Gram Positive Pathogens

• Staphylococcus

• Streptococcus

• Enterococcus

• Listeria monocytogenes

• Bacillus anthracis

A ‘coccus’ is a spherical bacteria

Staphylococcus tend to cluster in groups

While Streptococcus tend to line up in strings

Gram-positive bacteria: Staphylococci

Staphylococcus aureus

Staphylococcus aureus causes a variety of suppurative (pus-forming) infections and toxinoses in humans.

Important to distinguish Staphylococcus from Streptococcus

• Most Staphylococcus are resistant to Penicillin G– Most produce a -lactamase– Or, may be resistant due to mutation of PBP

(as in MRSA)

• Most Streptococcus are susceptible to Penicillin G

Lipoteichoic Acid also present

As is Polysaccharide Capsule

•Proteins that Disable Our Immune Defenses Include:

•Protein A: Binds to IgG

•Coagulase: leads to fibrin formation around bacteria, preventing phagocytosis

•Hemolysins

•Leukocidins

•Penicillinase

•Proteins that Tunnel Through Tissue Include:

•Hyaluronidase: breaks down proteoglycans in connective tissue

•Staphylokinase: Lyses formed fibrin clots

•Lipase: Degrades the fat protective layer on surface of skin

•Proease: Destroys tissue proteins

•Exotoxins Produced Include:

•Exfoliatin: causes skin to slough off (scalded skin syndrome)

•Enterotoxins: cause food poisoning (vomiting and diarrhea)

•Toxic Shock Syndrome Toxin (TSST-1): Causes massive T cell response and outpouring of cytokines, resulting in toxic shock syndrome.

3 Major Pathogenic Types of Staphylococcus:

• Staphylococcus aureus– Many types of infections

• Staphylococcus epidermidis– Most common cause of infection in indwelling prosthetic devices

(prosthetic joints, heart valves, etc.)

• Staphylococcus saprophyticus– Leading cause of urinary tract infections in sexually active young

women

Staphylococcal Scalded Skin Syndrome (SSSS)

Staphylococcus causes superficial skin lesions such as boils, styes and furunculosis;

Staphylococcus also causes more serious infections such as pneumonia, mastitis (inflammation of mammary gland), phlebitis (inflammation of vein, usually in leg), meningitis (inflammation of meninges), and urinary tract infections;

Staphylococcus also causes deep-seated infections, such as osteomyelitis (inflammation of the bone) and endocarditis (inflammation of heart).

S. aureus is a major cause of hospital acquired (nosocomial) infection of surgical wounds and infections associated with indwelling medical devices.

S. aureus causes food poisoning by releasing enterotoxins into food, and toxic shock syndrome by release of superantigens into the blood stream.

Superantigens and TSS

• http://highered.mcgraw-hill.com/sites/0072556781/student_view0/chapter32/animation_quiz_4.html

Toxic Shock Syndrome can occur via skin, vagina, or pharynx

There has been some indication that it was associated with selected materials used in some ultra-abosorbant tampons. These materials are no longer used in the US.

Treatment of Infections Caused by Staphylococcus aureus

• Antistaphylococcal penicillins: Nafcillin, oxacillin

• First Generation cephalosporins: Cefazolin

• Second Generation Cephalosporins: Cefuroxime

• Third-generation cephalosporins: Ceftriaxone, cefotaxime, ceftizoxime

-Lactam/ -lactamase inhibitor combinations: Ampicillin-sulbactam, piperacillin-tazobactam, ticarcillin-clavulanate

• Carbapenems: Imipenem, meropenem

Treatment of Infections Caused by Staphylococcus aureus (NOT methicillin resistant)

Treatment of Methicillin-resistant Staphylococcus aureus

• Vancomycin

Treatment of Methicillin-resistant Staphylococcus aureus

• Linezolid

Treatment of Methicillin-resistant Staphylococcus aureus

• Streptogramins (Quinupristin-dalfopristin)

Treatment of Methicillin-resistant Staphylococcus aureus

• Daptomycin (cubicin)

Treatment of Methicillin-resistant Staphylococcus aureus

• Tigecycline (Tygacil)

Doxycycline

Gram-positive pathogens:Streptococcus pneumoniae

Types of Streptococci

• Group A beta-Hemolytic Streptococci– Streptococcal pharyngitis (Strep throat)– Streptococcal skin infections– Scarlet Fever– Streptococcal toxic shock syndrome

