Infectious Diseases - Resistant Strains Of Bacteria

Antibiotics generally have been considered "miracle drugs" that control or cure many bacterial infectious diseases. However, during the last decade nearly all major bacterial infections in the world have become increasingly resistant to the most commonly prescribed antibiotic treatments, primarily because of repeated and improper uses of antibiotics. Decreasing inappropriate antibiotic use is the best way to control this resistance.

Bacteria such as pneumococcus, which causes pneumonia and children's ear infections—diseases long considered common and treatable—are evolving into strains that are proving to be untreatable with commonly used antibiotics. Pneumococcal bacteria cause many hundreds of thousands of cases of pneumonia, bacterial meningitis (inflammation of the tissue covering the brain and spinal cord), and almost half of the more than twenty-five million annual visits to American pediatricians for otitis media (middle ear infections). Since the 1980s, national rates of penicillin resistance have soared from less than 5% of patients treated to more than 30% of patients treated in 1996 (Jay C. Butler et al, "The Continued Emergence of Drug-Resistant Streptococcus Pneumoniae in the United States: An Update from the Centers for Disease Control and Prevention's Pneumococcal Sentinel Surveillance System," Journal of Infectious Diseases, vol. 174, no. 5, November 1996).

Investigators from the Department of Microbiology—a collaborative operation between Toronto Medical Laboratories and the Mount Sinai Hospital at the University of Toronto, Canada—made an even more alarming projection of pneumococcal resistance to penicillin in the United States from 2000 to 2004. The investigators developed a mathematical model that predicted that doubly resistant strains would increase from 8.6% in 1996 to an estimated 40.6% in 2004 (Allison McGeer and Donald E. Low, "Is Resistance Futile?" Nature Medicine, vol. 9, no. 4, April 2003, http://www.nature.com/nm/journal/v9/n4/full/nm0403-390.html).

To treat patients with penicillin-resistant pneumococcus infections, physicians use a combination of other antibiotics, such as vancomycin, imipenem, and rifampin for resistant pneumonia and clindamycin or cefuroxime for ear infections. One of the national health goals for 2010 is to achieve 90% coverage of noninstitutionalized adults age sixty-five and older for both influenza and pneumococcal vaccinations. In 2000 the U.S. Advisory Committee on Immunization Practices added adults age fifty to sixty-four to the universal recommendations for influenza vaccination. Many public health professionals are advocating widespread use of the pneumococcal vaccine in the hope that it will produce "herd immunity"—when a large proportion of the population is immune, the

