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Modern medicineLog in to save to my locker

Superbugs—unmasking the threat

March 01, 2003
By Alan R. Salkind MD, James M. Wooten PharmD

RN/DREXEL Home Study

Program
CE CENTER

Superbugs—unmasking the threat

CE credit is no longer available for this article. (Expired March 2005)

After reading it you should be able to:

1. Discuss options for controlling bacterial resistance.

2. Identify which bacteria have strains resistant to certain antibiotics.
3. Describe how bacteria develop resistance.

Originally posted March 2003

JAMES M. WOOTEN, PharmD, and ALAN R. SALKIND, MD

JAMES WOOTEN, a member of the RN editorial board, is an assistant professor at the University of Missouri-Kansas City School of
Medicine in Kansas City. ALAN SALKIND is an associate professor at the same institution.

KEY WORDS: methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate

Staphylococcus aureus (VISA), vancomycin-resistant Staphylococcus aureus (VRSA),
penicillin-resistant Streptococcus pneumococci (PRSP), multidrug-resistant Mycobacterium
tuberculosis (MDR-TB)

In many respects, antibiotic resistance is a bio-threat of our own making. This

backgrounder will help you understand how bacteria develop resistance, which
have strains resistant to certain antibiotics, and what options we have for
controlling them.

Jump to: Choose article section...  Go

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In the decades since antibiotics were first introduced, strains of bacteria that were once sensitive
to certain drugs developed or acquired mechanisms of resistance—thus rendering some of
medicine's best weapons ineffective against them.1,2 Consider, for instance, Streptococcus
pneumoniae. The Centers for Disease Control and Prevention (CDC) says that over the past five
years, S. pneumoniae's rate of resistance to penicillin has increased by more than 300%, and its
rate of resistance to cefotaxime sodium (Claforan) has increased by more than 1,000%.3 This
increase in antibiotic-resistant strains has led to a corresponding increase in morbidity and
mortality from infectious disease.4

Hospitals have had their share of battles with resistant organisms that are difficult to isolate and
treat. Resistant bacteria have also sprung up in the community, and common infections such as
otitis media, community-acquired pneumonias, urinary tract infections (UTIs), and tuberculosis
can all be caused by bacteria that are resistant to commonly used antibiotics.

Several factors have contributed to the spread of resistant bacteria. They include the overuse and
misuse of antibiotics in human and animal medicine and animal husbandry, global transmission
of resistant bacteria as the result of poverty and poor medical and infection control practices in
both developing countries and the United States, increased world travel, and increasing costs of
developing new antibiotics.5,6

To help combat antibiotic resistance and care for the patients it affects, nurses need first to
understand how bacteria develop resistance in the first place. It's also essential to know which
bacteria are problematic for which antibiotics, and the weapons—current and in
development—to which we can turn to address this problem.

How bacteria "learn" to defend themselves

To understand how resistant bacteria develop, it helps to review how existing antibiotics work.
Antibiotics are classified as either bacteriostatic (meaning they slow the growth of the bacteria to
allow the body's immune system to eliminate the bacteria) or bactericidal (they kill the target
organism). Although bactericidal agents are more efficient, bacteriostatic agents can also be
extremely beneficial, since they permit normal defenses of the host to destroy the bacteria.6

Antibiotics work by inhibiting specific processes that are essential for a bacterium's growth and
replication, including cell wall synthesis, normal cytoplasmic membrane structure and function,
or protein synthesis or ribosome function.6 Each antibiotic may have a unique way of
interrupting one or more of these processes, which makes certain antibiotics effective (or
ineffective) against certain bacteria.

A bacterium's resistance to antibiotics is either intrinsic or acquired. Intrinsic resistance to a

specific antibiotic is a result of the drug's inherent mechanism of action against a particular
bacterium. For example, gram-negative bacteria are intrinsically resistant to cloxacillin sodium
(Cloxapen, Cloxilean, others) and vancomycin HCl (Vancocin, Vancoled) because these bacteria
contain a protective outer membrane not found in gram-positive bacteria. This prevents the
antibiotic from reaching the target site.4

Acquired resistance results from a change in the bacteria's genetic composition that makes a
previously effective drug ineffective.4 The most important principle of acquired antibiotic

