patients are up-to-date on their routine immunizations . Vaccine needs differ by details of travel and traveler \200\231s health status. Vaccine Y ellow fever ( LIVE VIRUS) Typhoid 14 d 28 d Schedule 1 dose SQ 10 yrs 2 yrs Vi capsular: IM \227 1 5 yrs (repeat series) Ty21a (LIVE): PO every other day \227 4 1 dose IM booster 525 Tetanus (previously vaccinated) 10 yrs Inactivated Polio (previously vaccinated) 1 dose SQ 10 yrs Rabies pre-exposure 3 doses IM: d 0,7,21 \200\22328 Meningococcal quadrivalent MCV4: 1 dose IM MPSV4:1 dose SQ 2 doses IM: d 0 and 28 2 doses IM HAVRIX: D 0 and 6 \200 \22312 months VAQTA: Day 0 and 6 \200\22318 months 3 doses IM: Day 0, 1 month, 4 \200\2236 months 3 \200\2235 yrs Japanese encephalitis JE-VC 1 year Hepatitis A Hepatitis B Suggested vaccines: Africa: Meningitis, typhoid, diphtheria, tetanus, polio, hepatitis A yellow fever (many countries insist on it for entry). Asia: Meningitis (quadrivalent vacci ne against meningitis A, C, W135, and Y for Saudi Arabia), typhoid, diphtheria, tetanus, po lio, hepatitis A; con- sider rabies and encephalitis. S. America: Typhoid, diphtheria, teta nus, polio, hepatitis A yellow fever. Travel if immunocompromised: Avoid live vaccines. Hepatitis B vaccine. CDC 2012 Yellow Book Overview of antimicrobial susceptibility 526 Table 14.5 Susceptibility of some bacteria to certain antibiotics s e n e g o t y c o n o m . Agents p p s . . c b o r e a n a g e N e s a l u g a o C 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 p e r t S c b o r e a n a e a n o m u e n p i s a n o m o d u e s P . i p p s e a z n e u l f n r e t c a b o r e t n E 0 0 0 0 1 0 0 1 1 1 2 2 2 1 2 . i p p s a s o n g u r e a s n a d i r i V s i l a . l s l a c p y t a o m e h - B 2 2 2 1 1 2 2 2 2 0 2 1 0 2 0 l l a c e a f a i t a r r e S e i s b e K 0 0 1 0 2 2 2 2 2 2 2 2 2 2 2 A S R M 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 . i A S S M 0 0 2 2 2 2 1 1 1 0 1 1 0 1 0 i l h p a t S i l a r O 2 1 2 0 2 0 2 1 1 0 2 2 0 2 0 o c a r o a r o t u G 0 0 2 0 2 0 1 0 0 0 2 2 0 1 0 i e r v . l . . H 0 1 2 0 2 2 2 2 2 2 2 2 2 2 2 . . . E 2 2 2 0 2 0 0 0 0 0 0 1 0 0 0 E 0 1 1 0 2 1 2 2 2 2 2 2 1 1 2 l f l f S S L PCN -G Ampicillin Ampicillin/sul Oxacillin Piperacillin/taz Cefazolin Cefotetan Ceftriaxone Cefepime Aztreonam Ertapenem Meropenem Ciprofloxacin Moxifloxacin Gentamicin 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 1 1 1 2 1 2 2 0 2 1 0 2 0 2 2 2 1 1 2 1 2 2 0 2 1 0 2 0 1 2 2 0 0 0 0 0 0 0 0 1 1 0 0 0 0 0 0 2 0 0 2 2 2 2 2 2 2 2 0 0 0 0 2 0 0 0 2 1 0 2 1 0 2 0 0 0 0 0 0 0 0 0 0 0 0 2 2 0 (Continued) 5 2 7 Infectious diseases 5 2 8 Table 14.5 (Continued) s e n e g o t y c o n o m . Agents p p s . . c b o r e a n a g e N e s a l u g a o C 0 0 1 2 2 2 0 1 0 p e r t S c b o r e a n a e a n o m u e n p i s a n o m o d u e s P . i p p s e a z n e u l f n r e t c a b o r e t n E 2 0 0 0 0 0 2 1 0 . i p p s a s o n g u r e a s n a d i r i V s i l a . l s l a c p y t a o m e h - B 0 1 2 1 2 2 0 1 0 l l a c e a f a i t a r r e S e i s b e K 2 0 0 0 0 0 2 1 0 A S R M 0 0 1 2 2 2 2 1 0 . i A S S M 0 0 1 2 2 2 2 1 0 i l h p a t S i l a r O 0 1 2 0 0 0 0 1 1 o c a r o a r o t u G 0 0 1 0 0 0 0 1 2 i e r v . l . . H 0 2 0 0 0 0 1 1 0 . . . E 0 0 0 2 2 2 0 1 0 E 2 0 0 0 0 0 1 1 0 l f l f S S L Colistin Azithromycin Clindamycin Vancomycin Daptomycin Linezolid TMP/SMX Doxy. Metro. 