TABLE 7.2 Reported cases of notifiable diseases, by month, 2003

TABLE 7.2
Reported cases of notifiable diseases, by month, 2003
Disease	Jan	Feb	Mar	Apr	May	Jun	Jul	Aug	Sep	Oct	Nov	Dec	Total
AIDSa	2,265	3,057	4,180	2,883	3,916	3,765	3,443	3,713	3,829	4,479	3,436	5,266	44,232
Botulism
Foodborne	1	—	3	1	1	1	1	—	1	2	1	8	20
Infant	6	8	6	4	6	1	7	7	6	5	12	8	76
Other (includes wound and unspecified)	—	1	4	1	2	2	6	—	5	5	1	6	33
Brucellosis	4	7	4	10	12	5	10	13	8	9	10	12	104
Chancroidb	1	12	1	3	9	3	7	1	7	6	2	2	54
Chlamydiab,c	54,988	67,590	85,499	68,695	83,561	67,315	61,388	83,633	67,459	70,657	84,924	81,769	877,478
Cholera	—	—	—	—	—	1	—	—	—	—	—	1	2
Coccidioidomycosisd	224	270	412	232	231	124	427	449	382	337	718	1,064	4,870
Cryptosporidiosis	126	120	204	146	199	188	276	563	634	397	352	301	3,506
Cyclosporiasis	4	3	3	4	5	11	15	12	1	3	5	9	75
Diphtheria	—	—	—	—	—	—	—	—	—	1	—	—	1
Ehrlichiosis
Human granulocytic	1	2	6	6	19	35	50	86	35	33	31	58	362
Human monocytic	6	3	3	—	16	25	51	46	44	27	33	67	321
Encephalitis/meningitis, arboviral
California serogroup	—	—	1	—	—	4	32	42	20	9	—	—	108
Eastern equine	—	—	—	—	1	—	7	4	1	—	—	1	14
St. Louis	—	—	—	—	1	1	6	24	7	1	1	—	41
West Nile	—	—	—	—	1	20	413	1,473	828	103	25	3	2,866
Enterohemorrhagic
Escherichia coli (EHEC)
EHECO157:H7	75	66	87	95	151	208	292	471	355	347	298	226	2,671
EHECnon-O157	8	11	20	13	21	11	25	54	14	27	25	23	252
EHEC not serogrouped	6	5	6	12	18	6	16	28	20	18	8	13	156
Giardiasis	1,045	1,159	1,498	1,179	1,538	1,268	1,466	2,526	2,055	1,908	2,066	2,001	19,709
Gonorrheab	22,468	26,193	30,600	23,984	30,889	25,401	24,559	33,339	27,283	27,211	32,362	30,815	335,104
Haemophilus influenzae, invasive, all ages/serotypes	119	142	187	159	215	151	159	164	126	124	147	320	2,013
Age < 5 yrs, serotype b	4	2	—	2	3	3	2	3	2	3	1	7	32
Age < 5 yrs, nonserotype b	5	10	16	11	15	11	6	10	6	5	5	17	117
Age < 5 yrs, unknown serotype	13	19	24	21	28	11	14	13	12	13	20	39	227
Hansen disease (leprosy)	6	2	16	4	6	5	11	8	9	1	7	20	95
Hantavirus pulmonary syndrome	2	2	—	1	6	3	—	3	1	—	3	5	26
Hemolytic uremic syndrome postdiarrheal	5	9	13	4	14	13	21	19	21	22	18	19	178
Hepatitis A, acute	405	504	624	505	590	505	485	637	753	709	1,233	703	7,653
Hepatitis B, acute	405	513	689	508	688	568	593	707	533	612	697	1,013	7,526
Hepatitis C, acute	66	75	123	70	97	76	84	79	82	78	119	153	1,102
Legionellosis	95	82	85	69	113	223	282	382	260	191	217	233	2,232
Listeriosis	34	41	40	36	54	59	67	106	58	73	45	83	696
Lyme disease	479	605	741	573	1,175	2,136	4,094	4,032	2,195	1,411	1,550	2,282	21,273
Malaria	68	88	95	74	71	96	135	188	161	126	124	176	1,402
Measles	1	3	3	11	7	6	6	11	3	—	1	4	56
Meningococcal disease	124	165	247	152	166	140	95	101	71	110	134	251	1,756
Mumps	14	15	32	13	23	19	12	20	18	11	24	30	231
Pertussis	436	448	701	530	695	660	685	1,108	964	1,102	1,729	2,589	11,647
Plague	—	—	—	—	—	1	—	—	—	—	—	—	1
Psittacosis	1	1	1	—	2	—	1	3	—	2	1	—	12
Q fever	4	4	1	12	10	11	4	7	1	2	4	11	71
Rabies
Animal	347	386	719	753	709	577	541	751	616	494	503	450	6,846
Human	—	—	—	—	—	—	—	1	1	—	—	—	2
Rocky Mountain spotted fever	19	13	30	31	49	96	87	167	162	92	124	221	1,091
Rubella	—	2	—	1	1	1	1	—	1	—	—	—	7
Congenital syndrome	—	1	—	—	—	—	—	—	—	—	—	—	1
Salmonellosis	1,782	1,950	2,446	2,178	3,278	3,736	5,061	6,345	4,883	4,252	4,008	3,738	43,657
SARS-CoVe	—	—	6	1	1	—	—	—	—	—	—	—	8
Shigellosis	1,502	1,406	1,881	1,397	2,813	2,231	1,927	2,386	2,015	1,790	2,118	2,115	23,581
Streptococcal disease, invasive, group A	356	645	853	650	660	458	357	339	221	222	441	670	5,872
Streptococcal Toxic-shock syndrome	14	16	27	19	19	17	5	6	6	6	6	20	161

TABLE 7.2 Reported cases of notifiable diseases, by month, 2003 [CONTINUED] "Table 1. Reported Cases of Notifiable Diseases, by Month—United States, 2003," in "Summary of Notifiable Disease—United States, 2003," Morbidity and Mortality Weekly Report, vol. 52, no. 54, April 22, 2005, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, http://www.cdc.gov/mmwr/PDF/wk/mm5254.pdf (accessed January 17, 2006)