– Rheumatic fever– Glomerulonephritis (inflammation of small

blood vessels in the kidney)

Streptococcus pyogenes

Streptococcus pyogenes

Impetigo

Treatment of Streptococcus pyogenes

• Penicillin G• Aminopenicillins: Ampicillin• Aminoglycosides are sometimes added for

synergy: Gentamicin

Treatment of Streptococcus pyogenes

• Clindamycin is added for severe invasive Streptococcus pyogenes infections

Treatment for Penicillin-resistant Streptococcus pyogenes (and other penicillin resistant Streptococcus)

• Vancomycin

• Second-generation cephalosporins: Cefuroxime

• Third-generation cephalosporins: cefotaxime, ceftriaxone

Necrotizing Fasciitis

Types of Streptococci (Group B)

• Viridans Group Streptococci– Dental Infections– Endocardidis

Types of Streptococci (Group D)

• Streptococcus pneumoniae

S. pneumoniae is a common cause of otitis media (ear infection) and is also a major cause of bacterial pneumonia.

Otitis media

Streptococcus pneumoniae

Treatment of Streptococcus pneumoniae

• Penicillin G (high doses)• Aminopenicillins: Ampicillin (high doses)

Ampicillin

Treatment of Penicillin-resistant Streptococcus pneumoniae

• Second Generation Cephalosoporins: Cefuroxime

• Third Generation Cephalosporins: Cefotaxime, Ceftriaxone

• Quinolones: Moxifloxacin, Levofloxacin

• Vancomycin

• Macrolides/ketolines: Telithromycin

Enterococci

Enterococcus

Enterococci are gram positive cocci, that are normal residents of the GI tract

Two common species are Enterococcus faecalis and Enterococcus faecium.

Enterococcus Resistance Mechanisms

Treatment of Infections Caused by Enterococcus

• Penicillin G• Aminopenicillins: Ampicillin• Extended-spectrum Penicillins: Piperacillin• Carbapenems: Imipenem, meropenem

Treatment of Infections Caused by Enterococcus

• For serious infections, add an aminoglycoside for synergy: Gentamicin

Treatment for Infections Caused by Penicillin-resistant Enterococci

• Vancomycin

Treatment for Vancomycin Resistant Enterococci (VRE)

• Linezolid• Tetracycline-like:

Tigecycline

Gram-positive Bacteria:Listeria Monocytogenes

Listeria monocytogenes

• http://www.nature.com/nrmicro/animation/imp_animation/index.html

Treatment of Infections Caused by Listeria monocytogenes

• Ampicillin + Gentamicin

• If penicillin allergic:– Trimethoprim-sulfamethoxazole

Bacillus anthracis

Bacillus anthracis

Bacillus anthracis

Treatment of Infections Caused by Bacillus anthracis

• Quinolones: Ciprofloxacin

Treatment of Infections Caused by Bacillus anthracis

• Tetracycline: Doxycycline

Treatment of Infections Caused by Bacillus anthracis

• For Inhalation Anthrax, a Second Agent Should be Added from the Following List:– Rifampin– Vancomycin– Penicillin G– Ampicillin– Chloramphenicol– Carbapenem: Imipenem– Clindamycin– Macrolide: Clarithromycin

Gram-negative Bacteria:Enterobacteriaceae

Septic Shock

• Septic shock is a condition of hypotension (severely reduced blood pressure) caused by decreased tissue perfusion and oxygen delivery.

• Septic shock can lead to multiple organ dysfunction syndrome and death, with the mortality rate approx. 50%.

Enterobacteriaceae

• Escherichia coli

• Salmonella

• Shigella

• Yersinia pestis

Escherichia coli

Klebsiella

Proteus

Escherichia coli.

• Link

• http://www.drkoop.com/animation/93/43.html

Treatment of Infections Caused by:E. coli., K. pneumoniae, Proteus

• Aminopenicillins: Ampicillin

• First Generation Cephalosporins: Cefazolin

• Sulfa drugs: Trimethoprim-sulfamethoxazole

• Quinolones: Ciprofloxacin, levofloxacin, moxifloxacin

Treatment of Resistant Infections Caused by:E. coli., K. pneumoniae, Proteus

• Third Generation Cephalosporins: Cefoxaxime, ceftriaxone, ceftizoxime

• Monobactam: Aztreonam

Treatment of Resistant Infections Caused by: E. coli., K. pneumoniae, Proteus

• Extended Spectrum penicillins + -lactamase inhibitor: Piperacillin-tazobactam, ticarcillin-clavulanate

Treatment of Resistant Infections Caused by: E. coli., K. pneumoniae, Proteus

• Carbapenems: Imipenem, meropenem, ertapenem

• Carbapenem + aminoglycoside in serious infections: Add Gentamicin, Tobramycin, amikacin

Meropenem

Treatment of Infections Caused by:Enterobacter, Serratia, Citrobacter, Providencia, and Morganella Spp.

