Staphylococcus

Background

This is a ubiquitous organism which has been associated with nearly every disease syndrome in nearly every organ. Staphylococcus was once susceptible to many antibiotics, including penicillin. However, rapid evolution and acquisition of resistance to these antibiotics led to improved, extended spectrum antibiotics, the most common of which is methicillin. However, the emergence of methicillin-resistant Staphylococcus (MRSA) is now a major epidemiological and treatment concern both in the community and hospital setting.

OUTLINE

Epidemiology

Disease Associations

Pathogenesis

Laboratory/Radiologic/Other Diagnostic Testing

Gross Appearance and Clinical Variants

Prognosis and Treatment

Commonly Used Terms

EPIDEMIOLOGY CHARACTERIZATION

GEOGRAPHY

MRSA

An epidemiological study of methicillin-resistant Staphylococcus aureus (MRSA) isolated from medical staff, inpatients, and hospital environment in one ward at our hospital.

Nishijima S, Sugimachi T, Higashida T, Asada Y, Okuda K, Murata K.

Department of Dermatology, Kansai Medical University, Osaka, Japan.
J Dermatol 1992 Jun;19(6):356-61 Related Articles, Books, LinkOut

An epidemiological study of methicillin-resistant Staphylococcus aureus (MRSA) isolated from medical staff, inpatients, and hospital environment in one ward at our hospital.

Nishijima S, Sugimachi T, Higashida T, Asada Y, Okuda K, Murata K.

Department of Dermatology, Kansai Medical University, Osaka, Japan.

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most important causative microorganisms for nosocomial infections. Recently, the incidence of isolation of MRSA has been increasing every year in Japan and is, notably, much more frequently found in inpatients than in outpatients. Therefore, we have done epidemiological studies of MRSA isolated from medical staff, inpatients, and the hospital environment in one ward of our hospital. Thereafter, we examined the antibiotic susceptibility (ABPC, DMPPC, CET, CMZ, IPM, GM, MINO, OFLX, EM, CLDM, VCM), phage typing, and coagulase typing of these MRSA. MRSA were isolated more frequently from anterior nares of inpatients than from doctors and nurses. MRSA were isolated more frequently from the environment near carriers of MRSA. Coagulase type II and phage type N.T. (not typable) were the dominant types of MRSA in our hospital (69% and 61%). MRSA strains were resistant to most antibiotics with a few exceptions (VCM, IPM, CMZ, CET). The high isolation frequency of MRSA in our hospital seems to suggest that inpatients who are carrying MRSA spread MRSA throughout the hospital environment and that the anterior nares of inpatients are the major MRSA harbor.

Effect of delayed infection control measures on a hospital outbreak of methicillin-resistant Staphylococcus aureus.

Harbarth S, Martin Y, Rohner P, Henry N, Auckenthaler R, Pittet D.

Infection Control Programme, Department of Internal Medicine, University of Geneva Hospitals, Geneva, Switzerland.
J Hosp Infect 2000 Sep;46(1):43-9 Abstract quote
All patients positive for methicillin-resistant Staphylococcus aureus (MRSA) at the University Hospitals of Geneva, Switzerland, between 1989 and 1997 (N = 1771) were included in a cohort study to evaluate the consequences of delayed containment of a hospital-wide outbreak occurring during a 4-year absence of MRSA control measures.

The effects of efforts to control both the MRSA reservoir and the number of bacteraemic patients were assessed. Intensive infection control measures were initiated in 1993 and included patient screening, on-site surveillance, contact isolation, a computerized alert system, and hospital-wide promotion of hand hygiene. An increase in the rate of new MRSA-infected or -colonized patients was observed between 1989 and 1994 (from 0.05 to 0.60 cases per 100 admissions), which subsequently decreased to 0.24 cases in 1997 (P<0.001). However, the proportion of laboratory-documented methicillin-resistant isolates among all S. aureus showed little variation in the years from 1993 onwards (range, 19-24%), reflecting the result of an increase in the number of screening cultures. The annual number of patients with MRSA bacteraemia strongly correlated with the hospital-wide prevalence of MRSA patients (R(2)= 0.60; P = 0.01) and the rate of new MRSA patients (R(2)= 0.97; P<0.001).

Consequently, the attack rate of nosocomial MRSA bacteraemia served as an excellent marker for the MRSA patient reservoir. In conclusion, despite delayed implementation, infection control measures had a substantial impact on both the reservoir of MRSA patients and the attack rate of MRSA bacteraemia.

Nationwide survey shows that methicillin-resistant Staphylococcus aureus strains heterogeneously and intermediately resistant to vancomycin are not disseminated throughout Japanese hospitals.

Ike Y, Arakawa Y, Ma X, Tatewaki K, Nagasawa M, Tomita H, Tanimoto K, Fujimoto S.

Department of Microbiology, Gunma University School of Medicine, Maebashi, Gunma 371-8511, Japan.
J Clin Microbiol 2001 Dec;39(12):4445-51 Abstract quote
A total of 6,625 methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates obtained from 278 hospitals throughout Japan were obtained between November and December 1997 and were examined for their sensitivities to vancomycin using Mueller Hinton (MH), brain heart infusion (BHI), agar plates, or the broth microdilution method.

A concentrated inoculum of an MRSA strain or the use of highly enriched medium, such as BHI medium, allows an individual cell to grow on agar plates containing a vancomycin concentration greater than the MIC for the parent strain. However, cells of the colonies which grew on BHI agar plates containing the higher vancomycin concentrations did not acquire a level of vancomycin resistance greater than that of the parent strain and were not subpopulations of heterogeneously vancomycin-resistant MRSA. There was no significance in the fact that these colonies grew on the higher concentration of vancomycin: none showed stable resistance to vancomycin at a concentration above the MIC for the parent strain, and no cell from these colonies showed a relationship between the MIC and the ability of these colonies to grow on higher concentrations of vancomycin. The vancomycin MIC was not above 2 microg/ml for any of the cells originating from these colonies. No Mu3-type heterogeneously resistant MRSA strains, which constitutively produce subpopulations from MRSA clinical isolates with intermediate vancomycin resistance at a high frequency, were detected.

