6 SURGERY II 3 - Urologic Infections

Surgery II 6.3

Dr. Jose Benito Abraham February 16, 2015

GENITO-URINARY INFECTIONS OUTLINE I. Urinary Tract Infection a. Epidemiology b. Pathogenesis c. Diagnostic Principle d. Imaging Studies e. Prophylactic Antimicrobial Therapy f. Classification of UTI g. Categories of UTI h. Specific UTI II. Vesicourethral Reflux III. Specific Complicated Genitourinary Infectious State IV. Key Points REFERENCES 1. Lecture PPT 2. 2015B trans 3. 2015A trans 4. Schwartz 5. Sabiston 6. Centers for Disease Control and Prevention: http://www.cdc.gov/std/treatment/2010/urethritis-and-cervicitis.htm Lecture recording 7. Unicorn 2015

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URINARY TRACT INFECTION Inflammatory response of the urothelium to bacterial invasion Associated with bacteriuria and pyuria Bacteriuria o Presence of bacteria in the urine o May represent specimen contamination  Presence of bacteria is not synonymous with UTI. If only bacteria, then it is due to contamination, poor handling technique, or catheter contamination. o Symptomatic or asymptomatic (screening bacteriuria) Pyuria o Prerequisite for the diagnosis of UTI o Inflammation of the urothelium o Pyuria with bacteriuria – confirms INFECTION o Bacteriuria without pyuria indicates colonization without infection o Pyuria without bacteriuria indicative of tuberculosis, stones or cancer 1,3 o if negative culture – sterile pyuria, think of other diseases EPIDEMIOLOGY UTIs are the most common bacterial infection Account for 7 million visits to the physician’s office 1 million visits to the emergency room 100,000 hospitalization annually They account for 1.2% of all office visits by women and 0.6% of all office visits by men Infection in females increases at the onset of sexual intercourse. o Starts to rise around 18 years of age. o Staph saphrolyticus causes symptomatic UTI to young sexually 7 active female (10%) Infection in males increases at elderly age, because of prostate enlargement. Institutionalization and concurrent disease o 24%nursing home residents o 12% of healthy domiciliary subjects o 38% of nosocomial infection/year o >80% nosocomial UTIs due to indwelling catheters o Increased in pregnancy, spinal cord injury, diabetes mellitus, MS, HIV

Group 14 | QUIJANO, QUIMBO, QUITOY, RAMIREZ, RAMOS, L.

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PATHOGENESIS OF URINARY TRACT INFECTIONS ROUTES OF INFECTION ASCENDING INFECTION Common in females Most enter from the bowel reservoir via ascent through the urethra into the bladder2 Adherence of pathogens to the introital and urothelial mucosa plays a significant role2 Perineal soilage with feces o Mostly seen in the elderly In-dwelling catheters Spermicidal agents 2 Most common pathogen: Escherichia coli

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HEMATOGENOUS ROUTE Renal cortical abscesses Need to look for other sites of infection Most common offending agent: Staphyloccocus aureus Commonly seen in diabetes mellitus Uncommon in normal individuals2

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LYMPHATIC ROUTE Rare Contagious infections with the bowel Direct extension of bacteria from the adjacent organs via lymphatics may occur in unusual circumstances such as2 o Severe bowel infections o Retroperitoneal abscesses BACTERIAL ADHERENCE Crucial step in colonization and eventual infection Facilitated by the presence of pili that are the adhesive arms of the bacteria TYPE I (MANNOSE-SENSITIVE PILI) Both pathogenic and non-pathogenic E. coli Bacterial colonization of vaginal mucosa and bladder Mediate hemagglutination of guinea pig erythrocytes, which is inhibited by mannose causing mannose-sensitive hemoagglutination (MSHA)

Figure 1. Type I is composed of thin helical rods of FimA subunit joined to a distal tip FimH, which is responsible for adhesion to the mannosylated host receptors present in the urothelium, and it is critical to the ability of E. coli to colonize the vaginal introitus, urethra, bladder, and can cause cystitis.

