A CASE REPORT A 3 yr old female child who had undergone chemotherapy for ALL a few weeks back A 3 yr old female child who had undergone chemotherapy for ALL a few weeks back Now Presented with c/o  Ear discharge- 5 days duration  Vulvar necrotic lesion 2 days duration O/E  Toxic appearance  Fever, tachycardia, tachypnoea  Hypotension  A single vulvar necrotic lesion  Other similar lesions on thoracic region & lower extremities

Investigations  Total WBC – 1600/mm 3 (N-0%, L-64%, M- 32%)  Hb- 8.5 g/dl  CRP- 190 mg/dl  Electrolyte imbalance (hypokalemia, hyponatremia)  Blood culture& wound swab sent for c/s Initial treatment given  Ionotropic support with norepinephrine  Mechanical ventilation  Empirical antibiotic therapy with Pipzo, Amikacin & Clindamycin Pipzo, Amikacin & Clindamycin

 Surgical debridement of necrotic lesion was done Blood culture & wound swab report was sent to microbiology lab for culture & sensitivity Blood culture & wound swab report  Pseudomonas aeruginosa grown in culture sensitive to pipzo, Imipenem, Tobramycin

PSEUDOMONAS INFECTIONS

Pseudomonas spp. Pseudomonas spp. Structure and Physiology Structure and Physiology  Gram-negative rods.  Motile with polar flagella.  Obligate aerobe.  Oxidase-positive.  Do not ferment carbohydrates.  Minimal nutritional reqts  Survive where most organisms cannot; cannot;  Resistant to multiple drugs.

P. aeruginosa Forms round colonies with a fluorescent greenish color, sweet odor, and beta hemolysis. Pyocyanin- nonfluorescent bluish pigment; pyoverdin- fluorescent greenish pigment; pyorubin (red) pyomelanin (black) Some strains have an exo polysaccharide capsule.(alginate)

Epidemiology Wide spread in nature Wide spread in nature  commonly present in moist environments in hospitals (respiratory equipments, cleaning solutions, sinks,bath tubs, toilets, endoscopes, flowers etc.)

 Pathogenic when host defences are compromised  P. aeruginosa can infect almost any external site or organ, mostly acquired in the hospital esp in ICUs  One of the most common causes of hospital acquired pneumonia & wound infections. Pathogenesis Rarely cause disease in healthy host, Rarely cause disease in healthy host, But is highly virulent when host defences are compromised But is highly virulent when host defences are compromised

Factors predisposing to Pseudomonas aeruginosa infections DISRUPTION OF CUTANEOUS/ MUCOSAL BARRIERS: Burn injury Cystic fibrosis Dermatitis Penetrating trauma Surgery ET intubation Catheterization Injection drug use IMMUNO SUPPRESSION Neutropenia WBC defects Antibody defects Defective CMI Extremes of age Diabetes mellitus Steroid therapy Cancer AIDS DISRUPTION OF NORMAL BACTERIAL FLORA Broad spectrum antibiotic therapy Exposure to hospital environment

Virulence factors associated with Pseudomonas infection STRUCTURAL COMPONENTS STRUCTURAL COMPONENTS Capsule Capsule Mucoid polysaccharide Mucoid polysaccharide inhibits antibiotic (aminoglycoside) killing; inhibits antibiotic (aminoglycoside) killing; Inhibits phagocytosis Inhibits phagocytosis Pili Pili Adhesin Adhesin Lipopolysaccharide Lipopolysaccharide Endotoxin activity Endotoxin activity Pyocyanin Pyocyanin Impairs ciliary function; Impairs ciliary function; mediates tissue damage through production of toxic oxygen radicals mediates tissue damage through production of toxic oxygen radicals

Virulence factors cont.. Virulence factors cont.. TOXINS AND ENZYMES TOXINS AND ENZYMES Exotoxin A Exotoxin A Inhibits protein synthesis; produces tissue damage (e.g., skin, cornea); Inhibits protein synthesis; produces tissue damage (e.g., skin, cornea); Immunosuppressive Immunosuppressive Exotoxin S Exotoxin S Inhibits protein synthesis; Cytotoxin (leukocidin) Cytotoxin (leukocidin) Cytotoxic for eukaryotic membranes Cytotoxic for eukaryotic membranes

