southeast Asia: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Infect Dis.
harmful? Clin Infect Dis. 2015;60(6):847–848.
Ann Intern Med. 2005;142(10):805–812.
Pennington H. Escherichia coli O157. Lancet. 2010;376(9750):1428–1435.
Infect Dis. 1999;34(3):229–243.
Mead PS, Griffin PM. Escherichia coli O157:H7. Lancet. 1998;352(9135):1207–1212.
traveler’s diarrhea. Antimicrob Agents Chemother. 1992;36(12):2821–2824.
syndrome and death among hospitalized patients. Clin Infect Dis. 2001;33(7):923–931.
J Pediatr. 2002;141(2):172–171.
laboratories. MMWR Recomm Rep. 2009;58(RR-12):1–14.
serologic, clinical, and epidemiologic findings. J Infect Dis. 2001;183(7):1063–1070.
related disorders. Kidney Int. 2006;70(3):423–431.
infections: with focus on the day of illness. Epidemiol Infect. 2000;124(3):343–349.
Tarr PI et al. Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet.
O157:H7 infections. N EnglJ Med. 2000;342(26):1930–1936.
Infect Dis. 1998;177(4):962–966.
home. N EnglJ Med. 1987;317(24):1496–1500.
review. BMC Public Health. 2013;13:799.
syndrome. J Pediatr. 1990;116(4):589–592.
Escherichia coli O157:H7 infection? Aliment Pharmacol Ther. 2006;24(5):731–742.
O157 infection in FoodNet Sites. Clin Infect Dis. 2011;52(9):1130–1132.
O157:H7 Infections. Pediatrics. 1997;100(1):e12–e12.
Bartlett JG. Antibiotic-associated diarrhea. N EnglJ Med. 2002;346(5):334–339.
Freeman J et al. The changing epidemiology of clostridium difficile infections. Clin Microbiol Rev.
Chemother. 2008;62(2):388–396.
Pharmacol Ther. 2009;31(7):754–759.
McDonald LC et al. An epidemic, toxin gene–variant strain of clostridium difficile. N Engl J Med.
rapid testing, severe infection, and mortality. Clin Infect Dis. 2015;61(2):233–241.
Clin Infect Dis. 2008;46(10):1489–1492.
the role of infection caused by clostridium difficile. Clin Infect Dis. 2002;34(12):1585–1592.
Gastroenterol. 2013;108(4):478–498;quiz 499.
Infect Control Hosp Epidemiol. 2007;28(4):377–381.
Bartlett JG. Antibiotic-associated diarrhea. Clin Infect Dis. 1992;15(4):573–581.
diarrhea: a cohort study during an epidemic in Quebec. Clin Infect Dis. 2005;41(9):1254–1260.
Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America
(IDSA). Infect Control Hosp Epidemiol. 2010;31(5):431–455.
before and after the emergence of NAP1/027. Am J Gastroenterol. 2007;102(12):2781–2788.
diarrhea and colitis. Lancet. 1983;2:1043.
Tedesco F et al. Oral vancomycin for antibiotic-assocaited psedumembranous colitis. Lancet.
Control Hosp Epidemiol. 2010;31(5):431–455.
Antimicrob Agents Chemother. 2002;46(6):1647–1650.
metronidazole. Clin Pharm. 1986;5(12):999–1000.
of two dosage regimens. Am J Med. 1989;86(1):15–19.
diarrhoea. BMJ. 1978;2(6153):1667–1669.
the treatment of Clostridium difficile infection. Pharmacotherapy. 2015;35(2):119–126.
difficile infections: a meta-analysis and indirect treatment comparison. J Antimicrob Chemother.
Louie TJ et al. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med.
Am J Health Syst Pharm. 2012;69(11):933–943.
treatment of Clostridium difficile-associated disease. Am J Health Syst Pharm. 1998;55:1407.
Int J Antimicrob Agents. 2009;33(1):4–7.
Sullivan A. Probiotics in human infections. J Antimicrob Chemother. 2002;50(5):625–627.
randomised double blind placebo controlled trial. BMJ. 2007;335(7610):80.
Munoz P et al. Saccharomyces cerevisiae Fungemia: an emerging infectious disease. Clin Infect Dis.
life. J Pediatr Gastroenterol Nutr. 2010;51(1):2–7.