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resistance is natural selection—"survival of the fittest." Bacteria that develop a mutation that
protects them from the antibiotic are more likely to survive than those without the mutation.4 In
this way, the more susceptible ("weaker") organisms will die, leaving behind only those
organisms "strong" enough to resist the antibiotic.5 These resistant bacteria then pass on their
resistant genes to their offspring by replication. They can also transfer genetic information that
confers resistance to other bacteria by conjugation or transduction.6

In conjugation, plasmids—pieces of double-stranded DNA that occur outside the chromosomal

DNA—jump from one organism's genetic makeup to another.6 When they jump, they take with
them genetic codes for producing specific enzymes or products that make bacteria resistant. In
transduction, genetic information is transferred among bacteria by a virus that "picks up" pieces
of DNA that encode for resistance. Unlike conjugation, transduction makes it possible for
genetic information to be passed from one species of bacteria to another.

Four mechanisms of resistance

The mechanisms by which bacteria resist antibiotics reflect the mechanisms by which antibiotics
work. The four general mechanisms of resistance center around a bacterium's ability to inactivate
an antibiotic, reduce the intracellular concentration of the antibiotic, modify the target site of the
antibiotic, and eliminate the target site of the antibiotic.4

The most common mechanism of resistance is the production of enzymes that modify the
antibiotic, rendering it inactive.7 Resistance to penicillin results largely from the production by
bacteria of enzymes known as ß-lactamases.4 These enzymes hydrolyze the antibiotic's ß-lactam
ring, a structure essential for antibiotic activity. Another enzyme-induced mechanism of
resistance is production of acetyltransferases—which are known to inhibit aminoglycosides,
antibiotics that are effective against gram-negative bacteria.

Bacteria may reduce the intracellular concentration of the antibiotic by reducing the permeability
of its own outer membrane, by reducing uptake of the antibiotic across the cytoplasmic
membrane, or by pumping out the antibiotic across the cytoplasmic membrane, which is known
as active reflux.4 Active reflux is believed to play a role in resistance to many antibiotics,
including macrolides such as azithromycin (Zithromax), quinolones such as ciprofloxacin
(Cipro), ß-lactams such as penicillin, and chloramphenicol (Chloromycetin).4

Alteration in the target site of the antibiotic's action is another mechanism through which
bacteria become resistant.7 For example, ß-lactam antibiotics work by binding to penicillin-
binding proteins (PBPs), which play a role in the synthesis of the cell wall in a normal bacterial
cell. But, a bacterium with modified PBPs can be resistant to ß-lactams. Modification of PBPs is
a primary mode of penicillin resistance in S. pneumoniae, Neisseria meningitidis, and
Enterococcus faecium.4

Finally, some bacteria become resistant by eliminating the target site of antibiotic action
altogether. They acquire the ability to create new metabolic pathways that bypass the original
target site. This is the mechanism seen in strains of enterococci that have developed resistance to
glycopeptides such as vancomycin.4

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Certain bacteria can be problematic

Any type of bacteria has the potential to develop resistance to a previously effective antibiotic.
To treat an infection effectively, we need to know the resistance patterns of the particular
bacterium. If effective and safe alternative antibiotics are available, resistance may not be a
problem. Unfortunately, the development of new antibiotics has not kept pace with the
development of resistance among certain organisms.

For some resistant bacteria, treatment options are few—which puts patients at risk of being
infected with a strain of bacteria that can't be eliminated. If this strain is not contained, other
patients are at risk of being infected with the same organism, thus causing a potential epidemic.
Even when a resistant organism can be treated with alternative antibiotics, identifying the
resistance can take time, and in some cases, the infection may quickly become deadly before the
proper antibiotic treatment can be initiated.

Examples of bacterial infections that can be difficult to treat include Staphylococcus aureus,
enterococci, S. pneumoniae, Neisseria gonorrhoeae, and Mycobacterium tuberculosis.

Staphylococcus aureus. S. aureus is a cause of community-acquired and nosocomial infections,

and is the most common organism cultured from wound and soft-tissue infections.4 It's carried
on the skin by a large part of the population, usually in moist sites such as the nose, perineum,
and axillae, and can also survive for long periods on drier surfaces, including hands and medical
equipment.