0 0 0 0 2 2 0 1 0 0 1 1 2 2 2 0 1 0 0 1 1 2 2 2 0 1 0 0 0 0 0 0 1 2 0 0 0 0 0 0 0 0 1 0 0 2 0 0 0 0 0 0 0 0 0 2 1 0 0 0 0 2 0 0: High rates of resistance 1: Some decreased susceptibility 2: High levels of susceptibili ty Bold numbers indicate drug of choice for initial therapy Antibiotics General advice: If possible, know what organism is causing the infection. Balan ce the need for early antimicrobial therapy with the danger of inap- propriate antibiotic u se. Consider: What is the margin of error for delaying effective therapy in this patient? W hat data (history, physical, laboratory tests, radiographs, knowledge of local microbial su sceptibility profiles) are needed to determine if the infection is amenable to antibiotic t herapy and with which drug? Make every effort to obtain cultures of blood, urine, spu- tum, and any other relevant samples before treating with empiric antibiotics. Consider whether an antibiotic needs to be started or whether you can wait for laboratory results. Ask: Is s urgery or device removal needed? Is the antibiotic safe for this patient (drug interaction, allergies, toxicity profile)? Will the antibiotic penetrate the site of infection? Once th erapy is started, consider: Can the spectrum of coverage be narrowed? Is an antibiotic stil l required? Is the treatment course long enough? Is a less expensive, but equally safe and effective option available? In unstable and immunocom- promised patients, earlier therapy w ith broader coverage can save lives. However, inappropriate use of antimicrobials in the ge neral patient popu- lation and failure to control a source of infection can lead to worse o ut- comes, promote antibiotic resistance, and increase costs. s e s a e s i d s u o i t c e f n I Penicillins Table 14.6 Antibiotic (and its uses) Usual adult dose Adjustment for creatinine clearance (mL/min) PCN-G: Creatinine clearance (CrCl) 10 \200\223 50:1 \200\2233 MU/4 h,<10:1 \200\2232 MU/4 \200\2236 h Penicillin (PCN): Aqueous PCN Most streptococci, Meningococcus, Gonococcus , syphilis, gas gangrene, anthrax, actino- myc osis, and many anaerobes G: 2 \200\2234 million U (MU)/4 h IV PCN/Benzathine (Bicillin L-A) 2.4 million U IM PCN VK 250 \200\223500 mg/6 h PO 1 \200\2232 g/4 \200\2236 h IM/IV HD : 2 MU/4 \200\2236 h (give dose after HD or + 0.5 MU after HD) Ampicillin: Broader spectrum than penicillin; more active against gram- negative rods, but \222 -lactamase sensi- tive. Amoxicillin is better absorbed PO. CrCl 10 \200\22350: q6 \200\2238h, <10: q8 \200\22312h HD: q8 \200\22312h (give dose after HD) 529 Amoxicillin: As 250 \200\223500 mg/8 h PO; can use 875 mg/12 h in urinary tract infection (UTI) or streptoc oc- cal cellulitis, 1,000 mg/8 h in penicillin (PCN) intermedi- ate pneumococcal pneumonia CrCl 10 \200\22330: 250 \200\223500 mg/12 h, <10: 500 mg/d ampicillin but better absorbed PO. For IV therapy, use ampicillin. HD: 500 mg/d (give dose after HD) (Continued) Table 14.6 (Continued) Antibiotic (and its uses) Usual adult dose Adjustment for creatinine clearance (mL/min) Amoxicillin/clavu- 250 \200\2231,000 mg/8 h PO CrCl 10 \200\22330:250 \200\223500 lanate : \222 - lactamase inhibitor