EnglJ Med. 2000;342(6):390–397.
diarrhea and cost. Ann Intern Med. 1998;128(12, part 1):989.
Infect Control Hosp Epidemiol. 2002;23(11):653–659.
magic? Clin Infect Dis. 2008;46(10):1493–1498.
a prospective, randomized, double-blinded trial. Clin Infect Dis. 1997;24(3):324–333.
center in southeastern USA. Infection. 2010;38(4):297–300.
Furuya-Kanamori L et al. Comorbidities, exposure to medications, and the risk of community-acquired
metronidazole. Ann Intern Med. 1992;117(4):297.
Intern Med. 2006;166(22):2518.
difficile infection. JAMA Intern Med. 2015;175(5):784–791.
Clin Infect Dis. 2002;34(3):346–353.
setting: a multistate model. Infect Control Hosp Epidemiol. 2015;36(9):1024–1030.
complications. Ann Surg. 2002;235(3):363–372.
Lamp KC et al. Pharmacokinetics and pharmacodynamics of the nitroimidazole antimicrobials. Clin
Pharmacokinet. 1999;36(5):353–373.
associated colitis due to Clostridium difficile. Gut. 1986;27(10):1169–1172.
and review of the literature. Clin Infect Dis. 2002;35(6):690–696.
Control Hosp Epidemiol. 1999;20(1):43–50.
Saginur R et al. Colitis associated with metronidazole therapy. J Infect Dis. 1980;141(6):772–774.
retrospective study of more than 2000 patients. J Investig Med. 2015;63(5):747–751.
difficile diarrhoea. Lancet. 2001;357(9251):189–193.
McPherson S et al. Intravenous immunoglobulin for the treatment of severe, refractory, and recurrent
clostridium difficile diarrhea. Dis Colon Rectum. 2006;49(5):640–645.
diarrhea. Am J Infect Control. 2007;35(2):131–137.
Quebec, Canada. Clin Infect Dis. 2006;42(6):758–764.
disease. Am J Gastroenterology. 2002;97(7):1769–1775.
Am J Gastroenterol. 1985;80:867.
course of cholestyramine. Pediatr Infect Dis J. 1989;8:175.
vancomycin and rifampin. J Clin Gastroenterol. 1987;9(2):155–159.
antibiotics for clostridium difficile disease. JAMA. 1994;271(24):1913.
high dose vancomycin combined with saccharomyces boulardii. Clin Infect Dis. 2000;31(4):1012–1017.
vancomycin and rifaximin. Clin Infect Dis. 2007;44(6):846–848.
pilot study. J Clin Gastroenterol. 2009;43(1):91–92.
difficile infection. Antimicrob Agents Chemother. 2015;59(11):7007–7010.
infection. J Antimicrob Chemother. 2014;69(11):2901–2912.
Intern Med. 2015;162(9):630–638.
unit. J Intensive Care Med. 2016;31(9):577–586.
clostridium difficile infection: a multicenter experience. J Clin Gastroenterol. 2016;50(5):398–402.
infection. Infect Control Hosp Epidemiol. 2015;36:438–444.
Acute cholecystitis is the acute inflammation of the gallbladder,
presenting with fever, prolonged abdominal pain, and positive Murphy’s
sign of the right upper quadrant followed by nausea and vomiting. Acute
cholangitis is an acute inflammation of the common bile duct with
accompanying classic Charcot’s triad: fever, jaundice, and right upper
Empiric therapy for severe biliary tract infections may include
combination therapy with either ciprofloxacin, levofloxacin, or cefepime
plus metronidazole or monotherapy with piperacillin/tazobactam or an
antipseudomonal carbapenem (imipenem/cilastatin, meropenem,
doripenem) if multidrug-resistant gram-negative rods are suspected.
Spontaneous bacterial peritonitis (SBP) is largely a monomicrobial
infection commonly caused by aerobic enteric gram-negative rods, such
as Escherichia coli and Klebsiella pneumoniae.
Empiric therapy for SBP may include a third-generation cephalosporin
such as ceftriaxone or cefotaxime or parenteral fluoroquinolone with
activity versus Streptococcus pneumoniae. Length of therapy depends
on the reduction of polymorphonuclear leukocyte counts (<250 cells/μL)
in peritoneal fluid, generally occurring in 5 days or fewer.
culture. Blood cultures may be useful, however, in health care–
associated infections for detection of gram-positive cocci, yeast, or
multidrug-resistant pathogens.
