Breastfeeding while on antibiotics

If, however, a clear response is not observed and the organism is resistant, therapy should be changed in accordance with susceptibility testing results.

The optimal duration of therapy for pneumococcal pneumonia is uncertain. Pneumococci are not readily detected in sputum microscopically by culture more than 24 hours after the administration of an effective antibiotic.

Experience obtained early in the antibiotic era showed that 5 to 7 days of therapy sufficed, and a small-scale study in the 1950s showed that a single dose of procaine penicillin, which maintains an effective antimicrobial level for as long as 24 hours, could cure otherwise healthy young adults of pneumococcal pneumonia. Nevertheless, the tendency of the medical profession has been to prolong therapy and, in the absence of data to prove additional benefit, most physicians now treat pneumonia for 10 to 14 days. Three to 5 days of close observation with parenteral therapy for pneumococcal pneumonia and a final few days of oral treatment, in all not exceeding 5 days after the patient has become afebrile (temperature o F), may be the best approach.The overall duration of therapy should not exceed 10 days. Failure of the patient to defervesce within 3 to 5 days should stimulate a review of the organism’s antibiotic susceptibility, as well as a search for a loculated infection such as empyema. Pneumococcal meningitis has been treated with 12 to 24 million units of penicillin every 24 hours, 2g ceftriaxone every 12 hours or 2mg cefotaxime every 6 hours.

Any of these regimens are effective against antibiotic-susceptible S. pneumoniae and may be effective against intermediately resistant ones; pharmacokinetic considerations and achievable cerebrospinal fluid (CSF) levels favor the use of ceftriaxone.

During treatment of resistant strains, beta-lactam antibiotics are likely not to achieve therapeutic levels in CSF. This explains why, until susceptibility results are reported, vancomycin is recommended along with a beta-lactam.

In patients who have major penicillin and cephalosporin allergies, vancomycin and/or imipenem can be used; 1 to 2% of patients who have had life-threatening reactions to cephalosporins have an adverse reaction to a carbapenem.

Unless the history suggests a life-threatening reaction to a beta-lactam, ceftriaxone or cefotaxime are preferred.

In treating pneumococcal meningitis, addition of dexamethasone, 10mg four times daily, leads to a distinctly better outcome.

Because of the possibility that steroids may diminish the penetration of antibiotics into the central nervous system (CNS), patients receiving these agents should be observed particularly closely; repeat spinal taps may be needed to document abatement of CSF abnormalities, particularly if there is any suggestion of a delayed clinical response. In any case, steroid administration should not be continued beyond the recommended 4 days. Pneumococcal endocarditis is associated with rapid destruction of heart valves, and all patients with this disease should be evaluated from the start by a cardiologist and/or a cardiovascular surgeon. Initial therapy should include vancomycin and ceftriaxone until the results of minimal bactericidal concentration testing are known. An aminoglycoside may inhibit the bactericidal activity of beta-lactam antibiotics and should not be added unless synergy in vitro is documented to occur. Corticosteroids, statins, and macrolides all exhibit a variety of anti-inflammatory effects.

The use of steroids in treating meningitis has been discussed earlier in this chapter. Randomized prospective studies have, in fact, shown no benefit from the addition of corticosteroids in treating pneumonia, but a large prospective study is currently underway within the US Veterans Affairs health care system.

Patients who are already on treatment with a statin at the time of admission for pneumococcal pneumonia have better outcomes than those who are not; a prospective study in which patients are randomized to receive a statin has not been reported.

Several case control studies have compared outcomes in patients receiving a macrolide and a beta-lactam with those in patients receiving a macrolide alone.

Results have favored the former group but, once again, a prospective study has not been done. The subject of pneumococcal resistance to antibiotics is complicated because definitions have changed and susceptibility patterns have evolved, but these definitions will dictate good clinical practice, and clinicians need to understand them. In 2008, after two decades of increasing emphasis on the prevalence of penicillin-resistant pneumococci, the definitions of susceptibility were changed to reflect the site of infection and the route of therapy.