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TYPE P (MANNOSE-RESISTANT PILI) Confer tropism to the kidney P for pyelonephritis Mediate hemagglutination that is not inhibited by mannose (mannoseresistant hemagglutination (MRHA))

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TYPE S Rare Binds to sialic acid residues found in both bladder and kidney epithelium

Table 1. Factors that Contribute to UTI UROPATHOGEN FACTORS HOST FACTORS  Integrity of immune system  Virulence  Foreign bodies  Load of inoculum  Functional or anatomical  Opportunistic organisms obstruction

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NATURAL HOST DEFENSES PERIURETHRAL REGION 

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Normal flora 2 o Lactobacilli o Coagulase-negative Staphylococcus aureus o Corynebacteria o Streptococci Estrogen Cervical IgA Low vaginal pH o Changes in the vaginal environment related to estrogen, cervical IgA, and low vaginal pH might alter the ability of bacteria to colonize2 Use of antibiotics o May eradicate normal flora Spermicidal agents o Frequent use of antibiotics and spermicidal agents alter the normal flora and increase the receptivity of the epithelium to uropathogens2 URINE DEFENSES Protective factors o Dilution – ↑ dilution ↓ risk of infection o Low pH – acidic urine can overcome infection o Uromodulin (Tamm-Horsfall protein) – binds to the binding sites of pili, which blocks their the adhesion to the urothelium Risk factors o Glucose facilitates infections  Consistently seen in the higher infection rates of patients with diabetes mellitus

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BLADDER DEFENSES The main protective mechanism of the bladder against infection is its ability to empty itself completely Patients with anatomical and functional obstructions are more prone to developing UTI because of significant bladder residual volume ALTERATION IN HOST DEFENSE MECHANISMS Obstruction 2 o Causes urine stasis and bacterial proliferation Vesicoureteral reflux o Predisposes an individual to recurrent infection because of urine 2 stasis Underlying disease o May render the patient immunocompromised, increasing the risk of developing infection2 Diabetes mellitus o 3 times the hospitalization for acute pyelonephritis in women 2 2 o 4 times the pyelonephritis in autopsies in diabetes mellitus Renal papillary necrosis

Group 14 |QUIJANO, QUIMBO, QUITOY, RAMIREZ, RAMOS. L.

DIAGNOSTIC PRINCIPLES PROPER URINE COLLECTION METHOD A properly collected urine specimen is key to diagnosis Retraction of foreskin (for uncircumcised men) Spreading the labia o Get midstream catch urine specimen Catheterized specimen Suprapubic tap 3 o Ideal technique but invasive o Precaution when doing a suprapubic tap:3  Proper hydration is necessary to increase bladder distention. o Indications:  Any child who is unable to void for a sample of urine. (done on pediatric patients to collect uncontaminated urine3)  Patients in retention where foley catheter insertion is difficult. DIPSTICK URINALYSIS Easy to perform Relies on color change Early detection of red and white cells Leukocyte esterase o Compound produced by the breakdown of WBCs in the urine. 3 o Has higher sensitivity. Nitrites o Produced by reduction of dietary nitrates by many gram-negative bacteria. Esterase and nitrite can be detected by a urine dipstick and are more reliable when the bacterial count is >100,000 CFU/mL.3 o Most specific3 Proteinuria Should never be used to replace a routine urinalysis which makes microscopic confirmation possible.3 MICROSCOPIC URINALYSIS 3 Correlate with dipstick urinalysis Superior to dispstick urinalysis Can be used to localize or even lead you to proper diagnosis. o Hyaline casts  Erythrocyte casts: suggest glumerulonephritis  Leukocyte casts: suggest pyelonephritis  Granular casts: advanced kidney disease  Epithelial casts: necrosis of the tubules o Crystals  Calcium oxalate  Uric acid  Triple phosphate  Cystine o Squamous epithelial cells  If there are numerous squamous epithelial cells, it suggests that the collection is poor and must be repeated.

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AUTOMATED FLOW CYTOMETER Faster turn-around time High sensitivity and specificity High positive predictive value Correlates well with cultures

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BIOCHEMICAL AND ENZYMATIC TESTS Greiss test – detects nitrite Leukocyte esterase Nitrite and leukocyte esterase  Sensitivity of 71% and a specificity of 83% Page 2 of 9