Therapy for secondary peritonitis should include antimicrobial coverage
directed at gram-negative bacteria and anaerobes. Therapy may include
(a) certain extended-spectrum β-lactams or β-lactamase inhibitor
combinations, (b) carbapenems, or (c) a fluoroquinolone with
Duration of therapy for intra-abdominal infections typically ranges from
4 to 7 days. Clinical response and source control influence duration of
Acute penetrating abdominal trauma requires a short course (<24 hours) Case 70-7 (Question 2)
of antimicrobial therapy. Delay of therapy or development of infection
necessitates a 5 to 7-day course of therapy.
Despite the introduction of new antimicrobial agents and improvements in diagnostic
and surgical techniques, the treatment of intra-abdominal infections remains a
therapeutic challenge. However, advances in radiographic and interventional
techniques with timely source control, improved fluid and nutritional management,
and the selection of appropriate antimicrobial agents have decreased mortality in
Intra-abdominal infections are those contained within the peritoneal cavity, which
extends from the undersurface of the diaphragm to the floor of the pelvis or the
retroperitoneal space. Intra-abdominal infections can present as a localized infection
(e.g., appendicitis), a diffuse inflammation throughout the peritoneum (peritonitis), or
anywhere within the abdomen, between bowel loops, or in solid organs such as the
liver, biliary tract, spleen, pancreas, or female pelvic organs.
Empiric antimicrobial therapy should be initiated as soon as an intra-abdominal
infection is suspected. Therapy should be selected on the basis of the suspected
pathogens; however, antimicrobial therapy alone is insufficient, especially in the
setting of diffuse peritonitis. Source control is a term used to involve all physical
measures needed to eradicate an infection, such as debridement of necrotic tissue or
drainage of an abscess or fluid collection. If adequate source control is delayed,
bacteremia, multiple organ failure, and mortality are more likely to occur.
1 The bacterial population of the stomach can be altered
by drugs or diseases that increase gastric pH or decrease gastric motility. Not
surprisingly, patients with bleeding or obstructing duodenal ulcers, gastric ulcers,
gastric carcinomas, or those receiving proton pump inhibitors or histamine-2
receptor antagonists have an increased number of oral bacteria colonizing the
The upper small intestine (duodenum and jejunum) usually contains relatively few
bacteria and harbors mainly oral flora. The lower small intestine serves as a
transitional zone between the sparsely populated stomach and the abundant microbial
In the ileum, facultative gram-negative and gram-positive species, as well as
obligate anaerobes, are encountered. As the distal ileum is approached, the quantity
and variety of bacteria increase. Substantial numbers of anaerobic bacteria are
present, including Bacteroides species, as well as Escherichia coli and Enterococcus
In the large bowel, anaerobic bacteria, particularly Bacteroides species,
predominate. In the distal colon, bacterial counts average 10
anaerobes outnumbering other organisms by a ratio of 1,000 to 10,000:1.
facultative aerobes, E. coli is the most frequently isolated species.
differences in regional microflora populations, it is not surprising that trauma to the
colon carries a much higher risk of intra-abdominal infection in comparison with the
Resistant flora are more common in health care–associated infections, including
Pseudomonas aeruginosa, Acinetobacter species, extended-spectrum β-lactamases
Figure 70-1 Microflora of the gastrointestinal tract.
Common Pathogens in Intra-Abdominal Infection
Disease Common Pathogens Comments
Cholecystitis, cholangitis E. coli, Klebsiella pneumoniae,
infections and chronic surgical
infections, particularly in patients
Primary peritonitis E. coli, K. pneumoniae,
bacterial peritonitis presented in
Secondary peritonitis E. coli, Bacteroides fragilis,
Generally polymicrobial with both
aerobic and anaerobic pathogens.
Enterococcus species should be
considered in the setting of health
diphtheroids, gram-negative rods
intraperitoneal antibiotics must be a
INFECTIONS OF THE BILIARY TRACT
Cholecystitis and cholangitis originate as inflammatory conditions, usually as a result
of obstruction in the gallbladder or common bile duct. The obstruction is typically
caused by the presence of stones. The biliary tract is sterile under normal conditions,
and the flow of bile, along with its bacteriostatic properties, functions to maintain the
sterility. Infection typically occurs as a secondary event to obstruction.