More than 90% of S. aureus strains are resistant to penicillin.2 Methicillin-resistant S. aureus
(MRSA) has become a common pathogen, particularly in the long-term care setting.4

S. aureus is consistently susceptible only to glycopeptides, which include vancomycin and

teicoplanin (Targocid). Recently, however, vancomycin-intermediate S. aureus (VISA), which
has reduced susceptibility to vancomycin, and vancomycin-resistant S. aureus (VRSA) have
been documented.8

Stringent infection control procedures, including contact and isolation precautions and
handwashing, need to be implemented in healthcare facilities to limit the spread of MRSA.
Equally important, clinicians need to adhere to strict vancomycin utilization guidelines to ensure
that, like any antibiotic, the drug is prescribed only when necessary.

Enterococci. Enterococci are part of the normal human gut flora. They are usually not virulent
but can cause infection in patients whose resistance is impaired. If they reach normally sterile
sites in a compromised patient, enterococci can cause many types of clinical problems, including
wound infections and UTIs, each of which could potentially lead to septicemia.4 Serious
infections caused by resistant enterococci may be difficult to treat.

Enterococci are intrinsically resistant to quinolones like ciprofloxacin and to cephalosporins like
cefazolin (Ancef, Kefzol, others), and can readily develop resistance to other antibiotics. Most
enterococci isolated from hospital patients are now resistant to tetracyclines, macrolides,
chloramphenicol, and trimethoprim (Trimplex, Proloprim), which leaves vancomycin as the only
effective antibiotic available. Unfortunately, strains of vancomycin-resistant enterococci (VRE)

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have emerged, and many species of enterococci are now resistant to all established antibiotics.
VRE is a significant cause of morbidity and mortality among critically ill patients.9

Streptococcus pneumoniae. S. pneumoniae is a leading cause of illness and death in the United
States, and the biggest cause of potentially life-threatening, community-acquired diseases such
as pneumonia and meningitis.4 It's also the leading bacterial cause of otitis media.4

S. pneumoniae is of special concern among the very young and very old, two patient populations
with a high propensity for infection and in whom infections can be quite serious. S. pneumoniae
can be easily spread and is common in crowded areas like day care centers and nursing homes.

Since rapid, sensitive, and specific diagnostic tests are not available, the diagnosis of S.
pneumoniae infection is usually presumptive and the therapy usually empiric. Thus, antibiotics
are frequently prescribed for presumptive S. pneumoniae infection.

Until recently, all S. pneumoniae were susceptible to penicillin.7 Penicillin-resistant

Streptococcus pneumococci (PRSP)—which developed via alterations in one or more
PBPs—tend to become resistant to multiple antibiotics. ß-lactam-resistant pneumococci can also
be resistant to erythromycin, trimethoprim/sulfamethoxazole (Bactrim, Septra), and
tetracyclines, but are usually susceptible to vancomycin and imipenem/ cilastatin (Primaxin).

Options for treating PRSP include third-generation cephalosporins such as cefixime (Suprax),
clindamycin HCl (Cleocin), and some of the newer fluoroquinolones. (See the "Four generations
of fluoroquinolones" box.) In some areas of the United States, multiple resistant strains are
common, and there are few treatment options.

Neisseria gonorrhoeae. N. gonorrhoeae, the bacterium that causes gonorrhea, is a major cause
of pelvic inflammatory disease, ectopic pregnancy, and infertility; it can also facilitate
transmission of HIV.10 N. gonorrhoeae was at one time sensitive to a single IM dose of penicillin
G combined with oral probenecid (Benemid, Probalan). Now a significant percentage of
gonorrhea cases are resistant to penicillin G as well as other penicillins, such as ampicillin
(Omnipen, Polycillin, others) and amoxicillin (Amoxil, Biomox, others).

Current CDC treatment guidelines call for a single dose of ceftriaxone sodium injection
(Rocephin), cefixime, ciprofloxacin, or ofloxacin (Floxin) for uncomplicated gonorrhea.11
However, that may change with the increased incidence of this infection.

Mycobacterium tuberculosis. Tuberculosis (TB) remains one of the most common and
dangerous bacterial infections worldwide. Since the 1980s the number of cases reported in the
developed world has risen.

M. tuberculosis infections require treatment with combinations of three or four antibiotics for at
least six months. Treatment guidelines based on culture sensitivity reports should be followed
judiciously because inappropriate therapy (i.e., monotherapy) leads rapidly to resistance. Even
with combination therapy, resistance emerges when the dose isn't correct or the patient isn't
compliant.

