Contemporary Patterns of Antibiotic Resistance in Humans

*By Ron Jones, M.D.*

*Primary Investigator, SENTRY Program*

Antibiotic resistance in humans is growing around the world, but a
global collection of human and animal resistant strains shows little
significant association between animal and human patterns.

While antibiotic resistance is a public health threat around the world,
it is clear that hospital- and community-acquired diseases, unrelated to
animal drug use, constitute the major problems. Surveillance data
clearly show a disconnect between antibiotic resistance patterns in
humans and animals, calling into question the alleged link between
resistant bacteria in animals and those in humans. The data also affirm
that outbreaks of resistant bacteria are generally local, clearly
suggesting that management responses should be local, usually at the
ward or medical center level and dominantly attributed to
patient-to-patient dissemination or related to flawed infection control
practices.

The SENTRY Antimicrobial Surveillance Program, which since 1997 has
analyzed worldwide data from the collection of human and animal isolates
of bacterial strains, has documented the growing antibiotic resistance
problem around the world.^1^ The SENTRY Program also provides useful
data for evaluating the extent of current resistance threats among human
pathogens and any potential correlation or link between use of
antibiotics in animals, and the extent of emerging antibiotic resistance
in humans.

[Current Resistance Concerns in Human Practice]{.underline}. Of the over
two million hospital-acquired infections per year in the United States,
the resistant organisms of greatest risk for poor patient therapeutic
outcomes are:

1.  Methicillin-resistant staphylococci especially *S. aureus*;

2.  Enterococci resistant to vancomycin or "so-called VRE";

3.  *E. coli* and *Klebsiella* spp. resistant to "third-generation"
    cephalosporins;

4.  Most prevalent human clinical pathogens evolving toward resistance
    to ciprofloxacin and other fluoroquinolones; and

5.  Multi-drug resistance among *P. aeruginosa* and *Acinetobacter* spp.

Without exception, none of these problems are related to food-borne
pathogens or documented to have contributed [significant]{.underline}
risk to patients. Rates of resistance among monitored institutions vary
widely, but clear increases in resistance among the five (5) listed
nosocomial organism resistance problems are driven by use of
antimicrobials in humans and other factors that are headed by a decline
in the Public Health infrastructure and local infection control
practices.

Results from North America for the enterococci continue to see higher
resistance rates each year (17%, SENTRY Program for 2001), in an area
where no selecting agent exists in animal practice. Similarly,
Synercid-resistant strains continue to emerge in North America and
Europe, the latter where the animal product (virginamycin) was removed
from use, but pristinomycin remains utilized in human practice (decades
prior to Synercid release). Epidemic occurrences of vancomycin- and
Synercid-resistant strains continue to occur in Europe, North America
and now in Latin America driven by selective pressures of human
antibiotic treatment and breaks in infection control policies.

Among community-acquired infections, the principal concerns are:

1.  Penicillin and erythromycin resistances in *S. pneumoniae* and other
    streptococci;

2.  Methicillin resistance in staphylococcal skin infections;

3.  Fluoroquinolone and trimethoprim/sulfamethoxazole resistance in the
    Enterobacteriaceae causing urinary tract infections; and

4.  Resistance among food-borne pathogens, principally *Campylobacter*
    and *Salmonella*.

Results from the SENTRY Program indicate that invasive *Salmonella*
causes only 0.4% of all blood stream infections in the United States,
and the resistances to ampicillin (22%), ceftriaxone (1.6%),
ciprofloxacin (0.8%) and trimethoprim/sulfamethoxazole (6.3%) remain low
and unchanged over the last five years. Fluoroquinolone resistance in
*Campylobacter* was documented before and after its use in animal
health, but the preferred treatment (macrolides) remains completely
effective. Ironically, the susceptibility rates of these pathogens of
suspected animal reservoir origin have antibiotic resistance rates that
are significantly less than comparable Enterobacteriaceae of human
origin especially among pathogens associated with hospital-acquired
bacteremias or community-acquired urinary tract infections.