• Carbapenems: Imipenem, meropenem, ertapenem

• Sulfa Drugs: Trimethoprim-sulfamethoxazole

• Quinolones: Ciprofloxacin, levofloxacin• Fourth Generation Cephalosporins:

Cefepime• + aminoglycoside: Gentamicin,

tobramycin, amikacin

Treatment of Infections Caused by:Salmonella enterica, Shigella spp.

• Quinolones: Ciprofloxacin

• Third-generation cephalosporins: Cefotaxime, ceftriaxone, ceftizoxime

• Macrolides: Azithromycin

Treatment of Infections Caused by:Yersinia spp.

• Aminoglycosides: Gentamicin, streptomycin

Gentamycin

Treatment of Infections Caused by:Yersinia spp.

Treatment of Infections Caused by:Yersinia spp.

• Tetracyclines: Doxycycline

Treatment of Infections Caused by:Yersinia spp.

•Quinolones: Ciprofloxacin•Sulfa drugs

Gram-negative Bacteria:Pseudomonas

Pseudomonas

Pseudomonas aeruginosa

Resistance of Pseudomonas

Treatment of Infections caused by Pseudomonas aeruginosa

• Extended spectrum penicillins: Piperacillin, Ticarcillin

• Third Generation Cephalosporins: Ceftazidime• Fourth-generation Cephalosporins: Cefepime• Carbapenems: Imipenem, meropenem• Monobactams: Aztreonam• Quinolones: Ciprofloxacin, Levofloxacin• Aminoglycosides: Gentamicin, tobramycin,

amikacin

Treatment of Serious Infections Caused by Pseudomonas aeruginosa

• Antipseudomonal -lactam + aminoclycoside: Ceftazidime + Tobramycin

Treatment of Serious Infections Caused by Pseudomonas aeruginosa

• Extended-spectrum penicillin + antipseudomonal quinolone: Piperacillin + Ciprofloxacin

Neisseria

Neisseria meningitidis

• The meninges are a series of membranes surrounding the central nervous system

• They consist of three layers: the dura matter, the arachnoid matter, and the pia matter

Neisseria meningitidis

Neisseria meningitidis

Neisseria gonorrhoeae

Neisseria gonorrhoeae

Treatment of Infections Caused by Neisseria meningitidis

• Penicillin G

• Third generation cephalosporins: Ceftriaxone, cefotaxime

Treatment of Infections Caused byNeisseria Gonorrhoeae

• Third Generation Cephalosporins: Ceftriaxone, cefixime

Curved Gram Negative Bacilli

– Campylobacter jejuni, – Helicobacter pylori, – Vibrio cholerae

Campylobacter jejuni

Campylobacter jejuni

Treatment of Infection Caused by Campylobacter jejuni

• Macrolides: Erythromycin, azithromycin, clarithromycin

• Link

Azithromycin

Treatment of Infection Caused by Campylobacter jejuni

• Quinolones: Ciprofloxacin

Helicobacteri pylori

Helicobacter pylori

Helicobacter pylori

Duodenal Peptic Ulceration Caused by Helicobacter pylori

Treatment of Infection Caused by Helicobacter pylori

• Amoxicillin + clarithromycin + proton pump inhibitor

• Metronidazole + clarithromycin + proton pump inhibitor

• Bismuth subsalicylate + metronidazole + tetracycline + proton pump inhibitor

Vibrio cholerae

Vibrio cholerae

Cholera Epidemic in Zimbabwe Continues to Worsen

Vibrio cholerae

Treatment of Infection Caused by Vibrio cholerae

• Tetracyclines: tetracycline, doxycycline

• Sulfa drugs: Trimethoprim-sulfamethoxazole

• Quinolones: Ciprofloxacin

• Macrolides: Erythromycin, Azithromycin

Haemophilus influenzae

Haemophilus influenzae

• Since the organism was frequently isolated from the lungs of patients during the 1890 and 1918 influenza pandemics, scientists incorrectly concluded that the bacterium was the causative agent.