Strains of multidrug-resistant M. tuberculosis (MDR-TB) are beginning to spread.12 These

resistant strains possess a certain gene that encodes for the ability to pump the various

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antitubercular agents out of the cell. Currently, since there are no effective alternative antibiotics
available, the prognosis for patients with drug-resistant TB is poor.12

Super drugs still needed for these superbugs

Although many inexpensive and effective antibiotics have been developed within the last
century, the rapid growth of antibiotic resistance has rendered many of these drug classes quite
ineffective against various bacteria. As a result, new antibiotics with unique mechanisms of
action are being investigated. These include three new classes of antibiotics—ketolides,
streptogramins, and oxazolidinones—as well as new drugs in the fluoroquinolone class.13

Ketolides. Ketolides currently being studied include telithromycin (Ketek), which a Food and
Drug Administration (FDA) Advisory Committee recommended for approval in January, and
one simply known as ABT773.13 These drugs are similar to macrolide
antibiotics—erythromycin, azithromycin, and clarithromycin (Biaxin)—but have structural
alterations that essentially establish them as a new class of antibiotic.

Ketolides have increased potency against many gram-positive bacteria, including those with
acquired resistance to macrolides. Like macrolides, ketolides inhibit protein synthesis within the
bacteria, but the nature and strength of their effect appears to be much stronger and much less
affected by factors that cause resistance to the macrolides.

This new class of agents has demonstrated a high level of activity against S. pneumoniae,
Streptococcus pyogenes, S. aureus, and Haemophilus influenzae, which makes them viable
alternatives for treating upper respiratory tract infections, sinusitis, and skin infections.
Telithromycin is the most extensively studied drug in this class; it has demonstrated excellent
clinical efficacy with once-daily dosing and appears to be well tolerated. Ketolides may be
especially useful in areas where macrolide resistance among S. pneumoniae is common.

Streptogramins. Quinupristin/ dalfopristin (Synercid), the first streptogramin, is a combination

of two antibiotics. Both agents are derived from the naturally occurring bacteria Streptomyces
pristinaspiralis and work by inhibiting protein synthesis. Alone, each agent is bacteriostatic, but
in combination they are bacteriocidal against gram-positive bacteria, including MRSA.

In 1999, quinupristin/dalfopristin was approved specifically for the treatment of bacteremia

caused by vancomycin-resistant E. faecium (VREF) and skin infections caused by MRSA or S.
pyogenes.14 The drug is not active against Enterococci faecalis, and differentiation of
enterococcal species is important to avoid misidentifying E. faecalis as E. faecium.14

Quinupristin/dalfopristin is for IV administration only. The usual adult dose is 7.5 mg/kg
(combined product) every eight to 12 hours.15 It is generally well tolerated, but may cause
frequent nausea, gastrointestinal discomfort, injection site pain, myalgias, and elevated liver
enzymes.

Oxazolidinones. Oxazolidinones are a synthetically derived class of antibiotics that appear to be

effective against specific resistant bacteria. They do not appear to share cross-resistance with
other antibiotic classes.

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Linezolid (Zyvox) is the first FDA-approved oxazolidinone.14 The drug appears to inhibit the
initiation of protein synthesis at the ribosomal level in susceptible bacteria. Linezolid is primarily
used for nosocomial infections caused by various gram-positive organisms with documented
resistance to other antibiotics.14

Linezolid can be administered both IV and orally every 12 hours, and must be used only when
indicated to avoid the development of resistance against it. Potential side effects include
thrombocytopenia, headache, nausea, and diarrhea.16 Other oxazolidinones are currently under
investigation.14

New fluoroquinolones. Fluoroquinolones, while not new, are a dynamic class in which many
new agents are being developed. All fluoroquinolones kill bacteria by disrupting bacterial
replication, transcription, and repair of bacterial DNA.17 Since the first one—ciprofloxacin—was
brought to market in 1987, fluoroquinolones have grown from being used primarily to treat
common bacteria causing UTIs to highly diverse agents for a wide variety of infections,
including those caused by resistant bacteria.

The newer fluoroquinolones are used to treat community-acquired pneumonia, upper respiratory
tract infections, and other infections caused by various gram-positive bacteria. The
fluoroquinolones currently approved by the FDA are categorized into four generations, each with
varying bacterial coverage. Compared with second-generation agents, the third- and fourth-
generation fluoroquinolones are only slightly less active against gram-negative pathogens, and
are significantly more active against gram-positive organisms, such as streptococci, atypical
pathogens, and, in some cases, anaerobes. Although many of the newer fluoroquinolones
demonstrate greater activity against staphylococci and enterococci, considerable resistance to
these agents has been noted, particularly in MRSA and E. faecium.

