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MICROBIOLOGY

Ciprofloxacin has in vitro activity against a wide range of gram-negative and gram-positive microorganisms. The bactericidal action of ciprofloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, and recombination. The mechanism of action of fluoroquinolones, including ciprofloxacin, is different from that of penicillins, cephalosporins, aminoglycosides,
macrolides, and tetracyclines; therefore, microorganisms resistant to these classes of drugs may be susceptible to ciprofloxacin and other quinolones. There is no known cross-resistance between ciprofloxacin and other classes of antimicrobials. In vitro resistance to ciprofloxacin develops slowly by multiple step mutations.
Ciprofloxacin is slightly less active when tested at acidic pH. The inoculum size has little effect when tested in vitro. The minimal bactericidal concentration (MBC) generally does not exceed the minimal inhibitory concentration (MIC) by more than a factor of 2. Ciprofloxacin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section of the
package insert for CIPRO (ciprofloxacin hydrochloride) Tablets and CIPRO (ciprofloxacin*) 5% and 10% Oral Suspension.
Aerobic gram-positive microorganisms
Enterococcus faecalis (Many strains are only moderately susceptible.)
Staphylococcus aureus (methicillin-susceptible strains only)
Staphylococcus epidermidis (methicillin-susceptible strains only)
Staphylococcus saprophyticus
Streptococcus pneumoniae (penicillin-susceptible strains only)
Streptococcus pyogenes
Aerobic gram-negative microorganisms
Campylobacter jejuni Proteus mirabilis
Citrobacter diversus Proteus vulgaris
Citrobacter freundii Providencia rettgeri
Enterobacter cloacae Providencia stuartii
Escherichia coli Pseudomonas aeruginosa
Haemophilus influenzae Salmonella typhi
Haemophilus parainfluenzae Serratia marcescens
Klebsiella pneumoniae Shigella boydii Moraxella catarrhalis Shigella dysenteriae
Morganella morganii Shigella flexneri
Neisseria gonorrhoeae Shigella sonnei

Ciprofloxacin has been shown to be active against Bacillus anthracis both in vitro and by use of serum levels as a surrogate marker (see INDICATIONS AND USAGE and INHALATIONAL ANTHRAX – ADDITIONAL INFORMATION).
The following in vitro data are available, but their clinical significance is unknown.
Ciprofloxacin exhibits in vitro minimum inhibitory concentrations (MICs) of 1 µg/mL or less against most (= 90%) strains of the following microorganisms; however, the safety and effectiveness of ciprofloxacin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.
Aerobic gram-positive microorganisms
Staphylococcus haemolyticus
Staphylococcus hominis
Streptococcus pneumoniae (penicillin-resistant strains only)
Aerobic gram-negative microorganisms
Acinetobacter Iwoffi Pasteurella multocida
Aeromonas hydrophila Salmonella enteritidis
Edwardsiella tarda Vibrio cholerae
Enterobacter aerogenes Vibrio parahaemolyticus
Klebsiella oxytoca Vibrio vulnificus
Legionella pneumophila Yersinia enterocolitica
Most strains of Burkholderia cepacia and some strains of Stenotrophomonas maltophilia areresistant to ciprofloxacin as are most anaerobic bacteria, including Bacteroides fragilis and Clostridium difficile.

