Gram Positive Bacteria


Article Author:
Omeed Sizar


Article Editor:
Chandrashekhar Unakal


Editors In Chief:
Anantha Padmanabhan
Aakash Gajjar
Burt Cagir


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Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes
Komal Shaheen
Sandeep Sekhon


Updated:
6/4/2019 2:27:29 PM

Introduction

Health professionals need to understand the important difference between gram-positive and gram-negative bacteria. Gram-positive bacteria are bacteria classified by the color they turn in the staining method. Hans Christian Gram developed the staining method in 1884. The staining method uses crystal violet dye which is retained by the thick peptidoglycan cell wall found in gram-positive organisms. This gives gram-positive organisms a blue color when viewed under a microscope. Although gram-negative organisms classically have an outer membrane, they have a thinner peptidoglycan layer which does not hold the blue dye used in the initial dying process. Other information used to differentiate bacteria is the shape. Gram-positive bacteria comprise of cocci, bacilli, or branching filaments.

Etiology

Gram-positive cocci include Staphylococcus (catalase positive) which grows clusters and Streptococcus (catalase negative) which grows in chains. The staphylococci are further subdivided into coagulase positive (S. aureus) and coagulase negative (S. epidermidis and S. saprophyticus) species. Streptococcus bacteria are divided into: Strep. pyogenes (Group A), Strep. agalactiae (Group B), Enterococci (Group D), Strep viridans, and Strep pneumonia.

Gram-positive bacilli (rods) are divided their ability to produce spores. Bacillus and Clostridia are spore-forming rods while Listeria and Corynebacterium are not. Spore-forming rods that produce spores can survive in environments for many years. Also, the ranching filament rods encompass Nocardia and actinomyces. 

Gram-positive organisms have a thicker peptidoglycan cell wall compared with gram-negative bacteria. It is a 20-80nm thick polymer while the peptidoglycan layer of the gram-negative cell wall is 2 to 3nm thick and covered with an outer lipid bilayer membrane.

Epidemiology

Bloodstream infection mortality rates have increased by 78% in just two decades[1]. Gram-positive organisms have a highly variable growth and resistance patterns. The SCOPE project (Surveillance and Control of Pathogens of Epidemiologic Importance) found that gram-positive organisms in those with an underlying malignancy accounted for 62% of all bloodstream infections in 1995 and for 76% in 2000 while gram-negative organisms accounted for 22% and 14% of infections for these years[2]

Pathophysiology

Gram-positive Cocci:

Staphylococcus aereus is a gram-positive, catalase positive, coagulase positive cocci in clusters. S. aureus can cause inflammatory diseases including skin infections, pneumonia, endocarditis, septic arthritis, osteomyelitis, and abscesses. S aureus can also cause toxic shock syndrome (TSST-1), scalded skin syndrome (exfoliative toxin, and food poisoning (enterotoxin). 

Staphylococcus epidermidis is a gram-positive, catalase positive, coagulase negative cocci in cluster. Novobiocin sensitive. S. epidermidis commonly infects prosthetic devices and IV catheters producing biofilms. Staphylococcus saprophyticus is novobiocin resistant and is a normal flora of the genital tract and perineum. S. saprophyticus accounts for the second most common cause of uncomplicated UTI. 

Streptococcus pneumoniae is a gram-positive, encapsulated, lancet-shaped diplococci most commonly causing otitis media, pneumonia, sinusitis, and meningitis. Streptococcus viridans consist of Strep. mutans and Strep mitis found in normal flora of the oropharynx commonly causing dental carries and subacute bacterial endocarditis (Strep. sanguinis).

Streptococcus pyogenes is a gram-positive group A cocci which can cause pyogenic infections (pharyngitis, cellulitis, impetigo, erysipelas), toxigenic infections (scarlet fever, necrotizing fasciitis), and immunologic infections (glomerulonephritis and rheumatic fever). ASO titer detects S. pyogenes infections.

Streptococcus agalactiae is a gram-positive group B cocci which colonize the vagina and is found mainly in babies. Pregnant women need to be screened with GBS at 35-37 weeks of gestation. 

Enterococci is a gram-positive group D cocci found mainly in the colonic flora and can cause biliary tract infections and UTIs. Vancomycin-resistant enterococci (VRE) are an important cause of nosocomial infections. 

Gram-positive rods:

Clostridia is a gram-positive spore-forming rod consisting C tetani, C botulinum, C perfringes, and C difficile. C difficile is often secondary to antibiotic use (clindamycin/ampicillin), PPI use, and recent hospitalization. Treatment involves primarily with oral vancomycin.

Bacillus anthracis is a gram-positive spore-forming rod that produces anthrax toxin resulting in an ulcer with a black eschar. Bacillus cereus is a gram-positive rod that can be acquired from spores surviving under-cooked or reheated rice. Symptoms include nausea, vomiting, and watery non-bloody diarrhea. 

Corynebacterium diphtheria is a gram-positive club-shaped rod which can cause pseudomembranous pharyngitis, myocarditis, and arrhythmias. Toxoid vaccines prevent diphtheria.

Listeria monocytogenes is a gram-positive rod acquired by ingestion of cold deli meats and unpasteurized dairy products or by vaginal transmission during birth. Listeria can cause neonatal meningitis, meningitis in immunocompromised patients, gastroenteritis, and septicemia. Treatment includes ampicillin. 

History and Physical

It is important to identify patients with sepsis and order necessary blood cultures and labs. 