For infections other than those involving the CNS that are treated with parenteral penicillin, susceptibility, intermediate resistance and resistance to penicillin are now defined as mean inhibitory concentration (MIC) less than 2?g/mL, 4?g/mL, and greater than or equal to 8?g/mL, respectively.

If oral penicillin is to be used for therapy, the old definitions apply, such that organisms with MIC less than 0.06?g/mL are called susceptible, those with a MIC of 0.1 to 1.0?g/mL have intermediate resistance and isolates with MIC greater than or equal to 2?g/mL are called resistant, reflecting the substantially lower tissue levels achievable with that therapy. In CNS infection, organisms with MIC less than or equal to 0.06?g/mL are susceptible; those with MIC greater than or equal to 0.12?g/mL are regarded as resistant.

Similar approaches have been developed to define susceptibility to amoxicillin, ceftriaxone, and other beta-lactam antibiotics. For example, MICs for susceptibility, intermediate resistance, and resistance to amoxicillin are defined simply as less than or equal to 2?g/mL, 4?g/mL, and greater than or equal to 8?g/mL, respectively, reflecting the concept that no physician would use oral therapy to treat a CNS infection.

For ceftriaxone, there are separate definitions for CNS and non-CNS infections. By these definitions, at the present time in the United States: 65% of isolates appear to be susceptible to levels achieved with oral penicillin; 17% are intermediately resistant, and 17% are resistant.

93% of all pneumococci are susceptible to penicillin if given parenterally or amoxicillin if given orally; 5% are intermediate, and 2% are resistant. In cases of meningitis, 65% of organisms are susceptible to penicillin and 35% are resistant (no intermediate resistance is defined). For ceftriaxone, in non-CNS infections, 94% of organisms are susceptible, 5% are intermediate and 1% are resistant; in CNS infections, these percentages are 88%, 7%, and 5%, respectively. Pneumococci with low MICs for penicillin remain susceptible to most other antibiotics, whereas strains that have reduced susceptibility to penicillin tend to be multiply resistant. At present, in the United States: approximately 20% of all pneumococci are resistant to macrolides.

30% are resistant to trimethoprim/sulfamethoxazole.

In general, greater than 98% of isolates remain susceptible to fluoroquinolones, probably because these drugs are not used to treat children.

nearly all pneumococci remain susceptible to ceftaroline, vancomycin, linezolid, or tigecycline.

How do patients contract this infection, and how do I prevent spread to other patients?

pneumoniae is largely confined to humans, generally to the respiratory tract, and is spread from person to person by intimate contact or by aerosol. A single nasopharyngeal swab yields pneumococci in 5 to 10% of healthy adults and 20 to 40% of healthy children.

The percentage increases to 40 to 60% or greater in toddlers and young children in daycare, and is even greater among all children in more primitive societies. The numbers of organisms present in the nasopharynx of infants and young children is much greater than in adults, a fact that explains the high false-positive rate for the pneumococcal urine antigen test (and its lack of utility) in those populations (see later in this chapter, laboratory diagnosis). In adults, close, crowded living conditions such as occur in military camps, prisons, shelters for the homeless, and nursing homes are associated with epidemics, but contact in schools or in the workplace is generally not.

The common feature for outbreaks is that, in addition to crowding and close contact, the population has some additional feature(s) that contribute(s) to susceptibility to infection, often a concurrent outbreak of a viral respiratory infection and/or physical or emotional stress. Pneumococcal colonization stimulates production of anticapsular antibody. In infants and young children, otitis media follows acquisition of a new colonizing strain. After a few weeks, protection reflects the presence of antibody. An important clinical corollary of

this

Before the widespread use of conjugate pneumococcal vaccine (see later in this chapter, prevention) in infants and toddlers, the incidence of invasive pneumococcal disease was: 100 cases per 100,000 population of infants.

100 cases per 100,000 population of persons aged greater than or equal to 70 years.

In the past few years, thanks to that vaccine, the incidence in these groups is 25, 8, and 60, respectively.