Acute cholecystitis is the acute inflammation of the gallbladder. The presence of
gallstones in greater than 90% of cases prevents the outflow of gallbladder drainage
by obstructing the neck of the gallbladder, Hartmann’s pouch, or the cystic duct.
obstruction causes an increase in intraluminal pressure, gallbladder distension, and
edema, which triggers an acute inflammatory response. The potential consequences
of this obstruction and inflammation include infection, ischemia, perforation, and
11 The reduction in gallbladder outflow leads to biliary stasis, which
provides an ideal environment for bacterial proliferation and subsequent infection
Acute cholangitis is an acute inflammation of the common bile duct. The most
common cause of cholangitis in the United States is common bile duct obstruction as
a consequence of choledocholithiasis. Less common causes include neoplastic
obstruction, postoperative obstruction after biliary intervention, benign strictures,
and primary sclerosing cholangitis.
4 The decrease in biliary outflow results in biliary
stasis and bacterial proliferation. Infection results in a rapid rise in biliary pressure,
which facilitates the spread of bacteria into lymphatics and the bloodstream via
alterations in membrane permeability. In comparison with cholecystitis, acute
cholangitis generally carries a poorer prognosis.
Figure 70-2 Pathogenesis of acute cholecystitis.
CLINICAL PRESENTATION AND DIAGNOSIS
laboratory values are the following:
White blood cell (WBC) count, 17 × 10
Serum creatinine (SCr), 1.1 mg/dL
What evidence of cholangitis exists in D.S.? How does the presentation of cholecystitis differ from
The clinical manifestations of acute cholangitis vary, but the classic presentation
involves Charcot’s triad, which consists of fever, jaundice, and right upper quadrant
abdominal pain. Fever is present in 90% of cases, and jaundice and abdominal pain
4 A smaller percentage of patients, generally with
gram-negative septicemia, may present with changes in mental status and
4 Laboratory findings of acute cholangitis include leukocytosis, elevated
bilirubin (>2 mg/dL), and alkaline phosphatase, and mildly elevated liver
13 The clinical signs and symptoms of cholangitis, as exemplified by
D.S., include high fevers (38.9°C), chills, jaundice, and right upper quadrant
abdominal pain. Laboratory evidence supportive of cholangitis includes leukocytosis
/μL, increased bilirubin of 6 mg/dL, and elevated alkaline
The clinical presentation of acute cholecystitis involves fever and prolonged
constant abdominal pain typically localized to the right upper quadrant, followed by
nausea and vomiting. On physical examination, tenderness in the right upper quadrant
and a positive Murphy’s sign (inspiration is inhibited by pain on palpation) are often
11 Laboratory findings include leukocytosis with increased neutrophils (left
shift) and mild elevations in transaminases. Jaundice is less common in patients with
cholecystitis (bilirubin <4 mg/dL) compared with cholangitis.
Diagnostic imaging for acute cholecystitis and cholangitis involves
ultrasonography. Findings for acute cholecystitis may reveal pericholecystic fluid,
distension of the gallbladder, thickening of the gallbladder wall, stones, and a
14 Ultrasound is less sensitive for choledocholithiasis, but
it may reveal biliary dilation with stones. Hepatobiliary scintigraphy is another
diagnostic tool used to identify obstruction of the cystic duct. After intravenous
injection with technetium hepatobiliary iminodiacetic acid (Tc-HIDA), failure to
observe gallbladder filling suggests acute cholecystitis.
(CT) imaging may be superior in determining the extent of biliary obstruction.
Endoscopic retrograde cholangiopancreatography (ERCP) is an alternative mode of
CASE 70-1, QUESTION 2: What are the most likely organisms causing infection in D.S.? What clinical
specimens are helpful to identify the causative pathogen(s)?