In addition to enhanced coverage, newer agents such as moxifloxacin HCl (Avelox) and
trovafloxacin mesylate (Trovan) are highly active against anaerobes.17 The newer agents offer a
much broader spectrum of action against gram-positive bacteria, but ciprofloxacin remains the
most effective fluoroquinolone against gram-negative pathogens, including Pseudomonas
aeruginosa. Sparfloxacin (Zagam) is unusual among the fluoroquinolones because it is not
highly active against P. aeruginosa.

The newer fluoroquinolones are generally well tolerated; however, because liver damage has
been attributed to its use, trovafloxacin should be used only in hospitalized patients, and not for
longer than 14 days.17

What we can do now to limit resistance

Although new antibiotics are effective at eradicating some organisms, the development of new
agents cannot keep up with the demand. Other approaches involve optimizing the use of existing
antibiotics by altering or combining existing drugs (see the "The antibiotic arsenal for resistant
bacteria" box), using antibiotics for shorter durations, or rotating antibiotics.4

Educating patients on proper antibiotic use is essential to containing resistance. Patient demand
contributes to the unnecessary use of antibiotics, which plays a major role in the spread of
resistance. It's estimated that physicians in the United States and Canada overprescribe

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antibiotics by 50%.5 In addition, many prescribers avoid narrow-spectrum drugs in favor of

broader-spectrum antibiotics that have wider applications—but this can lead to a broader range
of resistant bacteria. That eventually results in a smaller, more costly arsenal of antibiotics.6

Last year, the Centers for Disease Control and Prevention launched an educational antibiotic
resistance campaign aimed at clinicians that focused on four key strategies: preventing infection,
diagnosing and treating infection effectively, using antibiotics wisely, and preventing the
transmission of drug-resistant pathogens.18 The campaign outlines 12 specific steps, described in
the "A 12-step approach to preventing resistance" box, clinicians can take to prevent antibiotic
resistance in hospitalized adults.

The Alliance for the Prudent Use of Antibiotics (APUA, 617-636-0966) is a nonprofit
international organization dedicated to promoting and preserving the effectiveness of antibiotics.
To help reduce the spread of resistance, the APUA suggests that nurses and other clinicians
should educate patients on proper antibiotic use, not give in to patients' demands for unnecessary
antibiotics, prescribe (when possible) antibiotics that target only a narrow range of bacteria, use
isolation precautions for hospital patients with multidrug-resistant infections, become familiar
with local data on antibiotic resistance, and wash their hands thoroughly between patient visits.19

Because bacteria constantly evolve and can therefore develop resistance to any antibiotic, we
will always face the threat of superbugs. Preventive strategies and the development of newer
antibiotics will certainly help combat resistance. Ultimately, however, containing the spread of
resistant bacteria will depend upon our knowledge of the "enemy" and appropriate use of
antibiotics by prescribers, nurses, and patients alike.

REFERENCES
1. Stratton, C. (2001, December). New insights on the emergence of resistance in the community. Paper presented at
the 41st Interscience Conference on Antimicrobial Resistance 2001, Chicago.

2. Virk, A., & Steckelberg, J. (2000). Clinical aspects of antimicrobial resistance. Mayo Clin Proc, 75(2), 200.

3. Centers for Disease Control and Prevention. "Resistance and antibiotic use." 2002.
www.cdc.gov/drugresistance/community/files/ads/Resis&An.pdf (18 Dec. 2002).

4. American Pharmaceutical Association. "APhA special report: Combating antibiotic resistance." 2001.
www.pharmacist.com/pdf/combating _antibiotic_res_sr.pdf (18 Dec. 2002).

5. World Health Organization. "Overcoming antimicrobial resistance: World health report on infectious diseases
2000." 2000. www.who.int/infectious-disease-report/2000/ (18 Dec. 2002).

6. Williamson, J. S., & Wyandt, C. M. (2001). Microbial resistance: The plague of tomorrow. Drug Topics, 145(10),
55.

7. Yamashita, S. "Antibiotic resistance." Pharmacy Connects. 1999.

www.pharmacyconnects.com/content/phpractice/1999/06-99/ce-06-99.html (18 Dec. 2002).