There was a unipolar distribution of the MICs ranging from 0.25 to 2 microg of vancomycin/ml among the 6,625 MRSA clinical isolates, indicating that there was no Mu50-type intermediately vancomycin-resistant MRSA (MIC, 8 microg/ml by National Committee for Clinical Laboratory Standards criteria) among the clinical isolates, and there was no evidence of dissemination of Mu3-type MRSA heteroresistant to vancomycin.

The Nottingham Staphylococcus aureus population study: prevalence of MRSA among the elderly in a university hospital.

Hori S, Sunley R, Tami A, Grundmann H.

Division of Microbiology and Infectious Diseases, Queen's Medical Centre, University Hospital Nottingham, Nottingham, UK.
J Hosp Infect 2002 Jan;50(1):25-9 Abstract quote
A prevalence survey of methicillin-resistant Staphylococcus aureus (MRSA) in elderly patients (65 years and older) three weeks after admission to a university hospital was performed. Risk factors associated with hospital MRSA carriage were determined.

The design was a cross-sectional patient-based study and all adult wards at the University Hospital Nottingham (1600 beds) were included. Three hundred and forty-two elderly individuals (65 years and older) were enrolled into the study on day 21 after admission. One hundred and twenty patients [35.08% (95% confidence intervals 29.93-40.25%)] carried S. aureus. MRSA was isolated from 54 patients. The MRSA prevalence was 158/1000 (95% CI 119-197/1000 patients). Independent risk factors for MRSA carriage in the hospital were exposure to ampicillin [adjusted odds ratio 4.1 (95% CI 1.28-13.14)] and ciprofloxacin [17.1 (95% CI 2.91-99.90)]. Forty-one MRSA isolates (75.9%) belonged to the epidemic type EMRSA 15, seven isolates to EMRSA 16 (12.9%) and six isolates were sporadic strains as determined by genetic typing. It can be expected that among this defined risk group, between 187 and 331 patients carried MRSA on discharge in the year 2000. MRSA carriage is frequent and detected in only 15% of actual carriers amongst elderly patients by routine clinical investigations three weeks after admission.

The only significant risk factor identified by multivariate logistic regression was antibiotic chemotherapy. The repeated finding of a strong association between MRSA colonization and previous ciprofloxacin exposure demands attention and indicates that fluoroquinolones should be used prudently in institutions where MRSA is endemic.

DISEASE ASSOCIATIONS CHARACTERIZATION

PATHOGENESIS CHARACTERIZATION

MRSA
(METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS)

The evolutionary history of methicillin-resistant Staphylococcus aureus (MRSA).

Enright MC, Robinson DA, Randle G, Feil EJ, Grundmann H, Spratt BG.

Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, United Kingdom.
Proc Natl Acad Sci U S A 2002 May 28;99(11):7687-92 Abstract quote
Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of hospital-acquired infections that are becoming increasingly difficult to combat because of emerging resistance to all current antibiotic classes. The evolutionary origins of MRSA are poorly understood, no rational nomenclature exists, and there is no consensus on the number of major MRSA clones or the relatedness of clones described from different countries.

We resolve all of these issues and provide a more thorough and precise analysis of the evolution of MRSA clones than has previously been possible. Using multilocus sequence typing and an algorithm, BURST, we analyzed an international collection of 912 MRSA and methicillin-susceptible S. aureus (MSSA) isolates. We identified 11 major MRSA clones within five groups of related genotypes. The putative ancestral genotype of each group and the most parsimonious patterns of descent of isolates from each ancestor were inferred by using BURST, which, together with analysis of the methicillin resistance genes, established the likely evolutionary origins of each major MRSA clone, the genotype of the original MRSA clone and its MSSA progenitor, and the extent of acquisition and horizontal movement of the methicillin resistance genes.

Major MRSA clones have arisen repeatedly from successful epidemic MSSA strains, and isolates with decreased susceptibility to vancomycin, the antibiotic of last resort, are arising from some of these major MRSA clones, highlighting a depressing progression of increasing drug resistance within a small number of ecologically successful S. aureus genotypes.

LABORATORY/RADIOLOGIC/
OTHER TESTS
CHARACTERIZATION

RADIOLOGIC

LABORATORY MARKERS

GENERAL

Evaluation of Three Techniques for Detection of Low-Level Methicillin-Resistant Staphylococcus aureus (MRSA): a Disk Diffusion Method with Cefoxitin and Moxalactam, the Vitek 2 System, and the MRSA-Screen Latex Agglutination Test.

Felten A, Grandry B, Lagrange PH, Casin I.

Service de Bacteriologie-Virologie-Hygiene, Hopital Saint-Louis, 75475 Paris Cedex 10, France.
J Clin Microbiol 2002 Aug;40(8):2766-71 Abstract quote
Very-low-level methicillin-resistant Staphylococcus aureus (MRSA), or class 1 MRSA, is often misdiagnosed as methicillin-susceptible S. aureus (MSSA).

We evaluated the performances of three methods for detection of low-level methicillin resistance: the disk diffusion method using the cephamycin antibiotics cefoxitin and moxalactam, the Vitek 2 system (bioMerieux), and the MRSA-screen test (Denka). Detection of the mecA gene by PCR was considered to be the "gold standard." We also determined the sensitivity of the oxacillin disk diffusion method with 5- and 1-microg disks and that of the Oxascreen agar assay with 6 mg of oxacillin liter(-1) for detection of MRSA. We compared the distributions of MICs of oxacillin and cefoxitin by the E-test (AB Biodisk), and those of moxalactam by dilutions in agar, for MRSA and MSSA isolates.

The 152 clinical isolates of S. aureus studied were divided into 69 MSSA (mecA-negative) and 83 MRSA (mecA-positive) isolates, including 63 heterogeneous isolates and 26 class 1 isolates (low-level resistance). The cefoxitin and moxalactam disk diffusion tests detected 100% of all the MRSA classes: cefoxitin inhibition zone diameters were <27 mm, and moxalactam inhibition zone diameters were <24 mm. The Vitek 2 system and the MRSA-screen test detected 94 and 97.6% of all MRSA isolates, respectively. The sensitivities of the 5- and 1-microg oxacillin disks were 95.2 and 96.4%, respectively, whereas that of the Oxascreen agar screen assay was 94%. All of the tests except the 1-microg oxacillin disk test were 100% specific. For the class 1 MRSA isolates, the sensitivity of the Vitek 2 test was 92.3%, whereas those of the MRSA-screen test and the disk diffusion method with cefoxitin and moxalactam were 100%.