The most common pathogens associated with acute cholangitis include E. coli,
Klebsiella species, and Enterobacter species. However, P. aeruginosa, skin flora
(Staphylococcus species, Streptococcus species), and oropharynx bacteria may be
implicated. Anaerobic organisms, commonly Bacteroides species, are associated
with approximately 15% of infections, particularly in elderly patients undergoing
15 The etiology of cholecystitis typically involves E. coli,
Klebsiella species, and Enterococcus species. Anaerobes are less commonly
As described above, the stasis of bile flow results in proliferation of bacteria
within the gallbladder or common bile duct. Acute cholangitis results in increased
pressure within the common bile duct with dissemination of bacteria from the biliary
tree to the bloodstream. Blood cultures may be positive in up to 40% of patients with
symptomatic acute cholangitis.
4 Acute cholecystitis may reveal positive bile cultures
in 20% to 75% of patients with symptomatic disease, but the utility of bile cultures
In contrast to cholangitis, bacteremia is unlikely with
cholecystitis. The choice of antibacterial agents is largely empiric covering the
aforementioned common causative pathogens.
Definitive therapy for both cholangitis and cholecystitis must involve source control,
using surgery, percutaneous drainage, or endoscopic intervention. Empiric
antibacterial therapy should be added owing to the likelihood of secondary infection
and to prevent complications. Supportive measures include fluid and electrolyte
supplementation and analgesia.
To decompress or drain the biliary ductal system in cholangitis, ERCP is used
with a success rate of greater than 90% in the treatment of cholangitis.
percutaneous transhepatic biliary drainage or endoscopic sphincterotomy can be used
to drain the contents. Open surgery is a less favored option to decompress the biliary
tree as it is associated with increased mortality.
4 Acute symptomatic cholecystitis
requires removal of the gallbladder (cholecystectomy). The procedure of choice is
laparoscopic cholecystectomy within 48 to 72 hours of onset of symptoms. Early
intervention is associated with decreased morbidity and length of hospital stay
compared with delayed surgical intervention.
In high-risk patients, in whom the
risks outweigh the benefits of early surgery, percutaneous cholecystostomy can be
performed to drain the contents of the gallbladder. The procedure improves the
clinical symptoms in 75% to 90% of patients who cannot undergo surgery.
Cholecystectomy, however, should take place once the patient is stable enough for
CASE 70-1, QUESTION 3: Based on the most likely causative pathogen(s), what empiric antimicrobial
therapy is recommended for D.S., given a diagnosis of cholangitis?
Empiric antimicrobial therapy for acute cholangitis and cholecystitis should be
initiated after blood cultures have been collected. The empiric choice of therapy
should cover enteric gram-negative pathogens, particularly E. coli (Table 70-2).
general, the addition of anaerobic coverage is not mandatory for cholecystitis;
however, it should be considered in the setting of severe cases such as acute
cholangitis, biliary-enteric anastomosis, or health care–associated infections.
Empiric coverage for Enterococcus species should be considered for patients at risk
for health care–associated infections, such as immunocompromised patients, patients
6 Antimicrobial therapy must be guided by drug
pharmacokinetics and pharmacodynamics, local resistance patterns, and patient
factors, such as drug allergies, renal or hepatic dysfunction, and cost.
Considering their activity versus multidrug-resistant gram-negative bacilli,
carbapenems generally should be reserved for infection caused by these pathogens.
Vancomycin may be added empirically in health care–associated biliary infections in
which ampicillin-resistant enterococci and MRSA are of concern. Linezolid or
daptomycin may be considered in cases of known vancomycin-resistant Enterococcus
species (VRE). Empiric broad-spectrum antimicrobial regimens should be narrowed,
when possible, based on culture and susceptibility findings. For mild-to-moderate
community-acquired acute cholecystitis, monotherapy with cefazolin, cefuroxime, or
ceftriaxone is recommended. Because of a wide prevalence of ampicillin–sulbactam
resistant E. coli, this agent is no longer recommended for empiric use.
to fluoroquinolones is problematic with unpredictable susceptibility of E. coli to
ciprofloxacin and levofloxacin.
16 Current guidelines for complicated intra-abdominal
infections (cIAI) suggest fluoroquinolones be considered for therapy when
institutional antibiograms indicate greater than 90% susceptibility of E. coli.
aminoglycosides is not routinely recommended because of the need for therapeutic
drug monitoring and potential nephrotoxicity and ototoxicity.
comparison with other regimens, aminoglycoside-based regimens are inferior in the
treatment of intra-abdominal infections.