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COLONY COUNTS 100,000 col/cc is diagnostic  In asymptomatic patient, count must be >10,000 col/cc to diagnose UTI. 20-40% symptomatic women – counts 7 days o Recent UTI o Diaphragm use Treatment o Mild to moderate illness, without nausea/vomiting, outpatient therapy  Oral norfloxacin, ciprofloxacin for 10-14 days o Severe illness possible urosepsis  Parental ampicillin + gentamicin, ciprofloxacin, norfloxacin, ticarcillin-clavulanic, imipinem-cilastin, aztreonam until the fever is gone  then oral TMP/SMP, norfloxacin, ciprofloxacin, levofloxacin for 14-21 days ACUTE CYSTITIS IN PREGNANCY Pregnant women o Amoxicillin o Cephalexin o Nitrofurantoin crystals Complications of UTI IN pregnancy  Prematurity  Increased prenatal mortality  Maternal anemia COMPLICATED CYSTITIS Compromised urinary tract Very resistant pathogen Failed initial antimicrobial therapy May lead to life-threatening kidney infection Complicating host factors o Abnormalities or urinary tract o Recent urinary tract instrumentation

Group 14 |QUIJANO, QUIMBO, QUITOY, RAMIREZ, RAMOS. L.

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Recent antimicrobial agent use Diabetes mellitus Immunosuppression Pregnancy Hospital-acquired infection 4

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PROSTATITIS ACUTE PROSTATITIS Bacterial infection in the prostate gland, most commonly by urinary pathogens. Signs and symptoms o Fever o Dysuria o Perineal or back discomfort A digital rectal examination may indicate an indurated and tender gland. Brisk digital rectal examination should be avoided, as it is extremely uncomfortable for patients and is thought to cause bacteremia. Patients require a 4- to 6-week course of antibiotic therapy, typically a quinolone. o Imaging studies if no improvement in 48 hours to rule out prostatic abscess o Large abscesses managed with transurethral unroofing or percutaneous drainage. CHRONIC PROSTATITIS Signs and symptoms o Continued lower urinary tract symptoms o Pelvic pain Bacterial chronic prostatitis o Frequent cause of recurrent urinary tract infections o Treated with a prolonged course of antibiotics Chronic nonbacterial prostatitis o Does not respond to antibiotics or most other medications o Treated with biofeedback, physical therapy, and nonprostate-specific treatments Pre- and post-prostatic massage urine o Culturing method to distinguish bacterial to non-bacterial

URETHRITIS 4 Urethritis, as characterized by urethral inflammation, can result from infectious and noninfectious conditions. Symptoms (if present) o Discharge of mucopurulent or purulent material o Dysuria o Urethral pruritis Asymptomatic infections are common Etiologic agents: N. gonorrhea, C. trachomatis, Mycoplasma genitalium 4

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other

EPIDIDYMO-ORCHITIS Result of bacterial infection originating in the urinary tract. Signs and symptoms o Unilateral painful swelling of the epididymis and/or testis o Fever (often) o Erythematous scrotum on the side of involvement o Elevated WBC count (often) o +/- reactive hydrocele may be present Rapid onset Ultrasound may show increased blood flow to epididymis Treatment o Oral antibiotics if the patient is not markedly febrile and is otherwise stable.

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Hospitalization and parenteral antibiotics are required if the patient has high fevers, significantly elevated WBC, or hemodynamic instability

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Grade IV – dilation of the renal pelvis and calyces with moderate ureteral tortuosity Grade V – gross dilatation of the ureter, pelvis and calyces, ureteral tortuosity, loss of papillary impressions

UPPER URINARY TRACT INFECTIONS (KIDNEYS) Symptoms o Classic: Fever, chills, flank pain o Nausea and vomiting o Generalized body malaise Less prevalent than bladder infection Varied presentation o May be nonspecific o May be asymptomatic High index of suspicion + radiologic and lab evaluation ACUTE PYELONEPHRITIS Evaluation o Blood and urine cultures o Radiographic imaging is mandatory to rule out complicating factors Management o Oral or intravenous antibiotics o Repeat urine cultures after therapy o Drain abscess or remove focus

Figure 3. International grading of VUR according to its affectation of the ureter and pelvocalyceal system.