Therefore, the cefoxitin and moxalactam disk diffusion methods were the best-performing tests for routine detection of all classes of MRSA.

Practical Therapeutic Application of the Oxoid PBP2' Latex Agglutination Test for the Rapid Identification of Methicillin-Resistant Staphylococcus aureus in Blood Cultures

Elizabeth M. Marlowe, PhD
Andrea J. Linscott, PhD
Meganne Kanatani, PharmD
David A. Bruckner, ScD

Am J Clin Pathol 2002;118:287-291 Abstract quote

The Oxoid PBP2' latex agglutination test (OLA; Oxoid, Basingstoke, England) was evaluated in a controlled prospective study examining Staphylococcus aureus from 25 positive blood cultures.

Subcultures of positive blood cultures with coagulase-positive, gram-positive cocci in clusters were batched, and the OLA was performed at the end of the working day, once growth was seen on the plate. Results were sent to the infectious disease pharmacist for therapy evaluation, and the 24-hour minimum inhibitory concentration (MIC) was confirmed the next day. Blood culture OLA results correlated 100% with oxacillin MIC results for the patient, and results were available in as little as 3 hours after the blood culture was positive. The mean time difference between the OLA and MIC reports was 19.4 hours.

This test allowed same-day resistance marker reporting and was easily incorporated into the work flow of the clinical laboratory.

PCR

Rapid detection of methicillin-resistant staphylococci from blood culture bottles by using a multiplex PCR assay.

Louie L, Goodfellow J, Mathieu P, Glatt A, Louie M, Simor AE.

Sunnybrook and Women's College Health Sciences Centre. University of Toronto, Toronto, Ontario, Canada. St. Vincent Catholic Medical Centers, Brooklyn/Queens Region, Jamaica. New York Medical College, Valhalla, New York.
J Clin Microbiol 2002 Aug;40(8):2786-90 Abstract quote
Rapid detection and accurate identification of methicillin-resistant staphylococci are critical for the effective management of infections caused by these organisms.

We describe a multiplex PCR-based assay for the direct detection of methicillin-resistant staphylococci from blood culture bottles (BacT/Alert; Organon-Teknika, Durham, N.C.). A simple lysis method followed by a multiplex PCR assay designed to detect the nuc, mecA, and bacterial 16S rRNA genes was performed. A total of 306 blood culture specimens were collected over a period of 10 months from June 1998 to April 1999, consisting of 236 blood cultures growing staphylococci (including 124 methicillin-resistant Staphylococcus spp.), 50 positive blood cultures which grew organisms other than staphylococci, and 20 blood cultures that were negative for bacterial and fungal pathogens after 5 days of incubation and terminal subculture. DNA extraction, PCR, and detection could be completed in 2.5 h. Of the positive blood cultures with staphylococci, the multiplex PCR assay had a sensitivity and specificity of 99.2% and 100%, respectively.

Our results show that rapid, direct detection of methicillin-resistant staphylococci is possible, allowing clinicians to make prompt and effective decisions for the management of patients with staphylococcal bacteremia.

GROSS APPEARANCE/
CLINICAL VARIANTS CHARACTERIZATION

GENERAL

VARIANTS

ENDOCARDITIS

Staphylococcus aureus Endocarditis in Preterm Neonates.

Armstrong D, Battin MR, Knight D, Skinner J.

Departments of Neonatal Paediatrics and Paediatric Cardiology, University of Auckland, National Women's Hospital, Green Lane Hospital, Auckland, New Zealand.
Am J Perinatol 2002;19(5):247-52 Abstract quote
This article describes three extremely low birth weight infants with Staphylococcus aureus septicemia associated with insertion of a percutaneous central venous catheter who later developed endocarditis.

Echocardiography demonstrated large vegetations although only one infant had a murmur. Following a 6-week course of intravenous flucloxacillin and netilmicin, the endocarditis completely resolved and further intervention was unnecessary, although one baby died later as a result of volvulus and chronic lung disease.

Echocardiography should be performed to exclude invasive infection in infants with S. aureus septicemia even when there is no murmur or other evidence of endocarditis. If endocarditis is identified, a good outcome is possible with appropriate aggressive antibiotic therapy.

PEDIATRIC

Methicillin-resistant Staphylococcus aureus at children's hospitals in the United States.

Jarvis WR, Thornsberry C, Boyce J, Hughes JM
Pediatr Infect Dis 1985 Nov-Dec;4(6):651-5 Abstract quote
Although methicillin-resistant Staphylococcus aureus (MRSA) has emerged as an important pathogen in hospitalized adults in the United States, reports of MRSA in pediatric patients have been infrequent.

To determine the frequency at which MRSA is isolated from children, we surveyed the directors of microbiology at all acute care children's hospitals in the United States, and 57 of 67 (85%) laboratory directors responded to a mailed questionnaire. Those not testing S. aureus for methicillin susceptibility were excluded from the analysis. Of 53 (57%) laboratory directors 30 reported that MRSA had been isolated from patients in their hospitals. Between 1973 and 1981 the proportion of hospitals isolating MRSA increased significantly; 1 of 53 hospitals reported MRSA in 1973 compared to 20 of 53 hospitals in 1981 (P less than 0.001). Large hospitals (greater than or equal to 200 beds) reported MRSA isolates more frequently than did small hospitals (less than 200 beds) (P = 0.007). No association was found between the isolation of MRSA and the presence of burn or intensive care units, residency training programs or rotation of residents to other hospitals. MRSA isolation varied by standard metropolitan statistical area and geographic region.

These data show that the isolation of MRSA is increasing in frequency in pediatric patients and that the reporting of MRSA from children's hospitals varies by hospital size, standard metropolitan statistical area and region. Since MRSA causes significant morbidity and mortality, further studies are necessary to identify the risk factors for MRSA infections and to develop effective control measures

POST-OPERATIVE WOUND INFECTION

Methicillin-resistant Staphylococcus aureus as a causative agent of postoperative intra-abdominal infection: relation to nasal colonization.