TABLE 7.2
Reported cases of notifiable diseases, by month, 2003 [CONTINUED]
Disease	Jan	Feb	Mar	Apr	May	Jun	Jul	Aug	Sep	Oct	Nov	Dec	Total
Note: No cases of anthrax, Powassan encephalitis, western equine encephalitis, paralytic poliomyelitis, or yellow fever were reported in 2003.
aTotal number of acquired immunodeficiency syndrome (AIDS) cases reported to the Division of HIV/AIDS Prevention—Surveillance and Epidemiology, National Center for HIV, STD, and TB Prevention (NCHSTP), through December 31, 2003.
bTotals reported to the Division of Sexually Transmitted Diseases Prevention, NCHSTP, as of May 1, 2004.
cChlamydia refers to genital infections caused by Chlamydia trachomatis.
dNotifiable in <40 states.
eSevere acute respiratory syndrome—associated coronavirus; data reported to the Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, notifiable as of July 1, 2003.
fTotals reported to the Division of Tuberculosis Elimination, NCHSTP, as of April 1, 2004.
gDeath counts provided by Epidemiology and Surveillance Division, National Immunization Program.
SOURCE: "Table 1. Reported Cases of Notifiable Diseases, by Month—United States, 2003," in "Summary of Notifiable Disease—United States, 2003," Morbidity and Mortality Weekly Report, vol. 52, no. 54, April 22, 2005, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, http://www.cdc.gov/mmwr/PDF/wk/mm5254.pdf (accessed January 17, 2006)
Streptococcus pneumoniae, invasive
Drug-resistant	158	223	288	219	208	132	117	106	88	118	158	541	2,356
Age < 5 yrsd	61	79	78	68	72	71	41	33	34	54	94	160	845
Syphilis, total, all stagesb	2,261	2,622	3,737	2,831	3,355	2,612	2,585	3,159	2,455	2,550	3,030	3,073	34,270
Congenital (age < 1 yr)b	42	38	42	28	32	37	37	34	30	25	33	35	413
Primary and secondaryb	496	526	714	574	641	570	525	647	535	550	684	715	7,177
Tetanus	1	—	—	—	2	1	1	8	2	1	1	3	20
Toxic-shock syndrome	5	10	14	15	16	10	5	10	11	7	11	19	133
Trichinellosis	—	—	—	—	—	—	—	—	1	—	3	2	6
Tuberculosisf	593	912	1,021	1,284	1,214	1,296	1,216	1,197	1,202	1,385	1,057	2,497	14,874
Tularemia	2	1	1	—	5	15	15	13	13	9	5	50	129
Typhoid fever	14	26	38	23	24	25	34	51	51	22	24	24	356
Varicella	1,471	1,370	1,642	1,587	2,430	1,129	797	535	914	1,619	2,250	5,204	20,948
Varicella deathsg	—	—	—	—	—	—	—	—	—	1	1	—	2

likelihood of person-to-person spread is so small that the disease does not proliferate and even nonimmune individuals are protected from disease.

Increase in Escherichia Coli Infection Caused by Antibiotics

On July 25, 2002, a study funded by the National Institutes of Health (NIH) reported increasing rates of Escherichia coli (E. coli) infection attributable to antibiotic use among premature infants. The study, published in the New England Journal of Medicine (vol. 347, no. 4), examined the medical records of more than five thousand babies born throughout the United States and found that E. coli infection rates had more than doubled from three per one thousand births to seven per one thousand births. E. coli and group B streptococci are bacteria that frequently exist in the gastrointestinal tract and cause no medical problems. If, however, they are passed at birth from a pregnant mother to her unborn child, then the infant's immune system may be unable to effectively combat the infection.

The study found that rates of group B strep infection among infants decreased by almost 75% during the 1990s, probably in response to increasing use of antibiotics during labor and delivery (the birthing process) to prevent mother-to-infant spread of the infection. The antibiotic most often used was amoxicillin, an antibiotic that combats strep but does not harm E. coli. As a direct result of the effort to reduce strep infections, E. coli infections increased. The researchers observed that E. coli had surpassed group B strep as the most commonly occurring infection among premature infants. This finding is considered troubling because E. coli infection is potentially more dangerous than strep infection.

Addressing the prevalence of infection attributable to antibiotic use, an April 2006 report from the National Institute of Allergy and Infectious Diseases (NIAID is one of the National Institutes of Health) asserted that antimicrobial resistance is driving up health care costs, increasing the severity of disease, and increasing mortality rates from selected infections. The institute found that more than 70% of the bacteria that cause hospital-acquired infections were resistant to at least one of the antibiotics most frequently used to treat them. Patients infected with antibiotic-resistant organisms were more likely to have longer hospital lengths of stay and require treatment with medications that were less effective, more toxic, and more costly ("The Problem of Antimicrobial Resistance," National Institute of Allergy and Infectious Diseases, http://www.niaid.nih.gov/factsheets/antimicro.htm).