•Haemophilic means ‘blood loving’. The organism requires a blood-containing medium for growth•Influenzae: The bacterium often attacks the lungs of a patient with viral influenza.

Haemophilus influenzae

Haemophilus influenzae

Treatment of Infections Caused by Haemophilus influenzae

• Aminopenicillins + -lactamase inhibitor:– Amoxicillin/clavulanate– Ampicillin/sulbactam

• Second-generation cephalosporin– Cefuroxime

• Third-generation cephalosporin– Ceftriaxone– Cefotaxime

Bordetalla pertussis

Bordetalla pertussis

• Bordetalla pertussis causes a violent cough called ‘whooping cough’

Bordetella pertussis

Treatment of Infection Caused by Bordetella pertussis

• Macrolides: Azithromycin, Clarithromycin, Erythromycin

Moraxella catarrhalis

• Causes otitis media, pneumonia, and sinusitis

• Usually produces -lactamase

Treatment of Infections Caused by Moraxella catarrhalis

• Extended spectrum penicillins: piperacillin, ticarcillin

-lactam/-lactamase inhibitor combinations: piperacillin/tazobactam, ticarcillin/clavulanate

• Second and third-generation cephalosporins

Acinetobacter

• Recent outbreak among soldiers in Iraq

• Second leading cause of infection among troops during the Vietnam conflict

Acinetobacter

Treatment of Infection Caused by Acinetobacter

• Sulbactam

• Carbapenems

• Quinolones

Anaerobic BacteriaGram positive: Clostridia spp.

Clostridium tetani

• Clostridium tetani is the etiologic agent of tetanus

• Characterized by persistent tonic spasm, usually involving the masseter muscles (lockjaw)

• Usually caused by deep wound becoming infected with C. tetani spores.

Clostridium botulinum

• Clostridium botulinum is usually acquired by ingestion of food contaminated with C. botulinum spores

• Botulinum toxin leads to cranial neuroopathies and weakness rather than muscular spasm.

• Link

Botulinum Toxin (Botox)

• Botulinum toxin is a neurotoxic protein produced by Clostridium botulinum

• It was discovered in the 1950’s that injecting small amounts decreased muscle activity by blocking release of acetylcholine at the neuromuscular junction

Botulinum Toxin (Botox)

LINK

Treatment of Infections Caused by Clostridium spp.

• Penicillin G

• Metronidazole (may be associated with better outcomes

Clostridium difficile

Clostridium difficile

Treatment of Infections Caused by Clostridium difficile

• Oral metronidazole

• Oral vancomycin

Clostridium perfringens is the cause of gas gangrene

Gas Gangrene

• Gangrene comes from the Greek ‘gangraina’ meaing ‘putrefication of tissues’

• Dry gangrene often occurs in the toes and feet of elderly patients

• Wet gangrene occurs in naturally moist tissues, such as the mouth, bowel, lungs.

• Gas gangrene is due to infection by Clostridium perfringens, which produces gas within the tissues.

• Such gas-producing infection spreads very rapidly, and should be considered a medical emergency.

Treatment of Infections Caused by Clostridium perfringens

• Penicillin + one of the following:– Clindamycin– Tetracycline– Metronidazole

Hyperbaric Oxygen Therapy

One treatment for gas gangrene includes hyperbaric oxygen therapy

Anaerobic Gram-negative Bacteria

Common Anaerobic Gram-negative Pathogens

• Bacteroides fragilis– Usually produces -lactamase

• Prevotella

• Porphyromonas

Treatment of Anaerobic Gram-negative Infections

-lactam/-lactamase inhibitor combinations– Ampicillin-sulbactam– Piperacillin-tazobactam– Ticarcillin-clavulanate

• Carbapenems: Imipenem, Meropenem, Ertapenem

• Metronidazole

Atypical Bacteria: Chlamydia

Chlamydia trachomatis

• One of the most common sexually transmitted diseases

• Also a leading cause of blindness in some parts of the world

Chlamydia trachomatis

Chlamydia is a bacterial infection of the genital tract spread through sexual contact. If untreated, it can result in various medical complications, including damage to the reproductive organs.

The disease affects both women and men, although reported cases for women greatly exceed those for men. Chlamydia affects people in all age groups, but it is particularly prevalent among teenagers and young adults. According to the U.S. Centers for Disease Control and Prevention (CDC), the infection is most prevalent among women aged 20 to 25.