Fierobe L, Decre D, Muller C, Lucet JC, Marmuse JP, Mantz J, Desmonts JM.

Department of Anesthesiology and Intensive Care, Bichat University Hospital, 75018 Paris, France.
Clin Infect Dis 1999 Nov;29(5):1231-8 Abstract quote
In the surgical intensive care unit of a university hospital, we investigated the frequency of and the risk factors for acquisition of methicillin-resistant Staphylococcus aureus (MRSA) during postoperative intra-abdominal infection (pIAI).

We conducted a prospective MRSA nasal screening and case evaluation for 17 months among 73 consecutive patients with having pIAI. MRSA pIAI was diagnosed when MRSA was obtained from culture of intraperitoneal fluids. The identity of nasal and peritoneal MRSA strains was assessed by genomic analysis. Twelve patients had MRSA pIAI, representing 21% of all MRSA infections acquired by the 73 patients. An organ system failure score of >/=1 and MRSA nasal carriage prior to pIAI were the independent risk factors for acquisition of MRSA pIAI.

Patients with MRSA pIAI had a longer intensive care unit stay and more reoperations than did those free of MRSA pIAI. We conclude that MRSA may be a causative pathogen in pIAI and may be related to nasal colonization.

PROGNOSIS AND TREATMENT CHARACTERIZATION

PROGNOSTIC FACTORS

RISK FACTORS FOR MRSA

Risk factors for developing clinical infection with methicillin-resistant Staphylococcus aureus (MRSA) amongst hospital patients initially only colonized with MRSA.

Coello R, Glynn JR, Gaspar C, Picazo JJ, Fereres J.

Servicio de Medicina Preventiva, Hospital Universitario San Carlos, Madrid, Spain.
J Hosp Infect 1997 Sep;37(1):39-46 Abstract quote
In hospital outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) many patients are initially colonized without infection. The reasons why some progress to infection while others do not are not known.

A cohort of 479 hospital patients, initially only colonized with MRSA, was followed prospectively for the development of MRSA infection. Risk factors for progression to infection were assessed using Cox proportional hazards survival analysis. Fifty-three patients (11.1%) developed 68 MRSA infections. Intensive care setting, administration of three or more antibiotics, ulcers, surgical wounds, nasogastric or endotracheal tubes, drains, and urinary or intravenous catheterization were all associated with increased rates of MRSA infection. Multivariate analysis showed that intensive care patients, compared with medical patients, had a higher rate of developing MRSA infection within the first four days of admission, with a hazard ratio of 26.9 (95% CI 5.7-126). Surgical wounds, pressure ulcers and intravenous catheterization were also independent risk factors, with hazard ratios (and 95% CI) of 2.9 (1.3-6.3); 3.0 (1.6-5.7) and 4.7 (1.4-15.6), respectively.

These findings suggest that, during an MRSA outbreak, clinical infection would be reduced if surgical and intensive care patients received priority for the prevention of initial colonization with MRSA. Prevention of pressure ulcers, and strict aseptic care of intravenous catheters and surgical wounds would also reduce the development of MRSA infection. Since early treatment with vancomycin is known to reduce the mortality, patients colonized with MRSA who also have one or more of these risk factors may warrant empirical vancomycin therapy at the earliest suggestion of infection.

TREATMENT

BACTEREMIA

Treatment and outcome of Staphylococcus aureus bacteremia: a prospective study of 278 cases.

Jensen AG, Wachmann CH, Espersen F, Scheibel J, Skinhoj P, Frimodt-Moller N.

Bldg 45, Sector for Microbiology, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark
Arch Intern Med 2002 Jan 14;162(1):25-32 Abstract quote
BACKGROUND: Staphylococcus aureus bacteremia is still a serious problem, and the optimal treatment is under debate. Only a few studies concerning treatment are available.

METHODS: The study population was all patients with a positive blood culture result for S aureus in Copenhagen County, Denmark, from May 1994 through April 1996. Of 278 patients with S aureus bacteremia, 186 were evaluated according to outcome in a prospective, observational follow-up study. The time above the minimum inhibitory concentration was estimated for dicloxacillin sodium for each treatment regimen and evaluated by logistic regression along with other potential risk factors.

RESULTS: The following variables were statistically associated with death: the presence of an uneradicated focus (odds ratio [OR], 6.7; 95% confidence interval [CI], 2.1-21.0); the presence of septic shock (OR, 3.7; 95% CI, 1.5-9.1); the total daily dose of penicillinase-stable penicillin less than 4 g (OR, 3.7; 95% CI, 1.3-11.1); and age 60 years or older (OR, 2.4; 95% CI, 1.1-5.3). The following variables were significantly associated with recurrence: the total daily dose of penicillinase-stable penicillin less than 3 g (OR, 3.9; 95% CI, 1.6-10.0) and the presence of a secondary focus (OR, 3.2; 95% CI, 1.3-7.7). Among 155 patients with observation time longer than duration of treatment, this factor (duration of treatment, <14 days) was significantly related to mortality (OR, 0.84; 95% CI, 0.76-0.94).

CONCLUSIONS: Focus eradication and the dosing of penicillinase-stable penicillin are important to the outcome of S aureus bacteremia. We recommend treatment with at least 1 g of penicillinase-stable penicillins 4 times daily for longer than 14 days.

MUPIROCIN NASAL OINTMENT

Intranasal mupirocin to prevent postoperative Staphylococcus aureus infections.
Perl TM, Cullen JJ, Wenzel RP, Zimmerman MB, Pfaller MA, Sheppard D, Twombley J, French PP, Herwaldt LA; The Mupirocin And The Risk Of Staphylococcus Aureus Study Team.

University of Iowa Colleges of Medicine and Public Health, Iowa City, USA.

N Engl J Med 2002 Jun 13;346(24):1871-7 Abstract quote
BACKGROUND: Patients with nasal carriage of Staphylococcus aureus have an increased risk of surgical-site infections caused by that organism. Treatment with mupirocin ointment can reduce the rate of nasal carriage and may prevent postoperative S. aureus infections.