Educating Physicians and Patients about Appropriate Use of Antibiotics

According to the CDC, antibiotic resistance is among the most urgent public health problems in the world. In 1995 the CDC Division of Bacterial and Mycotic Diseases began a national campaign to reduce antimicrobial resistance by encouraging appropriate use of antibiotics. In 1999 the CDC worked with several medical professional societies to develop educational programs for medical students, physicians, and patients. In a published statement, Dr. Richard Besser, medical director of the CDC's National Campaign for Appropriate Antibiotic Use, called for physician and public support to tackle the problem. Dr. Besser asserted:

The biggest problem is inappropriate prescribing of antibiotics. Up to 40% of antibiotics prescribed in physicians' offices are for viral infections, which are not treatable with antibiotics. There are many reasons for this, including demand from patients, time pressures on physicians, and diagnostic uncertainty. Patients want to get back to work or get their children back to school, and physicians want their patients to feel satisfied with treatment. The result is over-prescribing of antibiotics, resulting in the development of resistant bacteria. The best way to combat this practice is to educate physicians and the public to decrease both demand and over-prescribing. In addition, providing clinicians with better means of diagnosing respiratory infections may remove some of the uncertainty that promotes over-prescribing.

In February 2004 the CDC reported that pressure from parents makes a difference in the pediatrician's prescribing method. One study funded by a grant from the Robert Wood Johnson Foundation showed that doctors prescribe antibiotics 65% of the time if they feel that parents expect them, but only 12% of the time if they feel parents do not expect them (Rita Mangione-Smith et al., Presentation of UCLA Study at the May 6, 2002, Pediatric Academic Societies, Baltimore, MD). A study published in the October 2005 issue of the Journal of the American Academy of Nurse Practitioners found that nurse practitioners and physicians continue to prescribe inappropriate antibiotics to patients with viral upper-respiratory tract infections, a practice that may lead to increased rates of antimicrobial resistance. The researchers also found that highly marketed broad-spectrum antibiotics are being prescribed excessively to patients with diagnoses of viral illnesses despite the fact that it is well accepted that antibiotics offer no benefit in the treatment of these illnesses.

Reducing antibiotic use lowers rates of drug-resistant bacteria. Investigators in France tested two methods intended to reduce the rate of penicillin-resistant pneumococci present in kindergarten students (Didier Guillemot, Emmanuelle Varon, Claire Bernède, Philippe Weber, Laurence Henriet, Sylvie Simon, Cécile Laurent, Hervé Lecoeur, and Claude Carbon, "Reduction of Antibiotic Use in the Community Reduces the Rate of Colonization with Penicillin GNonsusceptible Streptococcus pneumo-niae," Clinical Infectious Diseases, vol. 41, no. 7, October 1, 2005). The first prescription-reduction method involved not prescribing antibiotics for respiratory tract infections that were thought to be viral, since antibiotics work against bacteria, not viruses. The second approach, a dose/duration method, entailed using only recommended doses of antibiotics for no longer than five days. The researchers also targeted physicians, pharmacists, parents, and children in the groups receiving both types of treatment with an information campaign about antibiotic resistance and appropriate antibiotic use. A control group of children and their doctors received no specific information about antibiotic use.

At the conclusion of the study, antibiotic use had declined by more than 15% in both treatment groups, compared with less than 4% in the control group. While colonization by regular pneumococci was higher in the treatment groups than in the control group, colonization by penicillin-resistant pneumococci was lower in the treatment groups than in the control group. The prescription-reduction group saw the greatest decline in penicillin-resistant colonization—from 53% to 35%—and the dose/duration group dropped from 55% to 44%. The control group remained virtually unchanged. This indicates that reduced antibiotic use permits drug-susceptible bacteria to re-establish themselves as dominant colonizers of the respiratory tract. The investigators concluded that reducing the number of prescriptions and the dose and duration of needed antibiotics has the potential to generate significant and rapid reductions of penicillin-resistant pneumococcal colonization in areas that have high rates of drug-resistant bacteria.

These findings highlight the need for professional and public awareness and understanding of the need to assume active roles in preventing antibiotic resistance. Consequences of failure of antibiotics to treat formerly treatable illnesses could be dire: longer-lasting illnesses, more physician office visits or longer hospital stays, the need for more expensive and toxic medications, and even death.