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Chronic Pyelonephritis Reno-cortical abscess Perinephric (retroperitoneal abscess) Ureteritis

VESICOURETERAL REFLUX Congenital anomaly caused by insufficient intramural tunneling of the distal ureter4 o Primary danger is the development of recurrent episodes of pyelonephritis – can cause cumulative renal damage through scarring Common cause of recurrent febrile UTI in children o Second most common cause of hydronephrosis after ureteropelvic junction (UPJ) obstruction4 Defect in anti-reflux mechanism o Up to two-thirds of infants presenting with urinary tract infections o Majority of cases occur in females 4 Treatment depends on severity of grade o Surgical repair with ureteral reimplantation is effective o Conservative management, consisting of antibiotic prophylaxis, may result in breakthrough infections with resistant organisms. o Submucosal injection of bulking agents at the ureteral orifice  Minimally invasive technique that may obviate the need for open surgical repair or long-term suppressive antibiotics  Not effective in every case- patients with severe reflux may still need reimplantation. Most cases could be treated medically Urologic interventions o Endoscopic injection of DEFLUX agent o Ureteral reimplantation (open, laparoscopic or robotic-assisted) if it is severe INTERNATIONAL GRADING OF VUR ACCORDING TO ITS AFFECTATION OF THE URETER AND PELVOCALYCEAL SYSTEM: o Grade I – reflux into non-dilated ureter o Grade II – reflux into the renal pelvis and calyces without dilatation o Grade III – mild/moderate dilatation of the ureter, renal pelvis and calyces with minimal blunting of the fornices

Group 14 |QUIJANO, QUIMBO, QUITOY, RAMIREZ, RAMOS. L.

Figure 4. This is a VCUG done on a child with recurrent UTI showing bilateral Grade II-III reflux on both kidneys. Note that on the left side, the calyces are still sharp while they are blunted on the right side. 3

Figure 5. A radionuclide imaging is useful in determining cortical perfusion and excretory function. This DMSA scan shows significant scarring on the left kidney.

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SPECIFIC COMPLICATED GENITOURINARY INFECTIOUS STATE XANTHOGRANULOMATOUS PYELONEPHRITIS Long-standing urinary obstruction with infection and urinary calculi that causes dysfunction of the kidney Majority are middle-aged women Destruction of renal parenchyma Staghorn in 80% of cases The following typify the findings in xanthogranulomatous PN with pararenal extension Most common etiologic agent: Proteus7

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GENITOURINARY TUBERCULOSIS Most common site of TB, after the lungs Active disease leads to renal parenchymal destruction as a result of caseation necrosis Chronic disease leads to multiple ureteral strictures (rosary beading) and a small scarred calcified urinary bladder Medical treatment is the mainstay of therapy Urologic complications are treated surgically with ureteral replacement and bladder augmentation Endemic to the Philippines, which may occur even years after an occult pulmonary tuberculosis infection.

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Figure 8. Renal Malakoplakia. Left: Cut surface of the kidney demonstrates extensive cortical and upper medullary replacement by multifocal, confluent, tumor-like masses. Right: Characterized by von Hansemman as soft, yellow-brown plaques with granulomatous lesions in which the histiocytes contain distinct basophilic inclusions or Michaelis-Gutmann bodies (represents incompletely destroyed bacteria surrounded by lipoprotein membrane.)

Figure 6. Genitourinary TB: This retrograde pyelogram shows the typical appearance of a scarred kidney with pipe stem fibrosis, rosary beading, and a kidney with a moth-eaten appearance.3        

RENAL ECHINOCOCCUS Parasitic infection caused by tapeworm Echinococcus granulosus Definitive host: dog Presents as a slowly growing tumor Most are asymptomatic Anaphylaxis may ensue when the cyst ruptures, which is highly antigenic May present as flank mass, dull pain, or hematuria Definitive diagnosis: finding hydatid cysts in the urine Treatment o Surgical drainage o Aspiration o Marsupialization o Injection of scolicidal agents o Nephrectomy

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Figure 7. Renal Echinococcus. Clockwise (A) Gross specimen. A cystic mass measuring 7 × 11 cm in lower pole. Smaller daughter cysts are identified within the larger cystic mass. (B) Gross specimen. Daughter cysts represent brood capsules that have detached and move freely. (C) Photomicrograph. Brood capsules (B) arising from the germinal layer. This CT scan shows the 2 markedly enlarged right kidney with multiple hydatid cysts. Group 14 |QUIJANO, QUIMBO, QUITOY, RAMIREZ, RAMOS. L.