Chlamydia trachomatis

Some signs and symptoms that may be present in people infected with chlamydia are:

• Abnormal discharge from the penis or vagina• Burning sensation during urination• Lower abdominal or back pain• Nausea• Fever• Pain during intercourse• Burning or itching around the head of the penis• Swollen or tender testicles• Bleeding between menstrual cycles• Proctitis (inflammation of the rectum)

Life Cycle of Chlamydia trachomatis

Link

Treatment of Infections Caused by Chlamydia trachomatis

• Tetracyclines– Tetracycline– Doxycycline

• Macrolides– Azithromycin– Erythromycin– Telithromycin

• Quinolones– Ofloxacin– Moxifloxacin– Gemifloxacin

Mycoplasma pneumoniae

Mycoplasma pneumoniae

Treatment of Infections Caused by Mycoplasma pneumoniae

• Macrolides: Azithromycin, clarithromycin, erythromycin telithromycin

• Tetracyclines: Tetracycline, doxycycline

• Quinolones: Levofloxacin, moxifloxacin, gemifloxacin

Atypical Bacteria: Legionella

• Legionella pneumophila is the most common species, and is the causative agent of Legionaires’ disease

• Once in the lung, Legionella organisms are taken up by macrophages and multiply within them.

Legionalla pneumophila

• http://www.nature.com/nrmicro/animation/imp_animation/index.html

Treatment of Infections Caused by Legionella pneumophila

• Macrolides: Azithromycin

• Quinolones: Levofloxacin, moxifloxacin

Brucella

• Brucellosis is a disease of animals, that is occasionally transmitted to humans

• Contact with animals and/or ingestion of unpasteurized milk or cheese are risk factors

Brucella

Brucella

Treatment of Infections Caused by Brucella spp.

• Doxycycline + rifampin

• Doxycycline + gentamicin

• Doxycycline + streptomycin

Francisella tularensis

Francisella tularensis

Treatment of Infections Caused by Francisella tularensis

• Aminoglycosides: Streptomycin, Gentamicin

• Tetracyclines: Tetracycline, doxycycline

Rickettsia spp

Rickettsia rickettsii

Rocky Mountain spotted fever is the most severe and most frequently reported rickettsial illness in the United States. The disease is caused by Rickettsia rickettsii, a species of bacteria that is spread to humans by ixodid (hard) ticks.

Treatment of Infections Caused by Rickettsia spp.

• Tetracyclines– Doxycycline– Tetracycline

Spirochetes: Treponema pallidum

Treponema pallidum

Treponema pallidum

Treponema pallidum

Treatment of Infections Caused by Treponema pallidum

• Penicillin G (including benzathine penicillin)

• Tetracyclines

• Third Generation Cephalosporins

Penicillin procainePenicillin benzathine

These particular salts of penicillin are injected intramuscularly and absorbed slowly over a period of time.

Penicillin G benzathine

Procaine penicillin G

http://www.chemblink.com/products/54-35-3.htm

Borrelia borgdorferi

Borrelia burgdorferi

Borrelia burgdorferi is the causative agent of Lyme Disease

Treatment of Infections Caused by Borrelia burgdorferi

• Tetracyclines: Doxycycline

• Aminopenicillins: Amoxicillin

Leptospira interrogans

Leptospira interrogans

Treatment of Infection Caused by Leptospira interrogans

• Tetracyclines: Doxycycline

• Aminopenicillins: Amoxicillin

• Severe Disease can be treated with Penicillin G, Ampicillin, or Ceftriaxone

Mycobacteria

• Mycobacterium tuberculosis

• Mycobacterium avium complex

• Mycobacterium leprae

Mycobacterium tuberculosis

Link

Mycobacterium tuberculosis

Mycobacterium tuberculosis

Treatment of Infections Caused by Mycobacterium tuberculosis

• Active Disease– Isoniazid + Rifampin + Pyrazinamide +

Ethambutol for two months– Followed by: Isoniazid + Rifampin for Four

months

• Latent Disease– Isoniazid for 9 months

Mycobacterium avium complex

Mycobacterium avium complex

Treatment of Infections Caused by Mycobacterium avium complex (MAC)

• Clarithromycin + ethambutol + rifabutin

Mycobacterium leprae

Mycobacterium leprae

Leprosy

Treatment of Infections Caused by Mycobacterium leprae

• Dapsone + rifampin + clofazimine