confers a much broader spectrum than amoxicillin alone . Ampicillin/sulbac- tam: Abdominal sepsis, diabetic foot infections, severe respira- tory infections, head and neck infections Dicloxacillin: For mg/12 h, <10 and HD: 250 \200\223500 mg/24 h 1.5 \200\2233 g/6 h IV CrCl 15 \200\22330: q12h, CC <15: q24h HD: 1.5 g q12h + 2 g after HD 125 \200\223500 mg/6 h No adjustment MSSA skin, soft-tis- sue, and respiratory tract infections 1 \200\2232 g/4 \200\2236 h. Higher doses with bacteremia No change Oxacillin, nafcillin: serious MSSA For infection Penicillin side effects The most common are hypersensitivity reactions (ranging from rash t o anaphylaxis) and GI upset. With detailed questioning, many patients who report PCN hypers ensitivity turn out to have had nonallergic reactions. Rashes with ampicillin do not necess arily indicate penicillin allergy, but a patient who is truly penicillin allergic likely ha s allergy to all penicillins. Large doses or intrathecal injections can cause seizures and coma. Less common side effects are C. difficile colitis, electrolyte imbalance with IV ther apy, and interstitial nephropathy. Cephalosporins Spectrum Most cephalosporins are active against methicillin-sensitive staphy lococci (including \222 -lactamase producers), streptococci (except group D, Enterococcus faecalis and faecium ), pneumococci, E. coli , some Proteus, Klebsiella, Haemophilus, Salmo nella , and Shigella . Second- generation drugs (cefuroxime, cefamandole) are active agains t Neisseria and Haemophilus . Third-generation drugs (cefotaxime, ceftazidime, ceftri- axon e) have better activity against gram-negative organisms. Ceftazidime has less gram-positive activity, especially against S. aureus, and is used in the treatment of Pseudomonas infect ions. Cefepime is fourth-generation and has activity against both gram-positive and gram-ne gative aerobic bacteria (including Pseudomonas) . Ceftaroline has activity against methicil lin-resis- tant Streptococcus aureus MRSA, but not Pseudomonas . Cephalosporins (cefaclor, cefadroxil, cephradine, cephalexin, Uses cefuroxime axetil) may be used in pneumonia, otiti s media, skin and soft tissue infections, and UTIs. The oral cephalosporins are generally s econd-line agents or used to complete an antibiotic course started 530 with an IV cephalosporin. The major use of cephalosporins is parenteral; e.g., as prophylax is in surgery and in postoperative infection. Suspected life-threatening infections (e.g., severe pneumonia, meningitis, or gram- negative septicemia) may be treated empirically with a third-generation drug. Cephalosporins may also become the drugs of first choice in certa in situations, such as penicillin hypersensitivity (beware of 10% cross- sensitivity) or w here aminoglycosides are better avoided. The main adverse effect of the cephalosporins is h ypersensitivity. This is seen in <10% of penicillin-sensitive patients. There may be GI ups et, reversible changes in liver function tests, eosinophilia, rarely neutropenia, nephrotox icity, and colitis. There are reports of clotting abnormalities, and there may be false-pos itive results for glycosuria or the Coombs \200\231 test. Most broad-spectrum cephalosporin s potentiate warfarin. There are over a dozen