RENAL MALAKOPLAKIA Malakoplakia, Greek word for “soft plaque” Usually affects the bladder, but may also affect the kidneys, lungs, bones and mesenteric lymph nodes Large histiocytes called von Hansemman cells containing MichaelisGuttman bodies Clinical Presentation o > 50 years. F:M ration is 4:1 o Debilitated, immunocompromised patients o Masses affecting bladder, ureter and kidney o Ureteral stricture, hydronephrosis o Renal vein and vena caval thrombosis o Epididymo-orchitis o May mimic prostate adenocarcinoma

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DIABETES AND UTI Gas forming or emphysematous infection is common6 o Present as fulminant infection involving the renal parenchyma o Commonly caused by E. coli Treatment o Upper tract obstruction: retrograde or antegrade tube drainage o Purulent collection: percutaneous drainage o Unstable: nephrectomy Increased incidence of UTIs in women o Both symptomatic and asymptomatic UTIs are increased women with diabetes, although there is no substantial increase in men. 3x hospitalization for acute pyelonephritis in women 4x pyelonephritis in autopsies in DM BACTERIURIA IN PREGNANCY Asymptomatic bacteriuria is one of the most common infectious complications of pregnancy. Prevalence is 2-7% Incidence increases with the duration of pregnancy Also increased in lower socioeconomic class, sickle cell traits and multiparity Anatomic and physiologic changes during pregnancy o Increase in renal size o as a result of increased blood flow o Augmented renal function o Smooth muscle atony of collecting muscle and bladder o Bladder becomes hyperemic and gets displaced There is actually a tendency for the creatinine to be lower due to dilution, so a normal creatinine in pregnant women doesn’t exclude a renal problem. Hydronephrosis in pregnant women is more common on the right since the left is cushioned by sigmoid from compression Page 7 of 9

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ACUTE PYELONEPHRITIS Bacteriuria unlikely to resolve unless treated 1-4% of all pregnant women develops acute pyelonephritis 20-40% of untreated bacteriuric patients develop acute pyelonephritis 60-75% occur in last trimester

HEMODYNAMIC (Not included in Doc’s ppt but it is in the original article)

BACTERIURIA IN ELDERLY Morbidity is significant Sepsis and shock are common Broad spectrum antibiotics Culture-guided therapy Consider drug toxicities Age related risk factors: o Decline in immunity o Neurogenic bladder dysfunction o Increased perineal soilage from incontinence o Increased catheter placement o Estrogen depletion

Table 1. Frequency of Significant Bacteriuria Related to Underlying Disease. Routine Medical examination 5% Diabetes Mellitus 20% With cystocele 23% Indwelling catheter (closed system) 37 – 50% Condom catheter (non-cooperative patient) 50% Congenital urologic disease 57% Hydronephrosis. Nephrolithiasis 85% Indwelling catheter (open system) 98%

ORGAN DYSFUNCTION

TISSUE PERFUSION

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BACTEREMIA SYSTEMIC INFLAMMATORY RESPONSE SYNDROME o Manifests as extremes of body temperature, heart rate, respiratory rate, and WBC count that occurs in response to an infection. SEPSIS SYNDROME o Progresses to shock as a result of peripheral vasodilatation caused by gram negative endotoxins o Hyperventilation: reliable early clinical indication of septicemia7 o Management of Urosepsis with Septic Shock  Resuscitation  Supportive therapy  Intensive monitoring  Broad spectrum antibiotics  Drainage and elimination of infection BACTEREMIA o Presence of viable bacteria in the bloodstream

Table 2. Diagnostic Criteria for Sepsis  Fever (core temperature >38.3°C)  Hypothermia (core temperature 90 bpm or >2 SD above the normal value for age  Tachypnea GENERAL  Altered mental status  Significant edema or positive fluid balance (>20 ml/kg over 24 h)  Hyperglycemia (plasma glucose >120 mg/dL or 7.7 mmol/L) in the absence of diabetes  Leukocytosis (WBC count >12,000 /µL ) INFLAMMA  Leukopenia (WBC count < 4000/ µL ) -TORY  Normal WBC count with >10% immature forms Group 14 |QUIJANO, QUIMBO, QUITOY, RAMIREZ, RAMOS. L.