METHODS: We conducted a randomized, double-blind, placebo-controlled trial to determine whether intranasal treatment with mupirocin reduces the rate of S. aureus infections at surgical sites and prevents other nosocomial infections.

RESULTS: Of 4030 enrolled patients who underwent general, gynecologic, neurologic, or cardiothoracic surgery, 3864 were included in the intention-to-treat analysis. Overall, 2.3 percent of mupirocin recipients and 2.4 percent of placebo recipients had S. aureus infections at surgical sites. Of the 891 patients (23.1 percent of the 3864 who completed the study) who had S. aureus in their anterior nares, 444 received mupirocin and 447 received placebo. Among the patients with nasal carriage of S. aureus, 4.0 percent of those who received mupirocin had nosocomial S. aureus infections, as compared with 7.7 percent of those who received placebo (odds ratio for infection, 0.49; 95 percent confidence interval, 0.25 to 0.92; P=0.02).

CONCLUSIONS: Prophylactic intranasal application of mupirocin did not significantly reduce the rate of S. aureus surgical-site infections overall, but it did significantly decrease the rate of all nosocomial S. aureus infections among the patients who were S. aureus carriers

Surgical site infections in orthopedic surgery: the effect of mupirocin nasal ointment in a double-blind, randomized, placebo-controlled study.

Kalmeijer MD, Coertjens H, Van Nieuwland-Bollen PM, Bogaers-Hofman D, De Baere GA, Stuurman A, Van Belkum A, Kluytmans JA.

Department of Pharmacy, Academic Medical Center, University of Amsterdam, 1100 DD Amsterdam, The Netherlands
Clin Infect Dis 2002 Aug 15;35(4):353-8 Abstract quote
The objective of this study was to determine whether use of mupirocin nasal ointment for perioperative eradication of Staphylococcus aureus nasal carriage is effective in preventing the development of surgical site infections (SSIs).

A randomized, double-blind, placebo-controlled design was used. Either mupirocin or placebo nasal ointment was applied twice daily to 614 assessable patients from the day of admission to the hospital until the day of surgery. A total of 315 and 299 patients were randomized to receive mupirocin and placebo, respectively. Eradication of nasal carriage was significantly more effective in the mupirocin group (eradication rate, 83.5% versus 27.8%). In the mupirocin group, the rate of endogenous S. aureus infections was 5 times lower than in the placebo group (0.3% and 1.7%, respectively; relative risk, 0.19; 95% confidence interval, 0.02-1.62).

Mupirocin nasal ointment did not reduce the SSI rate (by S. aureus) or the duration of hospital stay.

VANCOMYCIN

Increasing resistance to vancomycin and other glycopeptides in Staphylococcus aureus.

Tenover FC, Biddle JW, Lancaster MV.

Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA
Emerg Infect Dis 2001 Mar-Apr;7(2):327-32 Related Articles, Books, LinkOut

Increasing resistance to vancomycin and other glycopeptides in Staphylococcus aureus.

Tenover FC, Biddle JW, Lancaster MV.

Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. FTenover@cdc.gov

Strains of Staphylococcus aureus with reduced susceptibility to glycopeptides have been reported from Japan, the United States, Europe, and the Far East. Although isolates with homogeneous resistance to vancomycin (MICs = 8 microg/mL) continue to be rare, there are increasing reports of strains showing heteroresistance, often with vancomycin MICs in the 1-4 microg/mL range. Most isolates with reduced susceptibility to vancomycin appear to have developed from preexisting methicillin-resistant S. aureus infections. Many of the isolates with reduced susceptibility to glycopeptides have been associated with therapeutic failures with vancomycin. Although nosocomial spread of the vancomycin-intermediate S. aureus (VISA) strains has not been observed in U.S. hospitals, spread of VISA strains has apparently occurred in Japan. Broth microdilution tests held a full 24 hours are optimal for detecting resistance in the laboratory; however, methods for detecting heteroresistant strains are still in flux. Disk-diffusion tests, including the Stokes method, do not detect VISA strains. The Centers for Disease Control and Prevention and other groups have issued recommendations regarding appropriate infection control procedures for patients infected with these strains.

Staphylococcus aureus resistant to vancomycin--United States, 2002.
MMWR Morb Mortal Wkly Rep 2002 Jul 5;51(26):565-7 Abstract quote
Staphylococcus aureus is a cause of hospital- and community-acquired infections. In 1996, the first clinical isolate of S. aureus with reduced susceptibility to vancomycin was reported from Japan.

The vancomycin minimum inhibitory concentration (MIC) result reported for this isolate was in the intermediate range (vancomycin MIC=8 microg/mL) using interpretive criteria defined by the National Committee for Clinical Laboratory Standards. As of June 2002, eight patients with clinical infections caused by vancomycin-intermediate S. aureus (VISA) have been confirmed in the United States. This report describes the first documented case of infection caused by vancomycin-resistant S. aureus (VRSA) (vancomycin MIC > or = 32 microg/mL) in a patient in the United States.

The emergence of VRSA underscores the need for programs to prevent the spread of antimicrobial-resistant microorganisms and control the use of antimicrobial drugs in health-care settings.

Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Eight Edition. Mosby 1996.
Sternberg S. Diagnostic Surgical Pathology. Third Edition. Lipincott Williams and Wilkins 1999.
Weedon D. Weedon's Skin Pathology. Churchill Livingstone. 1997.
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Robbins Pathologic Basis of Disease. Sixth Edition. WB Saunders 1999.