Susceptibility Tests
Dilution Techniques: Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized procedure. Standardized procedures are based on a dilution method1 (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of ciprofloxacin powder. The MIC values should be interpreted according to the following criteria:
For testing aerobic microorganisms other than Haemophilus influenzae, Haemophilus parainfluenzae, and Neisseria gonorrhoeaea:
MIC (µg/mL) Interpretation
=1 Susceptible (S)
2 Intermediate (I)
=4 Resistant (R)
These interpretive standards are applicable only to broth microdilution susceptibility tests with streptococci using cation-adjusted Mueller-Hinton broth with 2-5% lysed horse blood.
For testing Haemophilus influenzae and Haemophilus parainfluenzaeb:
MIC (µg/mL) Interpretation =1 Susceptible (S)
This interpretive standard is applicable only to broth microdilution susceptibility tests with Haemophilus influenzae and Haemophilus parainfluenzae using Haemophilus Test Medium1.
The current absence of data on resistant strains precludes defining any results other than “Susceptible”.
Strains yielding MIC results suggestive of a “nonsusceptible” category should be submitted to a reference laboratory for further testing.
For testing Neisseria gonorrhoeaec:
MIC (µg/mL) Interpretation
= 0.06 Susceptible (S)
0.12 – 0.5 Intermediate (I)
=1 Resistant (R)
This interpretive standard is applicable only to agar dilution test with GC agar base and 1% defined growth supplement.
A report of “Susceptible” indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of “Intermediate” indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high
dosage of drug can be used. This category also provides a buffer zone, which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected.
Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard ciprofloxacin powder should providethe following MIC values:
Organism MIC (µg/mL)
E. faecalis ATCC 29212 0.25 – 2.0
E. coli ATCC 25922 0.004 – 0.015
H. influenzaea ATCC 49247 0.004 – 0.03
N. gonorrhoeaeb ATCC 49226 0.001 – 0.008
P. aeruginosa ATCC 27853 0.25 – 1.0
S. aureus ATCC 29213 0.12 – 0.5
aThis quality control range is applicable to only H. influenzae ATCC 49247 tested by a broth microdilution procedure using Haemophilus Test Medium (HTM)1.
bThis quality control range is applicable to only N. gonorrhoeae ATCC 49226 tested by an agar dilution procedure using GC agar base and 1% defined growth supplement.
Diffusion Techniques: Quantitative methods that require measurement of zone diameters also providereproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure2 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 5-µg ciprofloxacin to test the susceptibility of microorganisms to ciprofloxacin.
Reports from the laboratory providing results of the standard single-disk susceptibility test with a 5-µg ciprofloxacin disk should be interpreted according to the following criteria:
For testing aerobic microorganisms other than Haemophilus influenzae, Haemophilus parainfluenzae, and Neisseria gonorrhoeaea:
Zone Diameter (mm) Interpretation
= 21 Susceptible (S)
16 – 20 Intermediate (I)
= 15 Resistant (R)
aThese zone diameter standards are applicable only to tests performed for streptococci using Mueller-Hinton agar supplemented with 5% sheep blood incubated in 5% CO2.
For testing Haemophilus influenzae and Haemophilus parainfluenzaeb:
Zone Diameter (mm) Interpretation
= 21 Susceptible (S)
bThis zone diameter standard is applicable only to tests with Haemophilus influenzae and Haemophilus parainfluenzae using Haemophilus Test Medium (HTM)2.
The current absence of data on resistant strains precludes defining any results other than “Susceptible”. Strains yielding zone diameter results suggestive of a “nonsusceptible” category should be submitted to a reference laboratory for further testing.
For testing Neisseria gonorrhoeaec:
Zone Diameter (mm) Interpretation
= 41 Susceptible (S)
28 – 40 Intermediate (I)
= 27 Resistant (R)
cThis zone diameter standard is applicable only to disk diffusion tests with GC agar base and 1% defined growth supplement. Interpretation should be as stated above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for ciprofloxacin. As with standardized dilution techniques, diffusion methods require the use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 5-µg ciprofloxacin disk should provide the following zone diameters in these laboratory test quality control strains:
Organism Zone Diameter (mm)
E. coli ATCC 25922 30 – 40
H. influenzaea ATCC 49247 34 – 42
N. gonorrhoeaeb ATCC 49226 48 – 58
P. aeruginosa ATCC 27853 25 – 33
S. aureus ATCC 25923 22 – 30

Despite the best attempts of the New York Times Wellness Blog to get me fired, I’m still here and doing fine. Somehow a post about how impressed I was with surgery, the professionals that practice it, and how many of my preconceptions about surgeons were incorrect, got all turned around into some “peak behind the curtain” into the secrets of the medical profession (Purchase Cheap Cipro ). This is terribly absurd and the article made a hash out of what I was trying to say. I was trying to relate some of the shock one experiences going from an academic setting into a clinical one for the first time, as a reminder to those who have done this before, and maybe preparation for those who have yet to make the jump. None of these things are secrets, and all could be culled from watching about 15 minutes of the Discovery channel or Scrubs. But the confusion of some individuals over what I was trying to communicate is still my problem, even if I was quoted all out of context. Clearly the biggest issue is the change in audience, my sb audience includes a lot of scientists and doctors, and the way I write is somewhat geared to this group (Purchase Cheap Cipro ). Thus you’ll notice in my comments mostly positive responses - especially from medical professionals like Orac, PalMD and various others. When the NYT expands my audience to a group of people who don’t know my writing, my assumptions or my more egregious stylistic shortcuts, it is not surprising there was some confusion and hurt feelings, not to mention some people with absolutely no sense of humor.