 Arterial hypoxemia (PaO2/FIO2 4 mg/dL or 70 mmol/L)  Hyperlactatemia (>1 mmol/L)  Decreased capillary refill or mottling

(From Levy MM, Fink MP. Marshall JC., et al: 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003;31: 1250-1256)

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(Adapted from Jackson GG. Arana-Sieler JA, Andersen BR: PROFILES of PYELONEPHRITIS. Arch Intern Med 1962; 110: 663-675)

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 Arterial hypotension o SBP 70%  Cardiac index >3.5 L/min

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CATHETER-ASSOCIATED Most common cause of hospital-acquired infections Accounts for 40% of hospital infections (US) Inevitable bacteriuria results from catheterization at a rate of 10%/day Intermittent catheterization is also a risk for bacteriuria To avoid catheter infections o Aseptic technique o Closed dependent drainage o Treat symptomatic patients o Treatment based on cultures o Antimicrobials may be given x 3 days after catheter removal to avoid bacterial colonization BACTERIURIA IN SPINAL CORD INJURY UTIs are among most common urologic complication 33% have bacteriuria at any time (Strover et, 1989) Almost all become bacteriuric Many will suffer significant morbidity and mortality Bacteriuria and SCC (spinal cord compression) patients o Impaired voiding o Bladder overdistention o Increased intravesical pressure o Increased risk of obstruction o Vesicoureteral reflux o Increased instrumentation o Stones Risk factors o Decreased fluid intake o Poor hygiene o Perineal colonization o Decubitus ulcers o Evidence of local tissue trauma o Reduced host defenses Clinical presentation o Mostly asymptomatic o Fever in elderly o Catheter leakage o Increased spasticity o Malaise, lethargy

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Diagnosis o High index of suspicion o Bacteriuria AND Pyuria o Urine culture is mandatory o Pyuria alone is not diagnostic because of presence of catheter Treatment o Urine and blood cultures o Change of indwelling catheter o For afebrile patients: Oral fluoroquinolones o Febrile patients: Parenteral aminoglycosides and penicillin or third generation cephalosporin FUNGIURIA

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Risk factors o Indwelling catheters o Antimicrobial therapy o Diabetes Mellitus o Prolonged hospitalization o Immunocompromised host Clinical presentation o May affect the kidney via hematogenous spread from other sources of infection or the gastrointestinal tract. o Candida albicans (50%) o Candida glabrata (10-15%) o Fungal culture, pyuria o Fungal balls, bezoars Key Points o Remove or change catheter o Repeat cultures to guide you if the treatment is working or not o Irrigate the bladder or kidney with antifungal agent (FIRST-LINE of therapy) o If persistent infection, consider systemic therapy with Amphotericin B or Fluconazole

APPENDIX URINARY CASTS AND ASSOCIATED PATHOLOGIC CONDITIONS TYPE OF CAST

COMPOSITION

HYALINE

Macroproteins

ERYTHROCYTE

Red blood cells

LEUKOCYTE

White blood cells

EPITHELIAL

Renal tubule cells

GRANULAR WAXY FATTY BROAD

Various cell types Various cell types Lipid-laden renal tubule cells Various cell types

ASSOCIATED CONDITIONS Pyelonephritis, chronic renal disease, May be a normal finding Glomerulonephritis, May be a normal finding in patients who play contact sports Pyelonephritis, glomerulonephritis, interstitial nephritis, renal inflammatory processes Acute tubular necrosis, interstitial nephritis, eclampsia, nephrotic syndrome, allograft rejection, heavy metal ingestion, renal disease Advanced renal disease Advanced renal disease Nephrotic syndrome, renal disease, hypothyroidism End-stage renal disease

Figure 9. Fungiuria. (Left) This CT scan shows a Renal Fungus infection complicated with emphysematous pyelonephritis. Unenhanced CT scan reveals gas in the right renal collecting system (open arrow) and renal parenchyma (straight arrow). Some fungus balls were misdiagnosed as urorthelial tumors. (Right) Retrograde pyelogram reveals round filling defects in the collecting system (arrows) consistent with Mycetomas.      

KEY POINTS: URINARY TRACT INFECTION Infection of the urinary tract occurs when bacterial virulence increases and/or host defense mechanisms decrease. Early identification and treatment of complicated UTIs is essential to prevent major sequelae or death. UTI vary in presentation and sequelae. Careful diagnosis and treatment is essential. Imaging should be done whenever complicated UTI is suspected. Appropriate choice of antibiotic therapy is crucial. The majority of patients respond promptly to short courses of antimicrobial therapy

Edited by: RZ Group 14 |QUIJANO, QUIMBO, QUITOY, RAMIREZ, RAMOS. L.

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