Commonly Used Terms

Bacteria

Last Updated 8/19/2002

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LABORATORY/RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
RADIOLOGIC
LABORATORY MARKERS
GENERAL
Evaluation of Three Techniques for Detection of Low-Level Methicillin-Resistant Staphylococcus aureus (MRSA): a Disk Diffusion Method with Cefoxitin and Moxalactam, the Vitek 2 System, and the MRSA-Screen Latex Agglutination Test. Felten A, Grandry B, Lagrange PH, Casin I. Service de Bacteriologie-Virologie-Hygiene, Hopital Saint-Louis, 75475 Paris Cedex 10, France.	J Clin Microbiol 2002 Aug;40(8):2766-71 Abstract quote Very-low-level methicillin-resistant Staphylococcus aureus (MRSA), or class 1 MRSA, is often misdiagnosed as methicillin-susceptible S. aureus (MSSA). We evaluated the performances of three methods for detection of low-level methicillin resistance: the disk diffusion method using the cephamycin antibiotics cefoxitin and moxalactam, the Vitek 2 system (bioMerieux), and the MRSA-screen test (Denka). Detection of the mecA gene by PCR was considered to be the "gold standard." We also determined the sensitivity of the oxacillin disk diffusion method with 5- and 1-microg disks and that of the Oxascreen agar assay with 6 mg of oxacillin liter(-1) for detection of MRSA. We compared the distributions of MICs of oxacillin and cefoxitin by the E-test (AB Biodisk), and those of moxalactam by dilutions in agar, for MRSA and MSSA isolates. The 152 clinical isolates of S. aureus studied were divided into 69 MSSA (mecA-negative) and 83 MRSA (mecA-positive) isolates, including 63 heterogeneous isolates and 26 class 1 isolates (low-level resistance). The cefoxitin and moxalactam disk diffusion tests detected 100% of all the MRSA classes: cefoxitin inhibition zone diameters were <27 mm, and moxalactam inhibition zone diameters were <24 mm. The Vitek 2 system and the MRSA-screen test detected 94 and 97.6% of all MRSA isolates, respectively. The sensitivities of the 5- and 1-microg oxacillin disks were 95.2 and 96.4%, respectively, whereas that of the Oxascreen agar screen assay was 94%. All of the tests except the 1-microg oxacillin disk test were 100% specific. For the class 1 MRSA isolates, the sensitivity of the Vitek 2 test was 92.3%, whereas those of the MRSA-screen test and the disk diffusion method with cefoxitin and moxalactam were 100%. Therefore, the cefoxitin and moxalactam disk diffusion methods were the best-performing tests for routine detection of all classes of MRSA.
Practical Therapeutic Application of the Oxoid PBP2' Latex Agglutination Test for the Rapid Identification of Methicillin-Resistant Staphylococcus aureus in Blood Cultures Elizabeth M. Marlowe, PhD Andrea J. Linscott, PhD Meganne Kanatani, PharmD David A. Bruckner, ScD	Am J Clin Pathol 2002;118:287-291 Abstract quote The Oxoid PBP2' latex agglutination test (OLA; Oxoid, Basingstoke, England) was evaluated in a controlled prospective study examining Staphylococcus aureus from 25 positive blood cultures. Subcultures of positive blood cultures with coagulase-positive, gram-positive cocci in clusters were batched, and the OLA was performed at the end of the working day, once growth was seen on the plate. Results were sent to the infectious disease pharmacist for therapy evaluation, and the 24-hour minimum inhibitory concentration (MIC) was confirmed the next day. Blood culture OLA results correlated 100% with oxacillin MIC results for the patient, and results were available in as little as 3 hours after the blood culture was positive. The mean time difference between the OLA and MIC reports was 19.4 hours. This test allowed same-day resistance marker reporting and was easily incorporated into the work flow of the clinical laboratory.
PCR
Rapid detection of methicillin-resistant staphylococci from blood culture bottles by using a multiplex PCR assay. Louie L, Goodfellow J, Mathieu P, Glatt A, Louie M, Simor AE. Sunnybrook and Women's College Health Sciences Centre. University of Toronto, Toronto, Ontario, Canada. St. Vincent Catholic Medical Centers, Brooklyn/Queens Region, Jamaica. New York Medical College, Valhalla, New York.	J Clin Microbiol 2002 Aug;40(8):2786-90 Abstract quote Rapid detection and accurate identification of methicillin-resistant staphylococci are critical for the effective management of infections caused by these organisms. We describe a multiplex PCR-based assay for the direct detection of methicillin-resistant staphylococci from blood culture bottles (BacT/Alert; Organon-Teknika, Durham, N.C.). A simple lysis method followed by a multiplex PCR assay designed to detect the nuc, mecA, and bacterial 16S rRNA genes was performed. A total of 306 blood culture specimens were collected over a period of 10 months from June 1998 to April 1999, consisting of 236 blood cultures growing staphylococci (including 124 methicillin-resistant Staphylococcus spp.), 50 positive blood cultures which grew organisms other than staphylococci, and 20 blood cultures that were negative for bacterial and fungal pathogens after 5 days of incubation and terminal subculture. DNA extraction, PCR, and detection could be completed in 2.5 h. Of the positive blood cultures with staphylococci, the multiplex PCR assay had a sensitivity and specificity of 99.2% and 100%, respectively. Our results show that rapid, direct detection of methicillin-resistant staphylococci is possible, allowing clinicians to make prompt and effective decisions for the management of patients with staphylococcal bacteremia.