8. Centers for Disease Control and Prevention. "Staphylococcus aureus resistant to vancomycin—United States,
2002." MMWR. 2002. www.cdc.gov/mmwr/PDF/wk/mm5126.pdf (18 Dec. 2002).

9. Patterson, J. E. (2001). Antibiotic utilization: Is there an effect on antimicrobial resistance? Chest, 119(Suppl 2),
426S.

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 Page 9 of 13

10. Centers for Disease Control and Prevention. "Increases in fluoroquinolone-resistant Neisseria
gonorrhoeae—Hawaii and California, 2001." MMWR. 2002.
www.cdc.gov/mmwr/preview/mmwrhtml/mm5146a1.htm (18 Dec. 2002).

11. Centers for Disease Control and Prevention. "Sexually transmitted disease treatment guidelines—2002."
MMWR. 2002. www.cdc.gov/mmwr/preview/mmwrhtml/rr5106a1.htm (16 Jan. 2003).

12 Alangaden, G. J., & Lerner, S. A. "Overview of antimicrobial resistance." 1997.

www.nfid.org/publications/clinicalupdates/id/antimicrobial.html (18 Dec. 2002).

13. Lomaestro, B. M. (2001, December). Promising new antimicrobials and antivirals. Paper presented at the 41st
Interscience Conference on Antimicrobial Resistance 2001, Chicago.

14. Young, M. G. (2000). New developments in antibiotics. Patient Care, 34(15), 73.

15. Aventis Pharmaceuticals. "Synercid prescribing information." 2000. www.synercid.com/pi_files/default.htm (18

Dec. 2002).

16. Pharmacia Corporation. "Zyvox prescribing information." 2002. www.pharmacia.com/products/pdf/Zyvox.pdf

(18 Dec. 2002).

17. King, D. E., Malone, R., & Lilley, S. H. (2000). New classification and update on the quinolone antibiotics. Am
Fam Physician, 61(9), 2741.

18. Centers for Disease Control and Prevention. "CDC promotes campaign to prevent antimicrobial resistance in
healthcare settings." 2002. www.cdc.gov/od/oc/media/pressrel/r020326.htm (18 Dec. 2002).

19. Alliance for the Prudent Use of Antibiotics. "Immediate actions you as a healthcare practitioner can take to help
limit antibiotic resistance." 2002. www.tufts.edu/med/apua/Practitioners/healthcare.html (18 Dec. 2002).

Four generations of fluoroquinolones

Fluoroquinolone antibiotics are broad-spectrum antibiotics that are particularly effective against
gram-negative organisms, especially Pseudomonas aeruginosa. They are effective in treating a
wide variety of infectious diseases, including those caused by bacteria that are resistant to other
antibiotics. Fluoroquinolones can be classified into four generations.

First generation

Nalidixic acid (NegGram)

Cinoxacin (Cinobac)

Second generation

Norfloxacin (Noroxin)
Lomefloxacin HCl (Maxaquin)
Enoxacin (Penetrex)
Ofloxacin (Floxin)
Ciprofloxacin (Cipro)

Third generation

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Levofloxacin (Levaquin)
Sparfloxacin (Zagam)
Gatifloxacin (Tequin)
Moxifloxacin HCl (Avelox)*

Fourth generation

Trovafloxacin mesylate (Trovan)

*Moxifloxacin is sometimes classified as a fourth-generation agent.

Source: King, D. E., Malone, R., & Lilley, S. H. (2000). New classification and update on the quinolone antibiotics.
Am Fam Physician, 61(9), 2741.

The antibiotic arsenal for resistant bacteria

As the prevalence of resistant strains of bacteria increases, clinicians must turn to new strategies,
such as combinations of existing antibiotics, and wait for researchers to develop new classes of
antibiotics with unique mechanisms of action. The chart below lists several bacteria that
commonly develop resistance, and the antibiotics—current and investigational—that may be
able to defeat them.