Virulence factors contd… Virulence factors contd… Elastase Elastase Destruction of elastin-containing tissues (e.g., blood vessels, lung tissue, skin), collagen, immunoglobulins, and complement factors Destruction of elastin-containing tissues (e.g., blood vessels, lung tissue, skin), collagen, immunoglobulins, and complement factors Alkaline protease, Phospholipase C Alkaline protease, Phospholipase C causes tissue damage; causes tissue damage;

ANTIBIOTIC RESISTANCE is also a virulence factor Mechanisms of Antibiotic Resistance in Pseudomonas aeruginosa

INFECTIONS CAUSED BY PSEUDOMONAS 1) Pulmonary infections 2) Skin infections 3) Urinary Tract Infections 4) Ear infections 5) Eye infections 6) Bacteremia & Endocarditis

1. Pulmonary Infections  Asymptomatic colonization  Tracheobronchitis  Severe necrotizing bronchopneumonia. Colonization is seen in patients with Colonization is seen in patients with cystic fibrosis, cystic fibrosis, other chronic lung diseases, other chronic lung diseases, Neutropenia Neutropenia Pt on ventilator Pt on ventilator (Ventilator associated pneumonia) (Ventilator associated pneumonia)

Patients with cystic fibrosis Patients with cystic fibrosis Mucoid strains are commonly isolated from such patients and are difficult to eradicate with antibiotic therapy. Mucoid strains are commonly isolated from such patients and are difficult to eradicate with antibiotic therapy. The mortality rate is as high as 70%. The mortality rate is as high as 70%.

2. Primary skin infections A) Burn wound infection common in patients with severe burns. common in patients with severe burns. Colonization of a burn wound Colonization of a burn wound localized vascular damage localized vascular damage tissue necrosis tissue necrosis bacteremia bacteremia

Predisposing factors for burn infections Predisposing factors for burn infections 1. The moist surface of the burn wound 2. Lack of a neutrophilic response to tissue invasion invasion

B) Folliculitis results from immersion in contaminated water (e.g., hot tubs, whirlpools, swimming pools). results from immersion in contaminated water (e.g., hot tubs, whirlpools, swimming pools).

C) Fingernail infections in people whose hands are frequently exposed to water. in people whose hands are frequently exposed to water. Secondary infections with Pseudomonas occur in people who have acne or who depilate their legs occur in people who have acne or who depilate their legs

3. Urinary tract Infection in patients with long-term indwelling urinary catheters in patients with long-term indwelling urinary catheters Exposure to broad spectrum antibiotics selects for multi drug resistant bacteria. 4. Ear Infections A) Otitis externa A) Otitis externa swimming an important risk factor ("swimmer's ear"). managed with topical antibiotics

B) Malignant otitis externa B) Malignant otitis externa Virulent form of disease seen in diabetic and elderly patients. Virulent form of disease seen in diabetic and elderly patients. Invades the underlying tissues,damage the cranial nerves and bones, can be life threatening. Invades the underlying tissues,damage the cranial nerves and bones, can be life threatening. Aggressive, antimicrobial and surgical intervention is required for patients Aggressive, antimicrobial and surgical intervention is required for patients

C) Chronic otitis media.

Eye Infections Infections of the eye occur after initial trauma to the cornea (e.g., abrasion from contact lens, scratch on the eye surface) and then exposure to P. aeruginosa in contaminated water. and then exposure to P. aeruginosa in contaminated water. Corneal ulcers develop and can progress to eye- threatening disease unless prompt treatment is instituted

Bacteremia and Endocarditis. Mortality rate in affected patients is higher with P. aeruginosa bacteremia because of Mortality rate in affected patients is higher with P. aeruginosa bacteremia because of 1. The predilection of the organism for immunocompromised patients 2. The inherent virulence of Pseudomonas.

Bacteremia occurs most often in patients with Neutropenia, Neutropenia, Diabetes mellitus, Diabetes mellitus, Extensive burns, Extensive burns, Hematologic malignancies. Hematologic malignancies. Most bacteremias originate from infections of the Lower respiratory tract, Lower respiratory tract, Urinary tract, and Urinary tract, and Skin and soft tissue (particularly burn wound infections). Skin and soft tissue (particularly burn wound infections).

Ecthyma gangrenosum Characteristic skin lesions in pseudomonas bacteremia. Characteristic skin lesions in pseudomonas bacteremia. Erythematous vesicles that become hemorrhagic, necrotic, and ulcerated. Erythematous vesicles that become hemorrhagic, necrotic, and ulcerated.