17 However, some argue the decreased
efficacy of aminoglycosides has been caused by inadequate dosing. An appropriate
empiric regimen for D.S. would be piperacillin–tazobactam 3.375 g intravenously
Treatment Options for Intra-Abdominal Infections
Infection Agents and Regimens Agent Dosing
Community-acquired perforated or
Cefoxitin 2 g IV every 6 hours
Ertapenem 1 g IV every 24 hours
Tigecycline 100 mg initially then 50
Cefazolin 1–2 g IV every 8 hours
Ceftriaxone 1–2 g IV every 12–24
Ciprofloxacin 400 mg IV every 12
Levofloxacin 750 mg IV every 24
Moxifloxacin 400 mg IV every 24
Metronidazole 500 mg IV every 8–
physiologic disturbance, advanced
Acute cholangitis associated with
Health care–associated intraabdominal infections
Cefepime 1-2 g IV every 8 hours
Ceftazidime 1-2 g IV every 8-12
Piperacillin–tazobactam 3.375 g IV
every 4–6 hours or 4.5 g IV every
every 6 hours or 1 g every 8 hours
Meropenem 1 g IV every 8 hours
every 8–12 hours (normal renal
Ceftazidime/avibactam 2.5 g IV
Ceftolozane/tazobactam 1.5 g IV
Metronidazole 500 mg IV every 8–
aSelection of fluoroquinolones should be based on local antibiogram or susceptibility reports.
methicillin-resistant Staphylococcus aureus or ampicillin-resistant enterococcal infection).
eExtended infusion: 3.375 g IV every 8 hours over 4 hours
CASE 70-1, QUESTION 4: The physician caring for D.S. questions the need for an antibiotic that
Common bile duct obstruction prevents the entry of antibiotics into the bile, and
the need for high biliary concentrations of antibiotics in the treatment of cholangitis
19 concluded that a number of antibiotics with
excellent in-vitro susceptibility, but poor biliary excretion, are still clinically
effective. Biliary antibacterial concentrations do not correlate with an improved
4 Highly biliary-excreted versus moderately biliary-excreted
antibiotics have been compared.
18 Serum concentrations are more important than
biliary levels in reducing the septic complications of biliary tract surgery.
Furthermore, biliary excretion of any antibiotic is minimal in the presence of
The treatment of D.S.’s biliary tract infection must include biliary drainage.
Piperacillin–tazobactam should be continued for 4 to 7 days.
Peritonitis is inflammation of the peritoneum as a result of infectious or chemical
inflammation within the peritoneal cavity.
Infectious peritonitis can be classified
as primary, secondary, or tertiary. Primary peritonitis involves the development of
infection in the peritoneal cavity in the absence of intra-abdominal pathology.
Secondary peritonitis classically results from contamination of the peritoneum with
gastrointestinal (GI) or genitourinary microorganisms as a result of the loss of
mucosal barrier integrity. Tertiary peritonitis is clinical peritonitis along with signs
of sepsis and multi-organ dysfunction persisting or recurring after the treatment of
Primary peritonitis is also known as spontaneous bacterial peritonitis (SBP) and is
most frequently identified in adults with cirrhosis and ascites. Nearly 10% to 30% of
hospitalized patients with cirrhosis and ascites have SBP.
associated with post-necrotic cirrhosis, chronic acute hepatitis, acute viral hepatitis,
congestive heart failure, metastatic malignancy, or systemic lupus erythematosus.
Spontaneous Bacterial Peritonitis in Cirrhotic Patients
CLINICAL MANIFESTATIONS AND DIAGNOSIS
Patients with SBP may present with fever, signs of peritonitis, including abdominal
pain, altered mental status, changes in GI motility, nausea, vomiting, diarrhea, or
22 Fever is common, occurring in 50% to 80% of patients.
an atypical presentation or even lack symptoms.
22 The diagnosis of SBP is made on
clinical presentation and examination of the peritoneal fluid via paracentesis. The
ascitic fluid is tested for cell counts with WBC differential, and the presence of
microorganisms is based on Gram stain and culture. Ascitic fluid with an elevated
polymorphonuclear (PMN) count (≥250/μL) is diagnostic for SBP.
Comments
Post a Comment
اكتب تعليق حول الموضوع