**North America**

The growing problem of antimicrobial resistance has led to renewed calls
to phase out or ban the use of certain antibiotics given to animals.
These calls have persisted despite the lack of sufficient evidence
demonstrating a significant risk to human health. Indeed, experts have
stated that banning antibiotics as growth promoters in animals will not
solve or even impact the problem of antibiotic resistance in
hospitals.^2^ A greater benefit could be achieved by restoring infection
control infrastructures and improving public health educational efforts
especially in food preparation.

**Most Serious Antimicrobial Resistance Problems**

**Facing Human Medicine in North America**

+----------------------------------+-----------------------------------+
| **GRAM-POSITIVE COCCI**          | **RISK FROM ANIMAL SOURCES**      |
+----------------------------------+-----------------------------------+
| ## **Staphylococci**             |                                   |
+----------------------------------+-----------------------------------+
| Methicillin or oxacillin         | None                              |
+----------------------------------+-----------------------------------+
| MLS~B~ (Synercid^®^)             | None                              |
+----------------------------------+-----------------------------------+
| Glycopeptides                    | None                              |
+----------------------------------+-----------------------------------+
| ## **Streptococci**              |                                   |
+----------------------------------+-----------------------------------+
| DRSP and other                   | None                              |
+----------------------------------+-----------------------------------+
| # **Enterococci**                |                                   |
+----------------------------------+-----------------------------------+
| Ampicillin and Aminoglycosides   | None                              |
+----------------------------------+-----------------------------------+
| Synercid^®^                      | None                              |
+----------------------------------+-----------------------------------+
| Glycopeptides                    | None                              |
+----------------------------------+-----------------------------------+
| Oxazolidinones                   | None                              |
+----------------------------------+-----------------------------------+

+----------------------------------+-----------------------------------+
| **GRAM-NEGATIVE BACILLI**        | **RISK FROM ANIMAL SOURCES**      |
+----------------------------------+-----------------------------------+
| Enterobacteriaceae *E coli,*     | None                              |
| Klebsiella spp., etc.            |                                   |
+----------------------------------+-----------------------------------+
| # ***Salmonella*                 |                                   |
|  and other food-borne species**  |                                   |
+----------------------------------+-----------------------------------+
| ESBLs                            | # None                            |
+----------------------------------+-----------------------------------+
| Stably derepressed Amp C (CMY-2, | Debated^a^                        |
| etc.)                            |                                   |
+----------------------------------+-----------------------------------+
| Fluoroquinolones                 | Debated^a^                        |
+----------------------------------+-----------------------------------+
| Novel β-lactamases               | # None                            |
+----------------------------------+-----------------------------------+
| #### **P. aeruginosa**           |                                   |
+----------------------------------+-----------------------------------+
| MDR isolates                     | None                              |
+----------------------------------+-----------------------------------+
| #### **Acinetobacters**          |                                   |
+----------------------------------+-----------------------------------+
| MD isolates                      | None                              |
+----------------------------------+-----------------------------------+
| #### **Campylobacters**          |                                   |
+----------------------------------+-----------------------------------+
| Macrolides                       | None                              |
+----------------------------------+-----------------------------------+
| Fluoroquinolones                 | Debated^b^                        |
+----------------------------------+-----------------------------------+

a\. Resistance rates in humans are higher than in animal strains.

b\. Drugs of therapeutic choice have remained active regardless of
resistance discovered in animal pathogens.

Recent reports from the Centers for Disease Control and Prevention
document a 23% decline in food-borne infections between 1999 - 2001.
This decrease was attributed to initiatives in slaughterhouse safety
practices, improved agricultural practices at the level of the farm,
adherence to new regulations governing fruit and other juices and an
expanded food safety education program. Clearly this indicates
significant progress on that small proportion of human infections that
are derived from animal sources.^3^

**References**

1.  Jones RN, Turnidge J. SENTRY Antimicrobial Surveillance Program.
    Five Year Summary \[Slide Presentation\].

2.  Acar J, Casewell M, Freeman J, Goossens H, Friis C. Avoparcin and
    virginiamycin as animal growth promoters: A plea for science in
    decision-making. Clinical Microbiology and Infections 2000;
    6(9):477-482.

3.  Cimons M, Food safety progress hailed while concerns remain. ASM
    News 68:317-318, 2002.