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
GENERAL
VARIANTS
ENDOCARDITIS
Staphylococcus aureus Endocarditis in Preterm Neonates. Armstrong D, Battin MR, Knight D, Skinner J. Departments of Neonatal Paediatrics and Paediatric Cardiology, University of Auckland, National Women's Hospital, Green Lane Hospital, Auckland, New Zealand.	Am J Perinatol 2002;19(5):247-52 Abstract quote This article describes three extremely low birth weight infants with Staphylococcus aureus septicemia associated with insertion of a percutaneous central venous catheter who later developed endocarditis. Echocardiography demonstrated large vegetations although only one infant had a murmur. Following a 6-week course of intravenous flucloxacillin and netilmicin, the endocarditis completely resolved and further intervention was unnecessary, although one baby died later as a result of volvulus and chronic lung disease. Echocardiography should be performed to exclude invasive infection in infants with S. aureus septicemia even when there is no murmur or other evidence of endocarditis. If endocarditis is identified, a good outcome is possible with appropriate aggressive antibiotic therapy.
PEDIATRIC
Methicillin-resistant Staphylococcus aureus at children's hospitals in the United States. Jarvis WR, Thornsberry C, Boyce J, Hughes JM	Pediatr Infect Dis 1985 Nov-Dec;4(6):651-5 Abstract quote Although methicillin-resistant Staphylococcus aureus (MRSA) has emerged as an important pathogen in hospitalized adults in the United States, reports of MRSA in pediatric patients have been infrequent. To determine the frequency at which MRSA is isolated from children, we surveyed the directors of microbiology at all acute care children's hospitals in the United States, and 57 of 67 (85%) laboratory directors responded to a mailed questionnaire. Those not testing S. aureus for methicillin susceptibility were excluded from the analysis. Of 53 (57%) laboratory directors 30 reported that MRSA had been isolated from patients in their hospitals. Between 1973 and 1981 the proportion of hospitals isolating MRSA increased significantly; 1 of 53 hospitals reported MRSA in 1973 compared to 20 of 53 hospitals in 1981 (P less than 0.001). Large hospitals (greater than or equal to 200 beds) reported MRSA isolates more frequently than did small hospitals (less than 200 beds) (P = 0.007). No association was found between the isolation of MRSA and the presence of burn or intensive care units, residency training programs or rotation of residents to other hospitals. MRSA isolation varied by standard metropolitan statistical area and geographic region. These data show that the isolation of MRSA is increasing in frequency in pediatric patients and that the reporting of MRSA from children's hospitals varies by hospital size, standard metropolitan statistical area and region. Since MRSA causes significant morbidity and mortality, further studies are necessary to identify the risk factors for MRSA infections and to develop effective control measures
POST-OPERATIVE WOUND INFECTION
Methicillin-resistant Staphylococcus aureus as a causative agent of postoperative intra-abdominal infection: relation to nasal colonization. Fierobe L, Decre D, Muller C, Lucet JC, Marmuse JP, Mantz J, Desmonts JM. Department of Anesthesiology and Intensive Care, Bichat University Hospital, 75018 Paris, France.	Clin Infect Dis 1999 Nov;29(5):1231-8 Abstract quote In the surgical intensive care unit of a university hospital, we investigated the frequency of and the risk factors for acquisition of methicillin-resistant Staphylococcus aureus (MRSA) during postoperative intra-abdominal infection (pIAI). We conducted a prospective MRSA nasal screening and case evaluation for 17 months among 73 consecutive patients with having pIAI. MRSA pIAI was diagnosed when MRSA was obtained from culture of intraperitoneal fluids. The identity of nasal and peritoneal MRSA strains was assessed by genomic analysis. Twelve patients had MRSA pIAI, representing 21% of all MRSA infections acquired by the 73 patients. An organ system failure score of >/=1 and MRSA nasal carriage prior to pIAI were the independent risk factors for acquisition of MRSA pIAI. Patients with MRSA pIAI had a longer intensive care unit stay and more reoperations than did those free of MRSA pIAI. We conclude that MRSA may be a causative pathogen in pIAI and may be related to nasal colonization.