This does not mean that there is no problem however, ultimately this is a sign that I need to remember that I am writing in a public arena and need to be more careful with the assumptions I make about my audience on any given day. Rather than clamming up for the next couple (purchase cheap cipro )of decades until I’m tenured, instead I’m going to use this as an opportunity to broaden the appeal of the blog and help explain to a wider audience what evidence based medicine is, the process of learning it, and why I think medicine the best career in the world. Writing this way will help educate people about medicine and how its practiced, and at the same time improve my knowledge of medicine with the goal of making me a better doctor one day. So, back to basics.

First, an explanation of the role of a medical student in the arena of patient care. Medical students are being introduced into the profession of medicine. To accomplish this they take two years of some of the most arduous training imaginable, intensively learning about anatomy, physiology, pharmacology, biochemistry (if you purchase cheap cipro ), genetics, pathology, microbiology, physical exam, history taking, and all the other knowledge that makes up the foundation of clinical knowledge. By the third year, which is what I am currently in, you have accumulated more knowledge in two years than you probably have in your entire life. You are tested, retested, observed, corrected, and tested again and after all this work you get the incredible privilege of participating in patient care in your second two years of med school. This does not mean your first week of patient care is any less of a shock to the system - it is very much different from the purely academic pursuit of medicine - it is more of an apprenticeship in which you learn by doing and is certainly the most important part of learning to be a clinician. At this point you are participating in patient care, usually at an academic setting, and you see patients, take histories and physicals, learn how medical decisions are made in the care of individual patients, and in the case of surgery, observe how operations are performed. While you are an important part of the patient care team, you are not responsible for clinical decisions at this point and are at the bottom of the proverbial totem pole. You work with interns, residents and attendings who are ultimately responsible for medical decisions. For the most part, you observe, participate, tell them what you would do, and then wait patiently as these more experienced clinicians explain why you are right or wrong and what is the correct course of action. It is training to develop clinical judgement and competence in patient care. Further, when I say that I “scrub in” to a surgery, it means that I am allowed into the sterile field (purchase cheap cipro ,after scrubbing, gowning, gloving etc.) and am given the privilege of watching surgery up close. If you’re lucky you may get to participate, but in a very limited capacity, never beyond your abilities (purchase cheap cipro,usually just holding instruments, aiming a camera, applying traction, suction etc), always under the supervision of someone with between 5 and 40 years more experience than you, and in a very controlled environment. Always paramount is the patient’s well-being, and if it is ever in question you quickly find yourself shuffled back behind the doctors who are doing the very difficult and demanding work. Before you even step into the room one must remember the student has years of training to understand the pathology and anatomy of the case, the student has read up on the patients’ specific case, and has reviewed the surgical procedure, relevant pathology, anatomy etc. Before you work with patient on a medicine rotation you’ve done similar prep, and throughout the case are studying the patient’s case, lab results, textbooks of medicine, the scientific literature, etc., as part of your training. When you graduate from medical school and become an intern and then a resident you are still training for about 3-5 more years, you become directly responsible for patient care, and are under the supervision of an attending physician. This structure is ultimately very successful and academic medical centers provide the best medical treatment in the country, attract bright people, take all kinds of cases (the ones many other hospitals simply can’t handle,purchase cheap cipro), and constantly push the boundaries of medicine.

Now, onto the fun part. A clinical case. This is how we learn medicine, as being social animals, it’s almost always easier to remember medicine in the context of a person. You’ll always remember medical facts and treatments better if they are associated with an actual human being. And this is, of course, an artificial teaching case having nothing to do with an actual individual. I had a post all prepared describing a complicated procedure, but since we’re starting (get cheap discount drugs,purchase cheap cipro )from basics, let’s begin with wounds.

The patient is a 52 year old construction worker who suffered from an open fracture (bones sticking out of the skin) of his left radius and ulna (bones of the forearm) from on-the-job accident. He was taken to the ER, his arm was evaluated with a plain X-ray film, and the break was cleaned, reduced, and set in the OR. He received prophylactic cephalosporin antibiotics before the surgery. 24 hours later he is on your floor, admitted to your service, and he complains of chills, and severe burning pain at the site of his incision. The patient is alert and oriented to time (purchase cheap cipro ), place, and person, but is diaphoretic (sweating), pale and in some distress. He has a fever of 39.2, BP 140/90, and his heart rate 110 beats per minute. An examination of the arm reveals a brown, weeping wound at site of the repair, the arm is warm to the touch, and acutely painful. Physical exam and review of systems is otherwise unremarkable. Labs show an elevated white count. He has a history of type II diabetes and hypertension.