In certain populations, including African-Americans, Native Americans (particularly Alaskans) and certain aboriginal populations, the incidence may be up to 10-fold greater, although it is unclear to what extent genetic or environmental factors are responsible.

Infection control issues: Since several steps intervene between exposure to an organism, colonization, and development of infection, direct contagion is not generally an issue. Spread of pneumococcal infection within a hospital environment is exceedingly rare. There are no recommendations beyond universal precautions.

Two kinds of pneumococcal vaccine are currently available.

Pneumococcal capsular polysaccharide vaccine, marketed as Pneumovax®, contains 25?g of capsular polysaccharides from each of 23 common infecting serotypes of S.

Protein-conjugate pneumococcal vaccine contains capsular material from 13 pneumococcal serotypes, Prevnar13® (PCV13). The capsular polysaccharides are each bound chemically to a nontoxigenic protein that closely resembles diphtheria toxin. Many studies and meta-analyses, based largely on case control studies, have shown approximately 60 to 70% protection against invasive pneumococcal disease and slightly lower protection against nonbacteremic pneumococcal pneumonia.

The problem with pneumococcal vaccination is that those who are in greatest need of it are least likely to generate good antibody responses. Older persons and those who have chronic lung or heart disease have lower antibody levels after vaccination, and their immunoglobulin (Ig) G is less active in functional assays in vitro. Persons who have immunosuppressive conditions that place them at highest risk of pneumococcal infection, such as multiple myeloma, Hodgkin disease, splenectomy, lymphoma, nephrotic syndrome, renal failure, cirrhosis, sickle cell disease, bone marrow transplantation, and human immunodeficiency virus (HIV) infection respond poorly, if at all, to polysaccharide antigens.

Persons who have recovered from pneumococcal pneumonia respond initially to vaccination, but no longer have detectable levantibody at 6 months. The Immunization Practices Advisory Committee of the Centers for Disease Control and Prevention (CDC) now recommends PPV23 for: All persons over the age of 2 years who are at substantially increased risk of developing pneumococcal infection and/or a serious complication of such an infection.

General categories included within these recommendations are those persons who: (1) are over the age of 65 years; (2) have anatomic or functional asplenia, CSF leak, diabetes mellitus, alcoholism, cirrhosis, chronic renal insufficiency, chronic

pulmonary

Recommendations regarding revaccination seem to be somewhat inconsistent because the committee advocates a single revaccination in persons over the age of 65 years as well as most others.

Since antibody levels decline and there is no anamnestic response, it seems more reasonable simply to recommend: Revaccination at 5 to 7 year intervals, particularly in adults over the age of 65 years, who will have a minimal local reaction.

Hyporesponsiveness (the failure to make antibody to a second vaccination when given soon after a first vaccination) is not seen 5 years after prior vaccination.

Revaccination every 5 years for persons who are at highest risk of recurring pneumococcal infection—those who have undergone splenectomy or have a CSF leak.

Infants and young children do not make antibody after vaccination with pure polysaccharide antigens. However, when pneumococcal capsular polysaccharides have been covalently conjugated to carrier proteins, the resulting antigens are recognized as T-cell dependent; they stimulate good antibody responses in children under the age of 2 years and induce immunologic memory.

In a field trial involving 38,000 infants and toddlers, vaccination with PCV7 produced a brilliant response, being followed by a 90% decrease in pneumococcal meningitis.

Widespread introduction of PCV7 in the pediatric population in 2000 decreased disease due to vaccine serotypes by ?90%, both in vaccinated and nonvaccinated subjects. The decrease in incidence in unvaccinated persons is called the “herd effect;” it occurs because PCV immunizes against colonization as well as against infection, and that effect reduces the prevalence of vaccine-type pneumococci in the population at large. An untoward result of widespread vaccination has been the appearance of new strains that are not contained in the vaccine; these are called replacement strains.

The principal one, type 19A, has become the predominant cause of pneumococcal disease in all age groups in the United States.