cephalosporins on the market. A representativ e sample is presented below: s e s a e s i d s u o i t c e f n I Table 14.7 Cephalosporins Antibiotic (and its uses) Usual adult dose Adjustment for creatinine clearance (mL/min) First-generation cephalosporins Cefazolin: Range of 1 \200\2232 g/6 \200\2238 h IV. Use higher doses with bacteremia 250 \200\223500 mg/6 CrCl 10 \200\22335: 0.5 \200\2231 g/12 h, infections due to MSSA, susceptible streptococci, E. coli and other gram-negative aerobes <10: 0.5 \200\2231 g/24 h HD:0.5 \200\2231 g/24 h + 1 g after HD Cephalexin: Similar in CrCl 10 \200\22330: q8 \200\22312h, <10: spectrum to cefazolin, but in oral formulation h PO q12 \200\22324h HD: Q12 \200\22324h dose after HD Second-generation cephalosporins 0.75 \200\2231.5 g Cefuroxime: Range of infec- tions due to susceptible streptococci and gram- negative aerobe s, esp. respiratory and GU CrCl 10 \200\22350(IV): Q8 \200\22312h, <10 (IV) 0.75 g/24, (PO) 250 mg/24 h HD: Give dose after HD /6 \200\2238 h IV 250 \200\223500 mg/12 h PO 0.5 \200\2233 g/12 h IV Cefotetan: Range of infec- tions due to susceptible gram-negative aerobes, and anaerobes, e sp. GI/GU CrCl 10 \200\22330 1 \200\2232 g/24, <10 1 g/24 \200\22348 h HD: 0.5 \200\2231 g/24 h + 1 g after HD 531 Third-generation cephalosporins Ceftriaxone: Many gram- positive and negative infections. Excellent CNS levels. Not active against Listeria, enterococci, and Pseudomonas 1 \200\2232 g/12 \200\22324 No adjustment h IV Cefixime: Similar in spec- trum to ceftriaxone 400 mg/24 h CrCl 10 \200\22350: 300 mg/d, PO <10: 200 mg/d HD: 300 mg/d, give dose after HD (Continued) Table 14.7 (Continued) Antibiotic (and its uses) Usual adult dose Adjustment for creatinine clearance (mL/min) Advanced-generation cephalosporins Cefepime: Good activ- 1 \200\2232 g/8 h IV CrCl 30 \200\22360: 1 \200\2232 g/12 \200\22324 h, <30:0.5 \200\2232 g/24 h HD: 0.5 \200 \2232 g/24 + 1 g ity against Pseudomonas , Enterobacter , and other resistant gram-negative organisms, and S . aureus . Ceftaroline: Many gram- positive and -negative infec- tions and MRSA; not active against Pseudomonas after HD or dose after HD 600 mg/12 h IV CrCl 30 \200\22350: 400 mg/12 h, 15 \200\22330:300 \200\223400 mg/12 h, <10: 200 \200\22340 0 mg/12 h Aminoglycosides These are broadly active against aerobic gram-negatives and synergistic wit h ampicillin in enterococcal endocarditis. Monitor levels and avoid extended therapy to red uce chance of renal and inner ear toxicities. AGs are dosed once daily or intermittently. O nce daily is not recommended for meningitis and patients with renal dysfunction. In the lat ter, use intermittent dosing, start with standard loading dose, obtain pharmacist assistanc e for further dosing, follow levels closely, and consider nonaminoglycosides options. Try t o avoid use in patients with myasthenia gravis, concomitant nephrotoxic drugs, and pregnanc y. Table 14.8 Aminoglycosides Gentamicin Once daily: 5 \200\2237 mg/kg/24 h. Target trough <1 (mcg/mL) Intermittent: 2 \200\2233 mg/ kg load then 1.7 \200\2232 mg/ kg/8 h. Target Peak >6 \200\2238, trough <2 (mcg/mL) Enteroc occus synergy: 1 mg/kg/8 h, target peak 3 \200\2235 (mcg/mL) Once-daily dosing : 15 \200 \22320 mg/kg/24 h. Target trough <4 (mcg/mL) Intermittent dosing : 8 \200\22312 mg/kg load then 7 \200\2238 mg/kg/8 h or 7.5 \200\22310 mg/kg/12 h. Target peak >20 \200\22335, trough <10 (mcg/mL) Amikacin: resistance organisms gentamicin L ess in some to than 532 Macrolides Active against many community respiratory tract pathogens, travelers \200\231 di arrhea, H. pylori , sexually transmitted infections, nontuberculous mycobacteria. s e s a e s i d s u o i t c e f n I Table 14.9 Macrolides Sinusitis/pharyngitis/otitis media/bronchitis/ pertussis/mild community acquired pneu- moni a (CAP): 500 mg day 1 then 250 mg/d \227 4 d Mild to moderate CAP: 500 mg/d \227 5 \200 \22310 d Moderate to severe CAP: Add \222 -lactam Non-gonococcal urethritis/cervicitis/ C. tra- chomatis infection: 1 g \227 1 dose Non-TB mycobacterium (e.g., M. avium intracellul are [MAI] ): 500 mg/24 h as part of combination therapy MAI prophylaxis: 1,200 mg/wk Travel ers \200\231 diarrhea: 500 mg/24 h for 1 \200\2233 d Sinusitis/pharyngitis/otitis media/bro nchitis: 250 \200\223500 mg/12 h \227 7 d Pertussis: 500 mg/12 h \227 7 d Mild-moderate C AP: 250 \200\223500 mg/12 h \227 7 \200\22314 d Non-TB mycobacterium (e.g., MAI): 500 mg/1 2 h as part of combination therapy H. pylori ulcer: 500 mg/12 h as part of com- bination th erapy \227 10 \200\22314 d Azithromycin: Available as IV or oral therapy, gen- erally well tolerated . No change for d ecreased filtration glomerular rate (GFR) Clarithromycin: More GI upset than azithromy- cin, multiple drug interac- tions, mostly via P-450 metabolism. Decrease to q24h for CrCl <50 Quinolones Active against many community-acquired respiratory, GU, and GI pathogens. Member s of this class are available in oral and IV formulations and are the only oral option for susceptible Pseudomonas aeruginosa . Table 14.10 Quinolones 250 \200\223750 mg/12 h PO 200 \200\223400 mg/12 h IV Higher doses and longer courses for m ore compli- cated and severe infections Ciprofloxacin: Used in adult cystic fibrosis, typhoid, Salmonella , Campylobacter , prostat itis, and serious or resistant infections. Avoid overuse. CrCl <30:400 mg/24 h IV, PO: 250 \200\223500 mg/12 h PO, HD: 200 \200\223400 mg/ 24 h IV, 2 50 \200\223500 mg/24 h HD: Give dose after HD CrCl <50: 250 533 Levofloxacin: Less active against Pseudomonas Moxifloxacin: Less active against Pseudomonas , poor urine penetration 250 \200\223750 mg/24 h IV or PO mg/24 \200\22348 h IV 400 mg/24 h IV or PO No adjustment Carbapenems Very broad-spectrum activity against gram-positive, gram-negative, and anaerobi c bacteria. Stenotrophomonas, MRSA, and carbapenemase produc- ing gram-negative rods not su sceptible. Imipenem has better activity against E. faecalis than ertapenem and meropenem. C arbapenems may cause sei- zures, particularly imipenem. Table 14.11 Carbapenems 1 g/24 h IV Ertapenem: Not active against P. Aeruginosa and Acinetobacter. Imipenem/Cilastatin: Most li kely to cause seizures. CrCl <10: 500 mg/24 h HD: 500 mg/24 h and dose post HD 500 \200\2231,000 mg/6 \200\2238 h IV CrCl 40 \200\22370:500 mg/6 \200\2238 h IV,20 \200\22340: 250 mg/6 h or 500 mg/8 h, <20 250 \200\223500 mg/12 h HD: 250 mg/12 h + 250 mg after HD Consider meropenem with lower CrCl 1 \200\2232 g/8 h IV Meropenem: May be used in CNS infections