Pseudomonas endocarditis Most commonly observed in intravenous-drug abusers. Most commonly observed in intravenous-drug abusers. Acquire the infection from the use of drug paraphernalia contaminated with the waterborne organisms. Acquire the infection from the use of drug paraphernalia contaminated with the waterborne organisms. The tricuspid valve is often involved, The tricuspid valve is often involved, The infection is associated with a chronic course The infection is associated with a chronic course

Other Infections  Gastrointestinal tract infections  Central nervous system infections  Musculoskeletal system The underlying conditions required for most infections are The underlying conditions required for most infections are  (1) The presence of the organism in a moist reservoir reservoir  (2) The circumvention or elimination of host defenses defenses

Gastrointestinal infections.  Any part of the git from the oropharynx to the rectum can be affected  Primarily in immunocompromised individuals. Presents as Presents as  Pediatric diarrhea,  Typical gastroenteritis,  Necrotizing enterocolitis.  Important portal of entry in Pseudomonas septicemia Pseudomonas septicemia & bacteremia & bacteremia

Central nervous system infections. Central nervous system infections. Meningitis and brain abscesses. Meningitis and brain abscesses. Invades the CNS from a contiguous structure such as the inner ear or paranasal sinus, Invades the CNS from a contiguous structure such as the inner ear or paranasal sinus,or Inoculated directly by means of head trauma, surgery or invasive diagnostic procedures, Inoculated directly by means of head trauma, surgery or invasive diagnostic procedures,or Spreads from a distant site of infection such as the urinary tract. Spreads from a distant site of infection such as the urinary tract.

Laboratory Diagnosis  Specimen: skin lesions, pus, urine, blood, spinal fluid, sputum.  Culture: Blood agar plate and Differential media (MacConkey agar)

Identification of P. aeruginosa is usually based on Colonial morphology, Colonial morphology, β-hemolysis, β-hemolysis, Oxidase positivity, Oxidase positivity, Characteristic pigments Characteristic pigments Sweet odor, Sweet odor, Growth at 42 C. Growth at 42 C.

Treatment The antimicrobial therapy for Pseudomonas infections is frustrating because The antimicrobial therapy for Pseudomonas infections is frustrating because  (1) the bacteria are typically resistant to most antibiotics  (2) the infected patient with compromised host defenses cannot augment the antibiotic activity  Combined antibiotic therapy is generally required to avoid resistance.. Avoid using inappropriate broad-spectrum antibiotics, which can suppress the normal flora and permit overgrowth of resistant pseudomonads

Some Antipseudomonadal antibiotics: Piperacillin, Piperacillin/tazobactam (Penicillins) Piperacillin, Piperacillin/tazobactam (Penicillins) Ceftazidime (Cephalosporins) Ceftazidime (Cephalosporins) Imipenem, meropenem (carbapenems) Imipenem, meropenem (carbapenems) Tobramycin, Amikacin, Gentamicin (Aminoglycosides) Tobramycin, Amikacin, Gentamicin (Aminoglycosides) Ciprofloxacin (Quinolones) Ciprofloxacin (Quinolones) Polymyxin B, Colistin Polymyxin B, Colistin

PREVENTION & CONTROL  Its impossible to eliminate Pseudomonas from the hospital environment. Effective infection-control practices should concentrate on preventing the  Contamination of sterile equipment, such as respiratory therapy and dialysis machines,  Cross-contamination of patients by medical personnel.  The inappropriate use of broad-spectrum antibiotics should also be avoided

Pseudomonas and related organisms Other Aerobic nonfermenters Burkholderia cepacia: RT infection in cystic fibrosis patients, UTI, opportunistic infections Burkholderia pseudomallei: opportunistic pulmonary infections Stenotrophomonas maltophilia: opportunistic infections Acinetobacter baumannii: opportunistic infections of respiratory tract infections Moraxella catarrhalis: opportunistic RT infections

CASE REVIEW Diagnosis Pseudomonas aeruginosa Sepsis in a child with neutropenia associated with Ecthyema gangrenosum Pseudomonas aeruginosa Sepsis in a child with neutropenia associated with Ecthyema gangrenosum Pipzo was continued as per AST report Pipzo was continued as per AST reportOUTCOME Successful completion of 2 wks course of antimicrobial therapy Successful completion of 2 wks course of antimicrobial therapy Complete recovery and healing of necrotic lesions Complete recovery and healing of necrotic lesions