Physical

  • Bullous impetigo
  • Draining sinus tracts
  • Erythema
  • Fever
  • Murmur if endocarditis is present
  • Petechiae if toxic shock syndrome is present
  • Superficial abscesses
  • Warmth

Evaluation

Once a gram-positive organism infection is suspected, these laboratory studies are useful:

  • CBC
  • Electrolytes
  • Blood cultures
  • Pro-calcitonin level
  • Echocardiogram if endocarditis is suspected
  • Joint aspiration if a septic joint is suspected

Treatment / Management

Penicillin was the first antibiotic ever introduced during World War II by Alexander Fleming in 1928. Penicillin doesn't cover Staph or Enterococcus but used mainly streptococcal infections. The Penicillinase-resistant organisms (Naficillin, oxacillin, cloxacillin, dicloxacillin) cover Staph (MSSA) and Strep. Anti-pseudomonal penicillins include piperacillin and ticarcillin effective against gram positive, gram negative, pseudomonas, and anaerobes. Carbapenems cover gram-positives, gram negatives, and anaerobes. [3][4][5]

Bactrim, Clindamycin, and Doxycycline are oral antibiotics used for mild to moderate MRSA infections. It is important to note that Bactrim increases coumadin levels leading to increased INR. Vancomycin, Linezolid, Daptomycin, Synercid, and Tigecycline cover moderate to the severe community and hospital-acquired MRSA. Vancomycin should be renally dosed with trough levels between 15-20. Linezolid is very expensive and should only be used if a patient is allergic to Vancomycin. CBC needs to be checked weekly to avoid bone marrow suppression, neutropenia, thrombocytopenia, and anemia. Linezolid, Daptomycin, and Tigecycline are used to treat VRE or Vancomycin-resistant enterococci. [6][7][8]

Prognosis

The prognosis following infection with gram-positive organisms is variable. The highest mortality rates are seen in elderly persons who tend to have suppressed immune systems and less physiologic reserve.

Enhancing Healthcare Team Outcomes

Health professionals including doctors, nurses, and pharmacists need to be aware of risk factors to properly treat patients with selected antibiotics. Pharmacists need to properly monitor vancomycin trough levels to avoid mortality in patients with Staph aureus. An interprofessional approach will produce the best outcomes. [Level V]

Outcomes: Screening for methicillin-resistant Staphylococcus aureus (MRSA) risk factors enhance infection control. MRSA risk factors include patients who are above age 65, urinary catheter, previous antibiotic treatment past three months, trauma, and those admitted from a long-term facility[9]. [Level V]


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Gram Positive Bacteria - Questions

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After gram stain, how do gram-positive bacteria appear?

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Which of following is found exclusive in Gram-positive bacteria?



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Which cell wall structure determines the Gram staining characteristics of a bacterium?



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Which of the following organisms is Gram positive?



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A 34-year-old male with no past medical history presents complaining of multiple symptoms including difficulty swallowing, chest pain, and sore throat for worsening past two weeks. Blood culture grows gram-positive club-shaped rods. Which bacteria is responsible for the patient's symptoms?



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Gram Positive Bacteria - References

References

Callejo-Torre F,Eiros Bouza JM,Olaechea Astigarraga P,Coma Del Corral MJ,Palomar Martínez M,Alvarez-Lerma F,López-Pueyo MJ, Risk factors for methicillin-resistant Staphylococcus aureus colonisation or infection in intensive care units and their reliability for predicting MRSA on ICU admission. Le infezioni in medicina : rivista periodica di eziologia, epidemiologia, diagnostica, clinica e terapia delle patologie infettive. 2016 Sep 1     [PubMed]
Wisplinghoff H,Seifert H,Wenzel RP,Edmond MB, Current trends in the epidemiology of nosocomial bloodstream infections in patients with hematological malignancies and solid neoplasms in hospitals in the United States. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2003 May 1     [PubMed]
National Nosocomial Infections Surveillance (NNIS) system report, data summary from January 1992-April 2000, issued June 2000. American journal of infection control. 2000 Dec     [PubMed]
Righi E,Carnelutti A,Bassetti M, Current role of oxazolidinones and lipoglycopeptides in skin and soft tissue infections. Current opinion in infectious diseases. 2019 Jan 16;     [PubMed]
Zamoner W,Prado IRS,Balbi AL,Ponce D, Vancomycin Dosing, Monitoring and Toxicity: Critical review of the clinical practice. Clinical and experimental pharmacology     [PubMed]
Rogalla D,Bomar PA, Listeria Monocytogenes 2018 Jan;     [PubMed]
Rostkowska KA,Szymanek-Pasternak A,Simon KA, Spontaneous bacterial peritonitis - therapeutic challenges in the era of increasing drug resistance of bacteria. Clinical and experimental hepatology. 2018 Dec;     [PubMed]
Gashaw M,Berhane M,Bekele S,Kibru G,Teshager L,Yilma Y,Ahmed Y,Fentahun N,Assefa H,Wieser A,Gudina EK,Ali S, Emergence of high drug resistant bacterial isolates from patients with health care associated infections at Jimma University medical center: a cross sectional study. Antimicrobial resistance and infection control. 2018;     [PubMed]
Bolia IK,Tsiodras S,Chloros GD,Kaspiris A,Sarlikiotis T,Savvidou OD,Papagelopoulos PJ, A Review of Novel Antibiotic Regimens for the Treatment of Orthopedic Infections. Orthopedics. 2018 Nov 1;     [PubMed]

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