Resistant Type of
strains infection Suggested antibiotics
Methicillin- Recurrent Intranasal mupirocin (Bactroban
resistant infection calcium Nasal);
Staphylococcus trimethoprim/sulfamethoxazole
aureus (MRSA) (Bactrim, Septra) with or without
rifampin (Rifadin, Rimactane)
Under investigation: Topical
daptomycin
Life- Vancomycin HCl (Vancocin,
threatening Vancoled)
infections Potentially effective: Chloramphenicol
(Chloromycetin); minocycline
(Minocin); rifampin combinations;
trimethoprim/sulfamethoxazole
Under investigation: Newer
fluoroquinolones (see the "Four
generations of fluoroquinolones" box);
oxazolidinones;
quinupristin/dalfopristin (Synercid)
Linezolid (Zyvox);
quinupristin/dalfopristin

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Vancomycin- Life-
resistant S. threatening
aureus (VRSA) infections
Multidrug- Pneumonia Vancomycin; newer fluoroquinolones;
resistant telithromycin (Ketek)*
Streptococcus
pneumoniae Otitis media High-dose amoxicillin (Amoxil,
and sinusitis Biomox, others); amoxicillin/
clavulanate (Augmentin) for treatment
failures; ceftriaxone sodium
(Rocephin); clindamycin HCl
(Cleocin); telithromycin*
Meningitis Ceftriaxone or cefotaxime (Claforan)
except for highly resistant strains;
vancomycin in combination with
ceftriaxone or cefotaxime; meropenem
(Merrem)
Vancomycin- Urinary tract Linezolid; quinupristin/dalfopristin (for
resistant infections, E. faecium only); nitrofurantoin
Enterococci surgical site (Furadantin, Macrobid, others) if in
(VRE) infections, urine only
bacteremia

*Pending FDA approval

Source: American Pharmaceutical Association. "Combating antibiotic resistance." 2001.

www.pharmacist.com/pdf/combating_antibiotic_res_sr.pdf (13 Dec. 2002).

A 12-step approach to preventing resistance

Last year, the Centers for Disease Control and Prevention (CDC) launched a campaign to
explain what clinicians could do to prevent the spread of antibiotic resistance among hospitalized
adults. The following 12 steps are based on research and guidelines from the CDC and other
organizations.

Step 1: Vaccinate

Get influenza vaccine. Give influenza vaccine and pneumococcal vaccine to at-risk patients
before discharge.

Step 2: Get the catheters out

Use catheters only when essential. Use the correct catheter. Use proper insertion and catheter-
care protocols. Remove catheters when they are no longer essential.

Step 3: Target the pathogen

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Target empiric therapy to likely pathogens. Culture the patient. Target definitive therapy to
known pathogens. Optimize timing, regimen, dose, route, and duration. Monitor response and
adjust treatment when needed.

Step 4: Access the experts

Consult infectious disease experts for patients with serious infections.

Step 5: Practice antimicrobial control

Participate in local antimicrobial appropriate-use programs.

Step 6: Use local data

Know your antibiogram (data used to determine susceptibility of certain bacteria to specific
antibiotics). Know your formulary. Know your patient population.

Step 7: Treat infection, not contamination

Use proper antisepsis for blood cultures. Avoid culturing vascular catheter tips. Avoid culturing
through temporary vascular catheters.

Step 8: Treat infection, not colonization

Treat pneumonia, not the tracheal aspirate. Treat urinary tract infection, not the indwelling
catheter. Treat bacteremia, not the catheter tip or hub. Treat bone infection, not the skin flora.

Step 9: Know when to say "No" to vanco

Fever and an IV are not routinely an indication for vancomycin (Vancocin, Vancoled).
Methicillin-resistant Staphylococcus aureus (MRSA) may be sensitive to other antimicrobials.
Treat staphylococcal infection, not contaminants or colonization.

Step 10: Stop antimicrobial treatment

When infection is treated. When infection is not diagnosed. When infection is unlikely.

Step 11: Isolate the pathogen

Use standard infection control precautions. Contain infectious body fluids (follow airborne,
droplet, and contact precautions). When in doubt, consult infection control experts.

Step 12: Break the chain of contagion

Stay home when you are sick. Keep your hands clean.

Source: Centers for Disease Control and Prevention. "12 steps to prevent antimicrobial resistance among
hospitalized adults." 2002. www.cdc.gov/drugresistance/healthcare/ha/12steps_HA.htm (16 Dec. 2002).

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 Page 13 of 13

Emil Vernarec, ed. James Wooten, Alan Salkind. Superbugs--unmasking the threat. RN 2003;3:37.

Published in RN Magazine.

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