PROGNOSIS AND TREATMENT	CHARACTERIZATION
PROGNOSTIC FACTORS
RISK FACTORS FOR MRSA
Risk factors for developing clinical infection with methicillin-resistant Staphylococcus aureus (MRSA) amongst hospital patients initially only colonized with MRSA. Coello R, Glynn JR, Gaspar C, Picazo JJ, Fereres J. Servicio de Medicina Preventiva, Hospital Universitario San Carlos, Madrid, Spain.	J Hosp Infect 1997 Sep;37(1):39-46 Abstract quote In hospital outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) many patients are initially colonized without infection. The reasons why some progress to infection while others do not are not known. A cohort of 479 hospital patients, initially only colonized with MRSA, was followed prospectively for the development of MRSA infection. Risk factors for progression to infection were assessed using Cox proportional hazards survival analysis. Fifty-three patients (11.1%) developed 68 MRSA infections. Intensive care setting, administration of three or more antibiotics, ulcers, surgical wounds, nasogastric or endotracheal tubes, drains, and urinary or intravenous catheterization were all associated with increased rates of MRSA infection. Multivariate analysis showed that intensive care patients, compared with medical patients, had a higher rate of developing MRSA infection within the first four days of admission, with a hazard ratio of 26.9 (95% CI 5.7-126). Surgical wounds, pressure ulcers and intravenous catheterization were also independent risk factors, with hazard ratios (and 95% CI) of 2.9 (1.3-6.3); 3.0 (1.6-5.7) and 4.7 (1.4-15.6), respectively. These findings suggest that, during an MRSA outbreak, clinical infection would be reduced if surgical and intensive care patients received priority for the prevention of initial colonization with MRSA. Prevention of pressure ulcers, and strict aseptic care of intravenous catheters and surgical wounds would also reduce the development of MRSA infection. Since early treatment with vancomycin is known to reduce the mortality, patients colonized with MRSA who also have one or more of these risk factors may warrant empirical vancomycin therapy at the earliest suggestion of infection.
TREATMENT
BACTEREMIA
Treatment and outcome of Staphylococcus aureus bacteremia: a prospective study of 278 cases. Jensen AG, Wachmann CH, Espersen F, Scheibel J, Skinhoj P, Frimodt-Moller N. Bldg 45, Sector for Microbiology, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark	Arch Intern Med 2002 Jan 14;162(1):25-32 Abstract quote BACKGROUND: Staphylococcus aureus bacteremia is still a serious problem, and the optimal treatment is under debate. Only a few studies concerning treatment are available. METHODS: The study population was all patients with a positive blood culture result for S aureus in Copenhagen County, Denmark, from May 1994 through April 1996. Of 278 patients with S aureus bacteremia, 186 were evaluated according to outcome in a prospective, observational follow-up study. The time above the minimum inhibitory concentration was estimated for dicloxacillin sodium for each treatment regimen and evaluated by logistic regression along with other potential risk factors. RESULTS: The following variables were statistically associated with death: the presence of an uneradicated focus (odds ratio [OR], 6.7; 95% confidence interval [CI], 2.1-21.0); the presence of septic shock (OR, 3.7; 95% CI, 1.5-9.1); the total daily dose of penicillinase-stable penicillin less than 4 g (OR, 3.7; 95% CI, 1.3-11.1); and age 60 years or older (OR, 2.4; 95% CI, 1.1-5.3). The following variables were significantly associated with recurrence: the total daily dose of penicillinase-stable penicillin less than 3 g (OR, 3.9; 95% CI, 1.6-10.0) and the presence of a secondary focus (OR, 3.2; 95% CI, 1.3-7.7). Among 155 patients with observation time longer than duration of treatment, this factor (duration of treatment, <14 days) was significantly related to mortality (OR, 0.84; 95% CI, 0.76-0.94). CONCLUSIONS: Focus eradication and the dosing of penicillinase-stable penicillin are important to the outcome of S aureus bacteremia. We recommend treatment with at least 1 g of penicillinase-stable penicillins 4 times daily for longer than 14 days.
MUPIROCIN NASAL OINTMENT
Intranasal mupirocin to prevent postoperative Staphylococcus aureus infections. Perl TM, Cullen JJ, Wenzel RP, Zimmerman MB, Pfaller MA, Sheppard D, Twombley J, French PP, Herwaldt LA; The Mupirocin And The Risk Of Staphylococcus Aureus Study Team. University of Iowa Colleges of Medicine and Public Health, Iowa City, USA.	N Engl J Med 2002 Jun 13;346(24):1871-7 Abstract quote BACKGROUND: Patients with nasal carriage of Staphylococcus aureus have an increased risk of surgical-site infections caused by that organism. Treatment with mupirocin ointment can reduce the rate of nasal carriage and may prevent postoperative S. aureus infections. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to determine whether intranasal treatment with mupirocin reduces the rate of S. aureus infections at surgical sites and prevents other nosocomial infections. RESULTS: Of 4030 enrolled patients who underwent general, gynecologic, neurologic, or cardiothoracic surgery, 3864 were included in the intention-to-treat analysis. Overall, 2.3 percent of mupirocin recipients and 2.4 percent of placebo recipients had S. aureus infections at surgical sites. Of the 891 patients (23.1 percent of the 3864 who completed the study) who had S. aureus in their anterior nares, 444 received mupirocin and 447 received placebo. Among the patients with nasal carriage of S. aureus, 4.0 percent of those who received mupirocin had nosocomial S. aureus infections, as compared with 7.7 percent of those who received placebo (odds ratio for infection, 0.49; 95 percent confidence interval, 0.25 to 0.92; P=0.02). CONCLUSIONS: Prophylactic intranasal application of mupirocin did not significantly reduce the rate of S. aureus surgical-site infections overall, but it did significantly decrease the rate of all nosocomial S. aureus infections among the patients who were S. aureus carriers
Surgical site infections in orthopedic surgery: the effect of mupirocin nasal ointment in a double-blind, randomized, placebo-controlled study. Kalmeijer MD, Coertjens H, Van Nieuwland-Bollen PM, Bogaers-Hofman D, De Baere GA, Stuurman A, Van Belkum A, Kluytmans JA. Department of Pharmacy, Academic Medical Center, University of Amsterdam, 1100 DD Amsterdam, The Netherlands	Clin Infect Dis 2002 Aug 15;35(4):353-8 Abstract quote The objective of this study was to determine whether use of mupirocin nasal ointment for perioperative eradication of Staphylococcus aureus nasal carriage is effective in preventing the development of surgical site infections (SSIs). A randomized, double-blind, placebo-controlled design was used. Either mupirocin or placebo nasal ointment was applied twice daily to 614 assessable patients from the day of admission to the hospital until the day of surgery. A total of 315 and 299 patients were randomized to receive mupirocin and placebo, respectively. Eradication of nasal carriage was significantly more effective in the mupirocin group (eradication rate, 83.5% versus 27.8%). In the mupirocin group, the rate of endogenous S. aureus infections was 5 times lower than in the placebo group (0.3% and 1.7%, respectively; relative risk, 0.19; 95% confidence interval, 0.02-1.62). Mupirocin nasal ointment did not reduce the SSI rate (by S. aureus) or the duration of hospital stay.
VANCOMYCIN
Increasing resistance to vancomycin and other glycopeptides in Staphylococcus aureus. Tenover FC, Biddle JW, Lancaster MV. Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA	Emerg Infect Dis 2001 Mar-Apr;7(2):327-32 Related Articles, Books, LinkOut Increasing resistance to vancomycin and other glycopeptides in Staphylococcus aureus. Tenover FC, Biddle JW, Lancaster MV. Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. FTenover@cdc.gov Strains of Staphylococcus aureus with reduced susceptibility to glycopeptides have been reported from Japan, the United States, Europe, and the Far East. Although isolates with homogeneous resistance to vancomycin (MICs = 8 microg/mL) continue to be rare, there are increasing reports of strains showing heteroresistance, often with vancomycin MICs in the 1-4 microg/mL range. Most isolates with reduced susceptibility to vancomycin appear to have developed from preexisting methicillin-resistant S. aureus infections. Many of the isolates with reduced susceptibility to glycopeptides have been associated with therapeutic failures with vancomycin. Although nosocomial spread of the vancomycin-intermediate S. aureus (VISA) strains has not been observed in U.S. hospitals, spread of VISA strains has apparently occurred in Japan. Broth microdilution tests held a full 24 hours are optimal for detecting resistance in the laboratory; however, methods for detecting heteroresistant strains are still in flux. Disk-diffusion tests, including the Stokes method, do not detect VISA strains. The Centers for Disease Control and Prevention and other groups have issued recommendations regarding appropriate infection control procedures for patients infected with these strains.
Staphylococcus aureus resistant to vancomycin--United States, 2002.	MMWR Morb Mortal Wkly Rep 2002 Jul 5;51(26):565-7 Abstract quote Staphylococcus aureus is a cause of hospital- and community-acquired infections. In 1996, the first clinical isolate of S. aureus with reduced susceptibility to vancomycin was reported from Japan. The vancomycin minimum inhibitory concentration (MIC) result reported for this isolate was in the intermediate range (vancomycin MIC=8 microg/mL) using interpretive criteria defined by the National Committee for Clinical Laboratory Standards. As of June 2002, eight patients with clinical infections caused by vancomycin-intermediate S. aureus (VISA) have been confirmed in the United States. This report describes the first documented case of infection caused by vancomycin-resistant S. aureus (VRSA) (vancomycin MIC > or = 32 microg/mL) in a patient in the United States. The emergence of VRSA underscores the need for programs to prevent the spread of antimicrobial-resistant microorganisms and control the use of antimicrobial drugs in health-care settings.

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